HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Mobile health technologies enable continuous, quantitative assessment of mobility and gait in real-world environments, facilitating early diagnosis of gait disorders, disease progression monitoring, and prediction of adverse events like falls. Traditionally, mobile gait assessment predominantly relied on body-fixed sensors positioned at the feet or lower trunk. Here, we investigate the potential of an algorithm utilizing an ear-worn motion sensor for spatiotemporal segmentation of gait patterns. We collected 3D acceleration profiles from the ear-worn sensor during varied walking speeds in 53 healthy adults. Temporal convolutional networks were trained to detect stepping sequences and predict spatial relations between steps. The resulting algorithm, mEar, accurately detects initial and final ground contacts (F1 score of 99% and 91%, respectively). It enables determination of temporal and spatial gait cycle characteristics (among others stride time and stride length) with good to excellent validity at a precision sufficient to monitor clinically relevant changes in walking speed, stride-to-stride variability, and side asymmetry. This study highlights the ear as a viable site for monitoring gait and proposes its potential integration with in-ear vital sign monitoring. Such integration offers a practical approach to comprehensive health monitoring and telemedical applications, by integrating multiple sensors in a single anatomical location.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

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.

Background: Diagnostic accuracy of Parkinson’s disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research aspect. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with >10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen’s d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. Effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. PD cohort characteristics (sex, age, disease duration, UPDRS, H&Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. Standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future.

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.

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.

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.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

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.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.

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.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

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.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

The utilization of electroporation for delivering the CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In our study，This research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. The investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.

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.

Background/Objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts standard breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention for OSA are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, age at the time of PSG, and PSG outcomes in children; Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records on the age at referral for PSG and at the time of its execution, the waiting time for PSG, diagnosis (primary snoring, mild, moderate, and severe OSA), history of snoring and apnoea, medications taken, surgical interventions, passive smoke exposure, and allergies. The records also included the Pediatric Sleep Questionnaire (PSQ); Results: The mean age at referral for PSG was 5.2 (2.8) years, the waiting time for PSG was 5.2 (5.0) months, and the age at the time of PSG was 5.6 (2.8) years. Children with a shorter history of OSA (≤12 months) underwent PSG at an earlier age (4.9 (2.7) years) compared to those with a more extended history (6.0 (2.7) years; p=0.006). A younger age at referral for PSG was associated with a lower PSQ score (r=0.167; p=0.015), a shorter history of apnoea (r=0.216; p=0.003) and snoring (r=0.187; p=0.023), but also with greater OSA severity, expressed as oxygen desaturation index (r=-0.152; p=0.026). In the correlation analysis, the waiting time for PSG, adjusted for age at referral, was longer in children with a prolonged history of apnoea (r=0.195; p=0.023) and snoring (r=0.259; p=0.002) but with a lower PSQ score (r=-0.172; p=0.045); Conclusions: Some children receive delayed treatment, increasing the risk of long-term complications. In evaluating children with suspected OSA, the duration of symptoms and the PSQ score at referral emerge as crucial factors that should be considered to optimise prioritisation for PSG access.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Determining the estrous cycle stages in mice is essential for optimizing breeding strategies, synchronizing experimental time lines, and facilitating studies in behavior, drug testing, and genetics. It is critical for reducing the production of genetically unmodified offspring in the generation and investigation of genetically modified animal models. An accurate detection of the estrus cycle is particularly relevant in the context of the 3Rs—Replacement, Reduction and Refinement. The estrous cycle, encompassing the reproductive phases of mice, is key to refining experimental designs and addressing ethical issues related to the use of animals in research. This study presents results from two independent laboratories on the efficacy of the Mouse Estrus Detector (MED) from Elmi Ltd. (Latvia) for the accurate determination of the estrus phase. The female mice of five strains/stocks (CD1, FVB/N, C57Bl6/J, B6D2F1, and Swiss) were used. The results showed that the MEDProTM is a low -traumatic, simple, rapid and painless method of estrus detection that supports the principles of the 3Rs. The use of the MEDProTM for estrus detection in mice caused minimal stress, enhanced mating efficiency, facilitated an increase in the number of embryos for the in vitro fertilization and allowed the production of the desired number of foster animals.

