Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Regeneration of lost tail is of great importance to lizards. Anolis carolinensis, a green lizard, is capable of regenerating its tail efficiently after autotomy. Hence, it is considered as a model organism in regeneration study. A. carolinensis shed its tail in order to distract the predator’s attention and thus makes a way to escape. Restoring of the amputated tail takes several days and the mechanism is currently clearly understood. Although save its life, tail regeneration is associated with the impairment of several vital functions in Anoles. In addition, various differences have been observed between original and regenerated tail in terms of mechanism and structure. To date, very little work has been conducted on tail autotomy and regeneration at molecular and genetic level. The genes responsible for regeneration in anoles are identified recently. These genes are evolutionarily conserved through all tetrapod vertebrates. They are, however, in a state of ‘switched-off’ in other vertebrates including humans. Consequently, a throughout study of these so called ‘switched-off’ genes may provide a way of restoring lost organs in human, and thus could revolutionize the modern medical science.

Callus induction (CI) is the critical trait for the transformation of desirable genes in plants. A genome-wide association study (GWAS) analysis was conducted on the rice germplasm of 110 diverse indica rice accessions. Three tissue culture media, including B5, MS, and N6, were used for CI in those rice panels. Seven quantitative trait loci (QTLs) on chromosomes 2, 6, 7, and 11 were found to confer a CI percentage in these three media. For the B5 medium, one QTL (qCI-B5-Chr6) was identified on the rice chromosome 6. For the MS medium, two QTLs were identified on the rice chromosomes 2 and 6 (qCI-MS-Chr2 and qCI-MS-Chr6, respectively). For the N6 medium, four QTLs were identified on the rice chromosomes 6, 7, and 11 (qCI-N6-Chr6.1, qCI-N6-Chr6.2, qCI-N6-Chr7, and qCI-N6-Chr11, respectively). Fifty-five genes were identified within the haplotype blocks corresponding to these QTLs. Thirty-one genes showed haplotypes associated with different CI in those media. The qCI-B5-Chr6 was located in the same region as the qCI-N6-Chr6.2. The caleosin-related family protein was identified in this region. Analysis of the gene-based haplotype reveals the association of this gene with different CI in both B5 and N6 media, suggesting that the gene may play a critical role in the CI mechanism. Moreover, several genes, including the beta-tubulin, the zinc finger proteins, the RNP-1 domain-containing protein, and the Lysophosphatidic acid acyltransferase, were associated with different CI in the N6 media. Results from this study provide insight into the potential QTLs and candidate genes for callus induction in rice that will fulfill the understanding of the physiological and biochemical processes involved in callus formation, which is an essential tool in the molecular breeding of rice.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Small peptides (SPs), ranging from 5 to 100 amino acids, play integral roles in plants due to their diverse functions. Despite their low abundance and small molecular weight, SPs intricately regulate critical aspects of plant life, including cell division, growth, differentiation, flowering, fruiting, maturation, and stress responses. As vital mediators of intercellular signaling, SPs have garnered significant attention in plant biology research. This comprehensive review delves into SPs' structure, classification, and identification, providing a detailed understanding of their significance. Additionally, we summarize recent findings on the biological functions and signaling pathways of prominent SPs that regulate plant growth and development. The review also offers a forward-looking perspective on future research directions in peptide signaling pathways.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p <0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Purpose: The purpose of this study is to apply the Composite Radiographic Index modified (CRIm) in CBCT scans of patients with Medication related osteonecrosis of the jaws (MRONJ) in order to detect its validity, and corelate the radiologic findings with the clinical staging of the disease. Methods: This study included 43 patients with MRONJ diagnosis and CBCT scans performed in the School of Dentistry and approved by the Research Ethics Committee. Clinical staging for every patient (0-3) was provided according to AAOMS 2022 guidelines. In cases of patients with both jaws affected, each jaw was evaluated independently resulting to 52 CBCT scans. The 52 CBCT scans were assessed under standardized viewing conditions by 2 observers who evaluated independently the following 8 radiologic features: lytic changes, sclerosis, periosteal reaction, sequestration, non-healing extraction sockets and other findings (sinus implication, inferior alveolar canal involvement, jaw fracture). The CRIm index was constructed to assess the extent of osseous changes. The radiologic features were scored as absent (0), localized/single (1), extensive/multiple (2), yielding a theoretical range of 0–12. For statistical analysis Fisher’s exact test and Spearman’s correlation coefficient were performed. Results: A statistically significant association of clinical stage with lytic changes, sequestration and inferior alveolar canal involvement was found. Also, a statistically significant correlation of clinical stage with CRIm index classification was obtained. Conclusions: The CRIm index tends to increase as the clinical stages of MRONJ advance, suggesting a correlation between the clinical stage of MRONJ and the CRIm index.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

This study investigated the development of novel probiotic formulations specifically designed for rainbow trout aquaculture. The project evaluated the effects of two formulations containing potential probiotic strains isolated from rainbow trout itself. These effects were assessed on various parameters including growth performance, immune response, liver enzyme activity, gene expression related to immunity, and the composition of the bacterial gut microbiota in rainbow trout (Oncorhynchus mykiss). In a completely randomized experimental design, a total of 450 rainbow trout were randomly divided into 70-liter fiberglass tank. The study included six treatments of three replicates (n=18 tanks). Six dietary treatments were included (A) and (B) containing three strains of Pediococcus sp P15, Lactococcus lactis ml3, Weissella cibaria ml6 at two dosages (300 and 500 mg/kg), treatments (C) and (D) containing five strains of P. sp P15, L. lactis ml3, W. cibaria ml6, Enterococcus faecium E10 and Lactobacillus curvatus 13A at two dosages (300 and 500 mg/kg), a commercial probiotic (E) at 300 mg/kg, and a control group (F) without probiotics. Treatments of (A), (B) and (E) resulted in the highest final weights in compared to control group. Fish fed treatments (A) and (B) had the lowest FCR than other groups. Treatments (A) and (D) showed a significant increase in immunoglobulin M (IgM) concentration compared to other groups. The expression of tumor necrosis factor (TNF) was significantly lower in group (A) than the control. In contrast, the expression of interleukin 6 (IL6) and immunoglobulin T (IgT) was increased 4.4-fold and 41-fold, respectively, in group (A) compared to control group. Among the probiotic fed treatments, group (A) showed a significant higher number of lactic acid bacteria compared to other groups during the experiment. This study highlights the significant role of treatment (A) containing three strains of P. sp P15, L. lactis ml3, and W. cibaria ml6 at a dosage of 300 mg/kg as a potential probiotic product for the rainbow trout industry.