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.

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.

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.

Sensory processing challenges are crucial yet often neglected aspects in the care of children with neurodevelopmental disorders and genetic conditions. They represent a key area of interest in neuroscience, as they significantly impact children's daily functioning and quality of life. This observational study examines the characteristics of these challenges in a group of 614 children, aged 3 to 14 years and 11 months, divided into three groups: 183 with neurodevelopmental disorders (Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, developmental delays, learning disorders), 89 with genetic conditions (22q11.2 Deletion Syndrome, Williams Syndrome, Pseudohypoparathyroidism), and 342 controls. Sensory processing was assessed using the Sensory Profile 2 (SP2). Results indicated that children with neurodevelopmental disorders and genetic conditions exhibited significant sensory processing difficulties compared to controls. The SP2 identified sensory challenges across different sensory systems, with varying configurations depending on the diagnosis. Children with neurodevelopmental disorders and genetic conditions show marked sensory processing challenges impacting daily lives and well-being. These findings highlight the importance of early identification and tailored evidence-based interventions to address these specific sensory processing issues. Further research should explore the long-term impact of these interventions in these different populations and their integration into broader therapeutic programs.

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.

Due to its intriguing applications across a wide range of industries, nanotechnology is generating a lot of interest globally. Titanium dioxide (TiO2) nanoparticles are one type of nanoparticle (NP) that is commonly utilised in everyday use and can be produced using a variety of physical, chemical, and environmentally friendly techniques. Green synthesis is an economical, environmentally benign, and non-toxic method of synthesising NPs. Under normal circumstances, the application of TiO2 greatly enhanced the plants' shoot length, leaf area, and root dry weight. These growth-promoting factors coincided with elevated proline, soluble sugar, and chlorophyll B levels as well as improved antioxidant enzyme activity. Thus, higher levels of proline and other metabolites played a role in osmo-protection, while increased antioxidant enzyme activities helped to explain the observed decrease in hydrogen peroxide and malondialdehyde contents. Taken together, these factors significantly improved plant growth under salinity. TiO2 nanoparticles have demonstrated efficacy in treating contaminated water and have been shown to positively impact plant physiology, particularly in response to abiotic stresses. However, the reaction to these nanoparticles varies depending on characteristics such as metal species, type, size, shape, dose, duration of exposure, and other variables. One of the most popular nanomaterials in customer goods, agricultural, and energy industries is TiO2 NPs. Therefore, harm to ecosystems and living things will unavoidably result from high demand and widespread usage. Gaining more knowledge about the toxicity of TiO2 NP to living things could help with risk assessments and safe handling procedures for these nanoparticles. The synthesis of titanium oxide, its many uses, the toxicity of titanium dioxide nanoparticles, and their mode of toxicity are all summarised in this paper.

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.

African yam bean (Sphenostylis stenocarpa Hochst, Ex. A. Rich. Harms) is an important grain legume in sub-Saharan Africa because of its nutritional value and adaptability to various agroecological zones. To foster the varietal development of improved African yam bean (AYB) genotypes with economic traits, it is necessary to validate parental polymorphism for key markers in selecting progenies from crosses between desired parents. The study aims to analyze the genetic fidelity between parents and F1 progenies in African yam bean through putative cowpea Simple sequence repeat (SSR) markers. Hence, a total of seventy-seven progenies were derived from four sets of biparental crossings using drought-susceptible (TSs-96, TSs-363, and TSs-274) and drought-tolerant (TSs-417, TSs-111, and TSs-78) AYB accessions. These were validated using 120 cowpea primers targeting SSR under optimal PCR conditions, and the size of the PCR-amplified DNA fragments was checked using gel electrophoresis. Twenty primers exhibited polymorphism in the parental lines, while ten displayed higher levels of the same polymorphism. The average polymorphism level for the surveyed SSR markers was 0.36. Given these findings, our study demonstrates that cowpea SSR markers are a reliable method for regular testing and clear identification of AYB crosses, indicating potential AYB improvements.