The global warming has caused poor grape skin coloration and reduced the production of high-quality berries. To overcome these problems, the effect of synephrine (Syn) on anthocyanin accumulation was investigated. Syn treatment above 1 mM increased anthocyanin content in cultured grape cells in a molecular-structure-specific and concentration-dependent manner, and increased only the anthocyanin without affecting the sugar/acid ratio in grape bunches. It increased the expression of genes linked to anthocyanin synthesis after 24 h of treatment, without affecting phytohormone levels. Syn treatment induced the expression of SOD3, elevating hydrogen peroxide (H2O2) production from 3 to 24 h after treatment in cultured cells. Subsequent increases in CAT and APX6 expression occurred, which encode H2O2-eliminating enzymes. In cultured grape cells, Syn and H2O2 treatments upregulated the H2O2-responsive gene Chit4 and the anthocyanin-biosynthesis-related genes mybA1 and UFGT 4 days after the treatments and promoted anthocyanin accumulation 7 days after the treatments. In berries, both treatments enhanced anthocyanin accumulation after 9 days. These results suggest that Syn promotes anthocyanin accumulation through the production of H2O2 without the upregulation of phytohormone biosynthesis. Syn treatment is expected to improve poor grape coloration and contribute to higher-quality fruit production.

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus while less common, tetanus is a serious disease following contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is this disease primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, malignant edema can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causing sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability.

Many types of banana (Musa spp.)—one of the most economically important horticultural crops—exist, and their ploidy (diploid, triploid, and tetraploid, usually) and genome types (containing A or/and B genome in most cases) differ. At present, observation and genome type detection are commonly used to identify banana germplasm resources. However, the former is tedious, while the latter cannot distinguish categories below genome types. It is therefore urgent that a simple and effective method for identifying banana germplasm resources is established. We sequenced and analyzed the ribosomal DNA internal transcribed spacer (ITS) sequences of 62 banana germplasm and found that the sequencing peaks, especially the 20 bp region near the 420 bp position (referred to as the “420 bp region”), exhibited relatively recognizable and repeatable polymorphism characteristics. Using the “420 bp region” as a marker, we were able to quickly distinguish bananas belonging to different genome type groups (comprising the AA, AB, AAA, ABB, AAB, ABBB, AAAB, and AAAA groups) or different subgroups in the same genome type group (for example, the Cavendish, Gros Michel, Red, Lakatan, and Ibota Bota subgroups in the AAA group; and the Pisang Raja, Plantain, Pome and Silk subgroups in the AAB group). Moreover, it appeared that Sanger sequencing of ITS could be used for identifying banana hybrid offspring. These results demonstrated that the banana ITS region contains rich genetic information that is useful for genotyping. In general, ITS sequencing simplifies the classification of banana germplasm resources and has potential application in several areas of Musa improvement.

Climate change, growing world population and increasing food demand require higher yields and adaptability of crops, including spring bread wheat. Modern plant breeding based on achievements of genetics has a significant impact on plant resistance to diseases, climate variability and other factors. Genome wide association studies (GWAS) is one of genetics tools for mining of genome loci associated with economically important traits. In the current study, we applied GWAS to reveal QTL for spike productivity and grain quality using a panel of spring varieties of Triticum aestivum L. bred in different decades of the last century in Russia and Germany. The study has enabled to find new genetic markers associated with grain yield and quality. Studying genetic basis of grain yield and quality by comparison of wheat varieties from different breeding periods, including landraces preserved as the source of valuable genetic diversity for breeding and genetic studies, makes it possible not only to understand selection processes in the past, but also to develop strategies for future breeding work.

High temperature stress affects tomato production both in tropical and sub-tropical environments worldwide. To explore genetic variation for heat tolerance in tomato, 329 transcontinental tomato varieties were evaluated at The Ministry of Municipality and Environment (MME) greenhouses near Doha, Qatar. Preliminary phenotypic analysis identified a diverse set of 71 hybrid and pure line tomato varieties for more detailed studies. The selected subset was examined in the greenhouse in a randomized complete block design under heat stress. The materials were phenotyped for fruit size, fruit weight, fruit hardness, fruit locules, fruit set (%), total soluble solids (TSS), and fruit yield. Significant phenotypic differences among genotypes were observed for all the traits assessed. To explore the genetic basis of variation among varieties the subset was genotyped using 104 SNP markers identified in previous heat tolerance genome wide association studies (GWAS). Nineteen QTL associated SNP markers could reliably select heat tolerant varieties in terms of better fruit yield, fruit set, and TSS. These markers are located on Chromosome 1, 5, 6, 8, 9, and 12. Interestingly, two clusters of markers on chromosome 6 were linked to significant effects on yield, fruit set, and TSS under high temperature. Some markers located within these QTL regions were also reported as associated with heat tolerance in other studies. Eighteen out of nineteen SNP markers were mapped within a gene body. Based on the phenotypic and the genotypic analysis, an elite set of five varieties was selected for approval for heat stress environments in Qatar. These findings have significance not only for Qatar, but they are also valuable for wider application at other locations worldwide. The 19 markers presented here could be adopted by breeders for marker-assisted selection (MAS) for heat tolerance.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

: This study focuses on optimizing chlorophyll extraction techniques and strategically placing leaf disks to enhance chlorophyll concentration in sesame (Sesamum indicum L.) leaves. Thirty sesame genotypes, categorized into light green (LG), middle green (MG), and deep green (DG) pigment groups based on leaf coloration, were selected from a larger pool of field-grown accessions. The investigation involved determining optimal SPAD value index measurements, quantifying pigment concentrations, exploring extraction solvents, and selecting suitable leaf disk positions. Significant variations in chlorophyll content were observed across genotypes, greenness categories, and leaf disk positions. The categorization of genotypes into DG, MG, and LG groups revealed a correlation between leaf appearance and chlorophyll content. The study highlighted a consistent relationship between carotenoids and chlorophyll, indicating their role in adaptation to warm environments. Examination of leaf disk positions revealed a significant chlorophyll gradient along the leaf blade, emphasizing the need for standardized protocols. Chlorophyll extraction experiments identified DMSO and 96% ethanol, particularly the later incubated for 10 minutes at 85°C, as effective choices. This recommendation considers factors like cost-effectiveness, time efficiency, safety, and environmental regulations, ensuring consistent and simplified extraction processes. For higher chlorophyll extraction, focusing on leaf tips and the 75% position along the sesame leaf blade is suggested, consistently yielding higher chlorophyll content. Our findings therefore, underscores insightful knowledge on chlorophyll gradients and encouraging for standardized protocols, that enabling researchers to refine experimental designs for precise and comparable chlorophyll measurements. Recommended solvent choices ensure reliable outcomes in plant physiology, ecology, and environmental studies.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

While genetic testing is becoming mainstream in the management of patients with potentially inherited cardiovascular disease, the prevalence of uncertain results severely limits its utility. One promising approach is to generate variant effect maps that report the function of all possible variants in a gene prospectively. The proactive clinical application of these maps is nascent, and it requires careful integration with current American College of Medical Genetics guidelines for variant interpretation. Here, we describe three pediatric cases of cardiac arrest or sudden cardiac death with variants of uncertain significance in calmodulin genes. We demonstrate the prospective clinical utility of a calmodulin variant effect map to inform variant interpretation, and therefore diagnosis and family care, in each case. This study was approved by the Stanford University and Vanderbilt University Medical Center IRBs. Consent was waived based on low risk of de-identified retrospective data collection per the IRB.

Fourteen Russian potato cultivars (cvs.) grown for three years in field plots of VIR (Northwestern region of the Russian Federation) were evaluated for productivity and a number of biochemical parameters of tubers. The 12 parameters that have been evaluated in tubers annually one month after harvesting and after cold storage (at 2 - 4°C) include the content of dry matter, starch, protein, ascorbic acid, carotenoids and β-carotene, anthocyanins, total sugars and monosaccharides (reducing sugars), phenolic compounds, as well as total acidity, and antioxidant activity. The cultivars differed significantly in productivity and biochemical composition of tubers. Dry matter content ranged from 16.40% in cv. ʻKumachʼ to 27.28% in ʻNayadaʼ, starch content ranged from 8.96 % in cvs. ʻFioletovyjʼ, ʻKumachʼ to 20.08% in ‘Sokur’, the total sugar content reached 2.46% in cv. ʻSiverskij’ whereas ‘Sokur’ has the smallest content of reducing sugars in post-harvest tubers. Protein content ranged from 1.02% to 2.77% with the highest accumulation in cv. ʻSokurʼ. Content of ascorbic acid (vitamin C) ranged from 6.3 mg/100 g FW in ʻKrasa Meŝeryʼ to 26.6 mg/100 g FW in cv. ʻKrasavchikʼ. Carotenoids content ranged from 0.157 mg/100 g FW in cv. ‘Nayada’ to 0.645 mg/100 g FW in cv. ʻGrandʼ. Content of anthocyanins in potato ranged from 1.04 mg/100g FW (not colored tubers of cv. ʻKrasa Meŝeryʼ) to 283.04 mg/100g FW (colored tubers of cv. ʻFioletovyiʼ). The nutritional value of tubers (content of dry matter, sugars, starch and protein) was determined to a greater extent (38-49%) by varietal characteristics, rather than by meteorological conditions in vegetation period. The content of vitamin C, carotenoids, protein and anthocyanins varied depending on the year. The highest content of dry matter, starch and carotenoids was noted in tubers harvested in 2019, marked by low temperatures and precipitation deficit in growing season. The conditions of 2020 with low temperatures and excess precipitation were the most favorable for anthocyanin’s accumulation in potato tubers while not for other biochemical parameters. Of the cultivars, ʻSokurʼ had the highest content of dry matter, protein and starch. Cv. ʻFioletovyiʼ had small starch content and high level of anthocyanins. Cv. ʻPlamyaʼ can be recommended for potato products manufacturing due to dry matter content above 20% and reducing sugars content 0.24%..

Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological and molecular investigations on thalassemias in Croatian population have been reported to date. This prospective study included 70 children with a presumptive diagnosis of thalassemia, and their 42 first-degree relatives. Molecular characterization was performed using direct sequencing and gap-PCR methods. We identified 46 (30 children and 16 first-degree relatives) β-thalassemia heterozygous carriers from 24 unrelated families, carrying eight different mutations and one hemoglobin variant. Five variants account for approximately 85% of all affected β-globin alleles: Hb Lepore-Boston-Washington (32,6%), HBB: c.93-21G>A (19,6%), HBB:c.315+1G>A (13,1%), HBB:c.92+1G>A (10,9%), and HBB:c.92+6T>C variant (8,7%). A need for more detailed genetic profiling of β-thalassemia carriers is emphasized since genetic modifiers can significantly impact their phenotype. Our study provides important new insights into the relevance of β-thalassemia heterozygosity in the pediatric clinical practice.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

Incidental findings (IFs) depicted in imaging tests during diagnostic evaluation of patients with cleft lip and/or palate (CL/P) can guide clinicians during treatment-planning procedures for effective, comprehensive cleft care. Evidence regarding IFs in different anatomical regions distant from the dentition are scarce. The aim of this study was to compare the prevalence of IFs in various anatomical areas between patients with non-syndromic CL/P and unaffected subjects. Orthopantomographs (OPT), lateral cephalometric (LC) radiographs and cone-beam computed tomography (CBCT) scans of 120 subjects (case group: n = 40, 18 females, age 14.5 ± 5.0 years; control group: n = 80, 36 females, age 14.6 ± 4.9 years) were examined and IFs were assessed by four observers. Significantly higher prevalence of IFs (p < 0.001) was reported in the case group (97.5%) compared with the control group (62.5%). The most prevalent location of IFs in the case group was the maxilla (92.5%), followed by the nasal cavity (75.8%) and the mandible (63.2%), while in the control group, the highest rates of IFs occurred in the maxilla (43.8%), mandible (41.3%) and temporomandibular joint (TMJ) (14.7%). No gender-dependent pattern for IF occurrence was detected overall. Orofacial clefts may affect the mandible. However, the reported IFs were limited compared to those in the maxilla. In conclusion, individuals with CL/P are more likely to present with a range of IFs than their unaffected peers. Understanding the association between CL/P and IFs is critical for successful interdisciplinary treatment, raising awareness of the potential need for future dental care for cleft patients, and managing extra-dental aberrations. A systematic assessment of diagnostic records is required to eliminate the risk of overlooking clinically significant IFs.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