: 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.

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.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

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.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

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&gt;A (19,6%), HBB:c.315+1G&gt;A (13,1%), HBB:c.92+1G&gt;A (10,9%), and HBB:c.92+6T&gt;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.

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 immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

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.

Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

In patients with schizophrenia, metabolic syndrome is associated with cognitive impairments. We carried out a second analysis of data from a longitudinal trial to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) over the first 6-month antipsychotic treatment. Baseline and 6-month endpoint measurements were taken for both cognitive function and body weight. Linear and logistic regression analyses were applied to investigate the bidirectional relationship between weight gain and cognitive function. Clinically relevant weight gain (CRW) was defined as an increase in body weight ex-ceeding 7%. The final analysis included 337 participants. Lower baseline scores in processing speed (OR=0.837, p=0.007), working memory and attention (OR=0.889, p=0.043), and executive function (OR=0.863, p=0.006) domains were significantly associated with CRW at the 6-month endpoint. After adjusting for confounders, CRW was found to be associated with improvement in the Brief Visuospatial Memory Test (p=0.036). The findings suggest that patients with lower baseline cognitive performance experienced more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cog-nitive function in patients with first-episode schizophrenia.

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.

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.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Exome sequencing has been commonly used in rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) to search for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to heritability in complex clinical traits. We have conducted a systematic review to find evidence supporting the use of EP strategies to search for rare variants in genetic studies of complex diseases, to highlight the contribution of rare variation to the genetic structure of multiallelic conditions. After performing the quality assessment of the retrieved records, we selected 19 genetic studies considering EP to demonstrate genetic association. All the studies successfully identified several rare variants, de novo mutations and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach in patients with an early onset of the disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments are conducted according to clinical symptoms. Objective and biological validation are lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers in-cluding brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interfer-on-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.

Cellular senescence is a permanent condition of cell cycle arrest caused by a progressive shorten-ing of telomeres defined as replicative senescence. Stem cells may also undergo an accelerated se-nescence response, distinct from telomere shortening, known as premature senescence as a re-sponse to different stress agents. Various treatment protocols have been developed based on epi-genetic changes in cells throughout senescence, using different drugs and antioxidants, senolytic vaccines, or reprogramming of somatic senescent cells using Yamanaka factors. Even with all the recent advancements, it is still unknown how different epigenetic modifications interact with ge-netic profile and how other factors such as microbiota physiological conditions, psychological states and diet influence the interaction between genetic and epigenetic pathways. The aim of this review is to highlight the new epigenetic modifications that are involved in stem cell senescence. Here, we review recent senescence-related epigenetic alterations such as DNA methylation, chro-matin remodeling, histone modification, RNA modification, and non-coding RNA regulation outlining new possible targets for therapy of aging-related diseases. The advantages and disad-vantages of the animal models used in the study of cellular senescence are also briefly presented.

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.

Background and Aims: Obesity is a pervasive health issue in children. It affects multiple systems in the body including the gastrointestinal tract. Research on obesity-related gastrointestinal diseases has focused mostly on hepatobiliary disorders. However, non-hepatic gastrointestinal diseases such as gastroesophageal reflux, constipation, and functional abdominal pain, though common and debilitating, have not been highlighted in the context of obesity. These entities can downgrade the already compromised lifestyle of obese children. Some of these disorders are more difficult to treat in these children compared to their peers with normal body mass index. Method: We reviewed the available literature on the association between obesity and these three common gastrointestinal disorders. Results: - There appears to be a strong correlation between childhood obesity and constipation and gastroesophageal reflux, and a probable correlation with functional abdominal pain. Conclusion: We suggest that given the available literature, weight management should be an integral part of the management of gastroesophageal reflux, constipation, and functional abdominal pain in obese children. This gains relevance especially because of the recent availability of medications for the treatment of obesity in children.