A total of 27 microsatellites markers , scattered all over the genom of barley, were used for characterization,and diversity analysis in 33 barley (Hordeum vulgare L.) accessions and cultivars of Algeria.Over the 27 genetic loci studied, 110 alleles were identified with a mean of 4.1 alleles per locus and the average polymorphism information content (PIC) of 0.46,the marker Ebma0806 showed the greatest value of PIC with 0.83.Genetic diversity at 27 microsatellite loci varied from 0 to 0.84 (Mean=0.50) for 33 Algerian cultivars. The genetic distance among the cultivars ranged from 0.2 to 0.85. Cluster analysis and principal coordinate analysis (PCoA) based on the SSR data clearly differentiate the all genotypes studied.

Degnala is one of the main mycotoxicoses that affects buffaloes, and the fungus Fusarium spp. is the main causative agent. This disease is strongly related to the supply of rice straw to buffaloes and is considered endemic to regions where this crop is cultivated. Cases of the disease are concentrated in the winter, when conditions favour fungal growth in inadequately stored rice straw. Degnala is characterized by necrosis and gangrene of the extremities, including the tail, lower limbs, ears, tongue, muzzle and teats. The pelvic limbs are more affected than the thoracic limbs. A tortuous appearance of the tail is very common, and cracks or corneal loss of the hooves may occur, with exposure of the blades and even the bones. There is no diagnostic method for identifying the disease in animals other than the clinical and epidemiological criteria associated with fungal culture of rice straw samples. There is no treatment that neutralizes the effects of the toxins, and the treatment currently used is a palliative and supportive method consisting of pentasulfate solution, anti-Degnala liquid, 2% nitroglycerin ointment and broad-spectrum antibiotics for secondary infections. In addition, the management of drying straw and proper storage are essential for controlling this disease.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

Candidiasis is a significant fungal infection caused by various species of the genus Candida, posing health challenges to a wide range of animals, including Choloepus species (two-toed sloths). This review article aims to provide a comprehensive understanding of candidiasis in Choloepus sp., highlighting the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention strategies.The article begins by examining the causative agents, primarily focusing on Candida albicans, which is the most commonly implicated species in candidiasis. The epidemiological aspects are discussed, emphasizing the prevalence of candidiasis in wild and captive Choloepus populations and identifying predisposing factors such as immunosuppression, stress, poor nutrition, and environmental conditions. Pathogenesis is explored, detailing the mechanisms through which Candida species invade host tissues and evade immune responses. Clinical manifestations in Choloepus sp. are described, including oral thrush, cutaneous lesions, and gastrointestinal infections, and their impact on the health and behavior of affected individuals. Diagnostic methods, including culture techniques, histopathology, and molecular assays, are reviewed to highlight their roles in accurately identifying Candida infections. The article also covers treatment options, focusing on antifungal therapies and supportive care tailored to the unique physiology of Choloepus sp. Finally, prevention and management strategies are discussed, emphasizing the importance of maintaining optimal husbandry practices, regular health monitoring, and early intervention to reduce the incidence and impact of candidiasis in Choloepus populations. This review underscores the need for further research to enhance our understanding of candidiasis and improve health outcomes for these unique and vulnerable animals.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

In the course of our ongoing research targeting the identification of potential biocontrol agents from entomopathogenic fungi (EPF), we explored a solid-state rice fungal extract of Blackwellomyces roseostromatus BCC56290 derived from infected lepidopteran larvae. Chemical and biological prospections afforded four unprecedently reported natural products differentiated into one dimeric naphthopyran bioxanthracene ES-242 derivative (1) and three cyclodepsipeptides (2-4) in addition to two known cyclodepsipeptides, cardinalisamides B (5) and C (6). Chemical structures of the isolated compounds were elucidated through comprehensive 1D/2D NMR and HR-ESI-MS data together with comparisons to the reported literature. The absolute configuration of the isolated cyclodepsipeptide was determined using Marfey’s method. All isolated compounds were assessed for their antimicrobial, cytotoxic and nematicidal activities with some compounds revealed significant activities.

Serum biochemical indicators serve as vital proxies that reflect the physiological state and functions of different organs. The genetic parameters and molecular mechanisms underlying serum biochemical indicators of sheep (Ovis aries) have not been well understood. Therefore, the aim of the present study was to identify genetic architecture and genomic loci underlying ten serum biochemical indicators in sheep, including alanine transaminase, aspartate transferase, lactate dehydrogenase, cholesterol, glucose, phosphorus, calcium, creatinine, urea concentrations and total protein levels. We implemented genetic parameter estimations and GWAS for each trait in 422 Akkaraman lambs. Overall, low to moderate heritability estimates were found, in the range 0.14–0.55. Additionally, low to high genetic correlations were observed among traits. In total, 23 SNP loci were associated with serum biochemical indicators leading to 19 genes . These are SPTA1, MGST2, CACUL1, IGFBP7, PARD3, PHB1, SLC15A5, TRIM35, RGS6, NUP93, CNTNAP2, SLC7A11, B3GALT5, DPP10, HST2ST1, NRP1, LRP1B, MAP3K9, ENSOARG00020040484.1 as well as LOC101103187, LOC101117162, LOC105611309 and LOC101118029. To our knowledge, these data provide the first association between SPTA1 and serum cholesterol and between ENSOARG00020040484.1 and serum glucose. The current findings provide a comprehensive inventory of the relationships between serum biochemical parameters, genetic variants, and disease-relevant characteristics. This information may facilitate the identification of therapeutic targets and fluid biomarkers and establish a strong framework for comprehending the pathobiology of complex diseases as well as providing targets for sheep genetic improvement programmes.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age >18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p<0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p>0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of >99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

This study aimed to learn disturbance information to effectively control multiple small unmanned surface vehicles (USVs) for marine research purposes at sea. The learned disturbance information was used to investigate the control of multiple USV swarms based on the leading–following formation technique. Numerous studies have already been conducted on swarm control using drones in the air; however, there has been a paucity of studies on swarm control in the sea. Contrary to swarm control in aviation, the fluid density of the sea is high, and the environment is constantly changing; thus, a robot system would be significantly affected by disturbances. This ultimately influences the maintenance of swarm formations and the accomplishment of missions [1,2]. Therefore, it is difficult to control numerous moving objects while maintaining a formation at sea by using the existing aerial drone swarm control technology. To solve this problem, we learned a long short-term memory (LSTM) model with time-series marine environmental data to predict maritime disturbances. Thereafter, the model was applied to a mission-based position control algorithm of each USV constituting the swarm to design a marine unmanned floating vessel swarm control system that can be applied to various marine environments. Specifically, to effectively control numerous small USVs for marine research purposes, ocean currents are learned using the LSTM algorithm, and the predicted ocean currents are used to generate a swarm USV control system for USV formations. In this study, a control system model of several small USVs equipped with two rear thrusters and a front lateral thruster was designed. The LSTM algorithm was learned using the previous ocean current data, and the velocity of the following ocean currents was predicted. The predictions were then used as a system disturbance to determine the thrust of the controller. To measure ocean currents in the sea when each USV moves, the velocity, azimuth, and position (latitude, longitude) data from the GPS mounted on the USV were used to measure the velocity and direction of the hull's movement. Further, the flow rate was measured using a flow rate sensor on a small USV. The USV movement and position were controlled using an artificial neural network-PID (ANN-PID) controller. This study entailed a comparative analysis of the designed USV model results and those generated by the simulator, including the behavior control rule of the USV swarm and the path of the actual USV swarm at sea. It was verified that the effectiveness of the USV mathematical model and behavior control rules. By comparing the movement path of the swarm USV with and without the disturbance learning algorithm and ANN-PID control algorithm applied to the designed simulator, the position error and maintenance performance of the swarm formation were analyzed, and the application results were compared.

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Cancer is one of the leading causes of death, making timely diagnosis and prognosis very important. Utilization of AI (artificial intelligence) enables providers to organize and process patient data in a way that can lead to better overall outcomes. This review paper aims to look at the varying uses of AI for diagnosis and prognosis and clinical utility. PubMed and EBSCO databases were utilized for finding publications from January 1, 2013, to December 22, 2023. Articles were collected using key search terms such as “artificial intelligence” and “machine learning.” Included in the collection were studies of the application of AI in determining cancer diagnosis and prognosis using multi-omics data, radiomics, pathomics, clinical and laboratory data. The resulting 89 studies were categorized into eight sections based on the type of data utilized and then further subdivided into two subsections focusing on cancer diagnosis and prognosis, respectively. 8 studies integrated more than one form of omics, namely genomics, transcriptomics, epigenomics, and proteomics. Incorporating AI into cancer diagnosis and prognosis alongside omics and clinical data represents a significant advancement. Given the considerable potential of AI in this domain, ongoing prospective studies are essential to enhance algorithm interpretability and to ensure safe clinical integration.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

Mitochondria play a significant role in the functioning of the cell, acting both as an intracellular energy source and a signaling organelle. In the heart, mitochondria produce more than 95% of the ATP in addition to regulating the redox state, calcium homeostasis, apoptosis, and lipid synthesis. However, there is also evidence that mitochondria exist outside of cells where they have been observed to mediate cell-to-cell communication, repair, and participate in the immune response. Cardiometabolic disease (CMD) has a complex pathogenesis closely associated with mitochondrial dysregulation, inflammation, and metabolic abnormalities. Because of this metabolic interdependence between the myocardium and the intracellular mitochondria, circulating extracellular mitochondria (CEMI) are being identified as possible regulators of CMD. Outside of the cell, mitochondrial functions are determined by the mitochondrial form, either as whole functional structures (e.g., small extracellular mitochondria) or as mitochondrial components with or without membrane encapsulation. Here, we explore the different forms of CEMI, their role in CMD pathogenesis, their potential therapeutic utility in treating diseases, and their role as biomarkers.

Ovarian cancer (OC) represents a significant challenge in the realm of gynecological cancers, characterized by poor survival rates and complex etiology. In this review, we delve into the se-lected genetic, environmental, and hormonal factors underpinning OC development. We have reviewed scientific databases searching for ovarian cancer genetic and epigenetic factors. We have included studies based on their relevancy. As a result of exploring ovarian carcinogen-esis, this systematic review contains data collected from 126 various works. The role of prominent genetic players such as BRCA mutations, DNA repair mechanisms, un-derscores the intricate landscape of OC susceptibility. We explore Li-Fraumeni and Lynch syn-drome, which impart a heightened predisposition to OC development. Hormonal factors such as estrogen, progesterone, and androgens are also discussed. Environmental alterations, ranging from lifestyle influences on OC to microbiome dysbiosis and lifestyle factors such as obesity, al-cohol consumption, and physical activity intersect with genetic and epigenetic pathways, shaping the risk landscape for OC. Through a meticulous examination of current literature, this review provides a nuanced under-standing of the multifactorial nature of OC, emphasizing the need for holistic approaches to prevention, diagnosis, and treatment.

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

HPV51 belongs to group I high-risk HPV (hrHPV) genotypes with a high prevalence of infection in numerous epidemiological studies, although its occurrence varies across geographical regions. To better understand the presence of variants and genetic variation of HPV51, this study aimed to perform a phylogenetic analysis of the E6, E7 and L1 regions to detect the hrHPV variants circulating in women referred to colposcopy in two different Italian regions (Lombardy and Sardinia). Cervical samples were tested using Anyplex™ II HPV HR Detection. HPV51 positive samples were further analysed using previously described PCR protocols to obtain sequences of E6, E7 and L1. A positivity rate for HPV51 of 7.4% (26/351) and 13.6% (11/81) was found in Lombardy and Sardinia, respectively. The majority (34 out of 35) of the analyzed sequences clustered into the A lineage and only one sequence was grouped into B lineage. L1 capsid gene showed the presence of different mutations but none under positive selective pressure. Three nucleotide polymorphisms T6311G, A6312T and G6313A related to the two aminoacidic mutations V264G and G265S were found among all analysed sequences. This study contributes to implement data regarding the molecular epidemiology of HPV but additional analysis on a larger number of sequences is necessary to better understand the role of HPV variants in cervical lesions development.

The study findings revealed significant variability in various wood properties among different genetic families, although the static modulus of elasticity did not exhibit significant differences between the chosen genetic families. All measured wood properties decreased from the bottom to the top of the model trees. Wood hardness displayed a moderately negative correlation with wood density and weak correlations with MOE and MOR. Given the weak correlations between wood hardness and other wood mechanical properties, it is suggested that the MOEdyn would be a more suitable trait for genetic studies.

Objective: The aim of our study was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Results: There was a statistically significant age difference between the two study periods, both by the average age of patients and by age group. The mean difference was 32 years before the pan-demic and 35 years during the pandemic (p-value >0.05). The majority of patients presenting for investigations before and during the pandemic were in the 30-39-year-old age group (31.95%, respectively; 34.2% (p-value = 0.003). The biggest patient loss ratio identified by age group was in the 50–59 years: 14,53% in the pre-pandemic period and 9,1% in the pandemic period. In the pan-demic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the prepandemic period, with an increase in more severe lesions in the pandemic period, has a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusion: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervicorrhagia as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

Light is a crucial environmental factor that influences the phenotypic development of plants. Despite extensive studies on the physiological, biochemical, and molecular mechanisms of the impact of light on phenotypes, genetic investigations regarding light-induced transgenerational plasticity in Arabidopsis thaliana remain incomplete. In this study, we used Arabidopsis thaliana as the material, then gathered phenotypic data regarding leaf number and plant height under high- and low-light conditions from two generations. In addition to the developed genotype data, a functional mapping model was used to locate a series of significant SNPs. Under low-light conditions, a noticeable adaptive change in the phenotype of leaf number in the second generation suggests the presence of transgenerational genetic effects in Arabidopsis thaliana under environmental stress. Under different lighting treatments, 33 and 13 significant genes associated with transgenerational inheritance were identified, respectively. These genes are largely involved in signal transduction, technical hormone pathways, light responses, and the regulation of organ development. Notably, genes identified under high-light conditions more significantly influence plant development, whereas those identified under low-light conditions focus more on responding to external environmental stimuli.

(1)Background: Fascioliasis is considered a neglected tropical disease affecting an estimated 17 million people in more than 70 countries worldwide. The highest prevalence of human fascioliasis is found in regions where livestock farming and consumption of raw or undercooked freshwater plants are common, such as parts of Africa, Asia, Europe, and Latin America. It is responsible for over 90,000 disability-adjusted years of life due to associated abdominal complications. We conducted a study to investigate the prevalence of human fascioliasis through a systematic review and meta-analysis of all available literature in Sun-Saharan Africa.(2). Methods: We screened a total of 126 publications using pubmed online search engine databases; Web of Science and CAB for articles published within a 20-year period between 2000 and 2022. We used a comprehensive search method using a combination of terms, parasite and disease names. The initial search resulted in a screening of articles by title, abstracts and full texts. The relevant information on the prevalence of human fascioliasis in Africa was extracted. Of the 126 publications, 33 articles were selected for meta-analysis. The essential information required was extracted from these documents and determined through statistical analysis in Microsoft Excel for calculating the prevalence of human fascioliasis in sub-Saharan Africa. The variance of each study was assessed using a bimodal distribution and heterogeneity assessment using a I2 index. Analysis was performed using random effects models.(3)Results: A total of 271 articles were searched through the database search and 33 articles were eligible studies that provided qualitative information on the prevalence of human fascioliasis in Africa. These make up 12.17% (n=33). The pooled prevalence estimates for human fascioliasis are 0.032% (IVhet PPE: 0.032% (95%CI 1.4-6.53). The highest prevalence rate was observed in Egypt with a prevalence of 100%. The prevalence of human fascioliasis is very high in some sub-Saharan countries, partly due to neglect of diagnostics, demonstrating the bias of available information for decision-making in human fascioliasis across Africa, given the spatial presence, scarcity and incompleteness are region.(4)Conclusions: The prevalence of Human fascioliasis is very high in some Sub-Saharan Countries partly due to neglect in diagnostics. This presents how highly focal with spatial occurrences, scarcity and patchy the available information for decision making is on Human fascioliasis across the Sub-Saharan African region.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Quite a number of cottonseed varieties are existed. The seeds of each variety produce a different amount of gossypol as a natural toxic compound. The increased interest in this natural product and its toxic effects were enhanced the demand for establishing simple silica-gel-based methods for its isolation, purification, and characterization. Historically, silica gel plays a significant role in isolation and purification of many different natural products. Silica gel is variants and can intro-duce a lab, simple tool for tracking a compound in certain plants during its purification process. In this study, gossypol was isolated and purified in the form of yellow crystals as gossypol acetic ac-id. Several methods and tools were used for its characterization including TLC, preparative TLC, silica gel column, UV/IR spectrophotometer and HPLC (Robust spherical silica gel). A compara-tive study between its amounts in both Egyptian and Chinese varieties were performed. Under the experimental condition, the Egyptian cottonseeds contain 8.705 gm/kg, while the Chinese contains 5.395 gm/kg. Thin Layer Chromatography (TLC) had been flourished the science of the phytochemistry and still popular till nowadays and is recommended for fast, accurate, and inex-pensive evaluation and quantification of gossypol. It is recommended to isolate and purify gossy-pol as gossypol acetic acid using optimized combined methods used in this study. Using Silica gel different protocols will assist and facilitate the parallel comparison and save the compact column from any unexpected contaminants during the purification steps. During each step the silica gel itself could be simply removed by paper filtration.

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by Real-Time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The releasing of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. Results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

The implementation of systems condition monitoring is of utmost importance in ensuring effective maintenance, optimal efficiency, and adherence to established design criteria. This research presents a novel and economically efficient Digital Twin Model (DTM) designed for the purpose of Live Condition Monitoring (LCM) and Predictive Lifecycles. This study discusses the enhancement of DTs modelling by decreasing the number of dimensions from five to three: Physical, Digital, and Connection entities. The resulting model exhibits a notable improvement in accuracy and efficiency. The suggested Dynamic Time Model (DTM) enhances the empirical pre-set average load for both simulation and experimentation by 35.7%, which is equivalent to a 1.6-fold increase. The DTM demonstrates a significant enhancement in the empirical predefined average lifecycles of the system, as shown in the real-life case study. Specifically, the DTM achieves a 12-fold improvement compared to the simulated results and a nine-fold improvement compared to the experimental findings. The suggested Dynamic Time Management (DTM) demonstrates a significant enhancement in the average lifecycles of the system, with a 19.7% improvement (equivalent to 1.2 times greater) compared to the wireless DTM results obtained through the application of the real system load. The suggested Dynamic Time Warping (DTW) method's accuracy and efficiency are shown via a practical case study using the suspension system of a Peugeot 3008 vehicle.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Abrus precatorius is a medicinal herb originated from Southeast Asia and native to India. The Hindustani centre of origin was found to possess lot of variability especially with respect to seed color. However, no previous researchers have focused on studying the variability by including the entire variability of the region. A total of 99 accessions were analyzed for its biochemical components like moisture content, total phenols, antioxidants, ash content, protein content, total monomeric anthocyanin and flavonols. Principal component analysis (PCA) shown that first three components viz., seed color, phenols and antioxidants are major principal components that contribute to 80.86% of total variability in the germplasm. The dendrogram constructed based on the biochemical data and by using the software Darwin version 6.0. formed three main clusters i.e. cluster 1, cluster 2 and cluster 3 which contain 55 accessions, 40 accessions and 1 accession respectively. Seed color was found to be the main criteria based on which the Abrus accessions were grouped. Accessions from different clusters also differ for their mean phytochemical constituents. Germplasm curators / plant breeders can select such elite genotypes and utilize them in crop improvement programmes.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC) leading to premature death. Multiple evidences suggest a permissive tumor micro-environment (TME) as driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into 4 groups based on their occurrence (first onset or recurrences) and grading according to their clinical-histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analysed. Five RDEB patients experienced an unfavorable course af-ter the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 pa-tients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment, and an increased proportion of neutrophil extracellular traps (NET). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focus on pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by pfhrp2. Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69 % in the study area. About 85% of the major epitopes targeted by Monoclonal antibodies (MAbs) in RDT were identified. Our study suggests that the extensive sequence variation in the pfhrp2 could contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.

Amid the swift progression of the global automobile industry, the aspiration for lightweight vehicle design has surfaced as a crucial approach to boost fuel efficiency and curtail environmental impact. The objective of this study revolves around achieving holistic optimization of vehicle structure via detailed scrutiny of vehicle process characteristics, amalgamated with a Back Propagation neural network (BPNN) optimized by a genetic algorithm (GA) and a topology optimization (TO) method.The process initiates with an examination of the vehicle's technical characteristics, succeeded by an optimization protocol that couples GA with BPNN. This exhaustive optimization procedure derives the best-fit values of design parameters and identifies the globally optimal lightweight design approach. Subsequently, a comprehensive structural optimization is actualized by modifying the topological distribution of the structure.A simulation experiment of the conceptual car body beam skeleton is conducted as a conclusive step, and the anti-collision capacity of the car body beam skeleton is assessed by measuring deformation intrusion. The findings reveal that in the vehicle topology optimization, a comparative analysis of pre and post-optimization results indicates an improved topological density across diverse sections. The topological density of the vehicle's frontal structure escalates from 0.75 to 0.8. Following optimization, the stiffness assessment records a marginal increase (within the range of 0.02–0.05), implying that the lightweight design does not compromise the general rigidity of the structure.The optimized body structure manifests superior crashworthiness in the crash test: the deformation intrusion diminishes by 27% in front-end collisions. In side impacts, the deformation and intrusion at critical points are reduced by 13.15% to 10% respectively. The comprehensive method proposed herein proves to be an efficient strategy to actualize the lightweight design of vehicles.

Sugarcane mosaic virus (SCMV) and sugarcane streak mosaic virus (SCSMV) are the primary viruses responsible for mosaic diseases in sugarcane. In this study, the mosaic viruses SCMV and SCSMV with the involvement of sorghum mosaic virus (SrMV) were surveyed from eight commercial sugarcane cultivars grown in fields at four locations in East Java, Indonesia. Sugarcane leaves with mosaic symptoms were assessed for disease incidence and severity, and symptomatic leaves were collected for analysis. The incidence and severity of mosaic symptoms were the highest in the PS881 and NX04 cultivars grown in Kediri compared to the other cultivars. RT-PCR analysis showed that SCSMV was present in all sugarcane cultivars and locations. Interestingly, double mixed infections with SCMV were found in PS881, PS882, and Cening, whereas triple mixed infections with SrMV were found in the PS881 cultivar. Phylogenetic analysis grouped SCSMV, SCMV, and SrMV together with isolates from Thailand (KP987832.1), Florida, USA (MT725538.1), and Agentina (EU189037.1). The expression of ascorbate peroxidase gene (Apx) was increased in the virus-infected sugarcane cultivars and prominently elevated in the triple mixed infection of PS881 cultivars. However, the catalase gene (Cat) was slightly upregulated in the mixed infection group. The chlorophyll content was significantly reduced in the leaves of PS58, PS881, PS882, NX04, and HW Merah, in parallel with the expression of the photosystem I gene (PsaA). The expression of photosynthetic genes, such as ribulose-1,5 bisphosphate carboxylase small sub-unit (RbcS), phosphoenolpyruvate carboxylase (Pepc), sucrose-phosphate synthase (Sps1), and PsaA, was significantly reduced and almost depleted in the triple mixed infection of PS881, except for Pepc expression, which remained approximately half of that in the control healthy sugarcane. The decrease in photosynthetic activity was confirmed by the decrease in ribulose-1,5 bisphosphate carboxylase (Rubisco) and PEPC proteins, as detected by immunoblot analysis. The decrease in photosynthetic parameters indicated that the mosaic viral infection substantially reduced the growth and yield of sugarcane.

Properties of time domain parameters of the vibration signal have been extensively studied for the fault diagnosis of rolling element bearings (REB). Parameters like kurtosis and Envelope Harmonic-to-Noise Ratio are most widely applied in this field and some important progress has been made. However, since only one-sided information is contained in these parameters respectively, problems still exist in practice when the signals collected are of complicated structure and/or contaminated by strong background noises. A new parameter, named Shock pulse index (SPI), is proposed in this paper. It integrates the mutual advantage of both parameters above and can help effectively identify fault related impulse components under the interference of strong background noises, unrelated harmonic components and random impulses. The SPI optimizes the parameters of Maximum Correlated Kurtosis Deconvolution (MCKD), which is used to filter the signals under consideration. Finally, the interested transient information contained in the filtered signal can be highlighted through demodulation with Teager Energy Operator (TEO). Fault related impulse components can therefore be extracted accurately. Simulations and experiment analyses verify the effectiveness and correctness of the SPI.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Plants are subjected to abiotic stresses throughout their developmental period. Abiotic stresses include drought, salt, heat, cold, heavy metals, nutritional element and oxidative stresses. Improving plant response to various environmental stresses is critical for plant survival and perpetuation. The WRKY transcription factors have special structure (WRKY structural domains), which enable WRKY transcription factors to have different transcriptional regulatory functions. The WRKY transcription factors can not only regulate abiotic stresses response and plant growth and development by regulating phytohormone signalling pathways, but also promote or suppress the expression of downstream genes by binding to the W-box [TGACCA/TGACCT] in the promoters of their target genes. In addition, WRKY transcription factors not only interact with other families of transcription factors to regulate plant defence responses in abiotic stresses, but also self-regulate by recognizing and binding to W-boxes in their own target genes to regulate their defence responses to abiotic stresses. However, in recent years, research reviews on the regulatory roles of WRKY transcription factors in higher plants are scarce and shallow. In this review, we focus on the structure and classification of WRKY transcription factors, as well as the identification of their downstream target genes and molecular mechanisms involved in the response to abiotic stresses, which can improve the tolerance ability of plants in abiotic stress and we also look forward to their future research directions, with a view to providing theoretical support for the genetic improvement of crop abiotic stresses tolerance.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

Cassava (Manihot esculenta Crantz), domesticated in the Amazonian region of South America, presents an important diversity in Ecuador, where it is a main staple food; however, only few Ecuadorian cassava accessions have been included in international molecular assessments. The purpose of this study was to apply suitable cassava mi-crosatellites to characterize the genetic variability of the Ecuadorian cassava collection composed mainly of local landraces from the Coast, Andes and Amazonia regions. The use of microsatellite markers allowed the determination of the genetic diversity of the collection. Seven selected SSR primers, permitted to identify homozygous and hetero-zygous materials within the cassava collection of 133 accessions. The loci presented an average genetic diversity value of 0.7 and an average PIC value of 0.67, which is con-sidered high. Low number of duplicates (8.8%) were identified in the Ecuadorian col-lection which is not fully duplicated at CIAT. Currently, a wide range of cassava diver-sity is still cultivated in multi-crop agro-ecosystem, mainly in the Coast and Amazo-nian regions. Especially in the Amazonian region, due to important cultural uses of cassava by local ethnic communities, more in depth studies in the region could unveil the genetic diversity present in situ today.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. The study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had a significantly higher cytoplasmic E-cadherin score (P=0.043), they were significantly less differentiated (P=0.007), more advanced (P=0.005), and predominately affected right colon (P=0.030) in comparison to non-mucinous tumors. Epithelial tumors were significantly better differentiated (P=0.034) and with less prominent tumor budding (P < 0.001) than mesenchymal tumors. The process of EMT appears to be more prominent in tumors of younger patients regardless of mucinous histology. EMT status may represent a useful prognostic tool in early-onset CRC.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p&lt;0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle, a respiratory form, and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus whereas the gastroenteric form causes neonatal diarrhea or calf scour in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscores the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. Research data so far have shown that the viral structure or strain is not a determinant of tissue tropism and clinical form of the disease. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. The virus is classified under Coronaviridae family, Betacoronavirus genus and Betacorovirus 1 species. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have also been used increasingly in recent years for the detection and identification of BCoV. Loop-mediated isothermal amplification, helicase-dependent amplification, recombinase polymerase amplification, and multienzyme isothermal rapid amplification are some examples of the isothermal amplification assays for used BCoV. Point-of-care testing has gained some popularity recently as they can offer user-friendly testing on the farm (barn-side). The present study reviewed literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are underinvestigated. Here we performed the analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis, molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Due to the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids, independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

Group A rotaviruses (RVA) have been identified as the leading cause of neonatal calf diarrhea (NCD) In Yunnan, China, despite the limited documentation on this issue within the country. Given the significant impact on animal health and welfare, further attention is warranted to comprehend the prevalence and epidemiology of this disease. In this study, we isolated RVA strains from NCD clinical samples to support RVA epidemic study and further disease control in Yunnan. Material and Methods: Ten fecal samples were obtained from calves with a single episode of neonate calf diarrhea from a farmer during a severe NCD outbreak. For the diagnosis of Group A rotavirus (RVA) infection, fecal reverse transcription-polymerase chain reaction (RT-PCR) was employed as the primary method. Subsequently, RVA isolation was conducted on MA104 cells, with inoculates being pretreated with trypsin TPCK to enhance viral infectivity. The isolated RVA strain was further confirmed through RT-PCR and immunofluorescence assay. Results: RVA virus was isolated from clinical samples following six passages depended on trypsin treatment of inoculates. The sign of CPE detected consisted of increased cell granularity, obscure cell boundaries, cell rounding, and eventual degeneration and detachment of cells. Analysis of sequencing revealed that field isolates was of group A serotype. Phylogenetic analysis based on the ORF sequences of the VP4 and VP7 sequences segments indicated that the isolate was classified as the P[1] genotype. VP4 gene of strain YN-1 shares 75.2%-99.7% nucleotide identity of and 81.6%–99.7% amino acid identity with the complete VP4 sequences of the P[1]. The complete VP7 gene of YN-1 is 981 nucleotide long and encode 326 amino acids. The RotaC v2.0 analysis classified the sequence as the G8 genotype. The VP7 gene of strain YN-1 shares 88.5%-97.7% nucleotide identity and 94.2%-99.1% amino acid identity. Conclusion: This is the first study in China which reports the circulation of Group A NCD on cattle farms in the field. Our study constitutes a crucial and a necessary step allowing preventive and veterinary medicine to support RVA disease controls in Yunnan province, China.