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.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome," linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

Myeloperoxidase (MPO) is an enzyme that contains a heme group, found mostly in neutrophils and in small amounts in monocytes and plays a major role in their anti-microbial activity. However, excessive levels of MPO have been linked to various disorders and identified as a major cause of tissue destruction. Inhibiting its activity can reduce the severity and extent of tissue damage. Over activity of MPO during chronic inflammation has been shown to be involved in tumorigenesis by inducing a hyper-mutagenic environment through oxidant interaction with DNA, causing DNA modification. Vascular endothelium is one of the most important targets of MPO and high levels have been associated with increased rates of cardiomyopathy, ischemic stroke, heart failure, myocardial infarction, and atrial fibrillation. Therefore, it may be considered a therapeutic target in the treatment of cardiovascular disorders. MPO also participates in the pathogenesis of neurodegenerative diseases. For example, an increase in MPO levels has been observed in the brain tissue of patients with Alzheimer's, Multiple sclerosis (MS), and Parkinson's diseases. In Alzheimer's disease, active MPO is mostly found in the location of beta amyloids and microglia. Therefore, targeting MPO may be a potential treatment and prevention strategy for neurological disorders. This review will discuss MPO's physiological and pathological role in cancer, cardiovascular, and neurological disorders.

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.

In the contemporary accelerated pace of life, emphasizing the importance of sleep quality is essential for enhancing overall well-being and health. This study investigates the link between poor sleep quality and key factors affecting wellness, such as mental health and eating disorders. Through a cross-sectional analysis involving 407 participants, utilizing established measures including the Depression Anxiety Stress Scale (DASS-21), the Eating Disorder Examination Questionnaire Short (EDE-QS), and the single-item Sleep Quality Scale (SQS), data was collected and analyzed using SPSS v28 and R-Statistics. The findings reveal a significant correlation (p&lt;0.05) between DASS-21, EDE-QS, and SQS, indicating that individuals experiencing poor sleep quality exhibit higher levels of depression, anxiety, and stress. Furthermore, multinomial logistic regression analysis highlights low sleep quality as a risk factor for both mental health (OR: 1.071, 95% CI: 1.042, 1.102, p&lt;0.05, low vs. high sleep quality), and eating disorders (OR: 1.047, 95% CI: 1.004, 1.092, p&lt;0.05, low vs. high sleep quality). Overall, these results underscore the critical role of sleep quality in mental health and suggest insomnia as a predictive factor for both poor mental well-being and disordered eating habits. Further research through randomized controlled trials is warranted to validate the findings of this cross-sectional study.

Background: This study attempted to construct musculoskeletal JEM using KWCS data and use it to evaluate the burden of these disorders in Korean workers. Methods: This study was conducted using data from the second to the sixth KWCS, and a total of 210,500 people were included. The jobs of the subjects were reclassified based on the unit groups of the 7th Korean Standard Classification of Occupation (KSCO). The intensity of exposure to work-related risk factors for musculoskeletal disorders was classified into ‘high’, ‘moderate’, and ‘low’ for the body segments involving the ‘upper extremities and neck’, ‘lower back’, and ‘lower extremities’. Results: The time of exposure was longest in the standing posture and repetitive hand and arm movements. An analysis of the intensity of exposure by body segments revealed that the highest intensity of exposure was to the upper extremities. For the upper extremities and neck, and the lower back, there was a exposure-response relationship in the association between intensity of exposure and musculoskeletal symptoms. However, for the lower extremities, there was a exposure-response relationship only at high exposure. Conclusion: In this study, a JEM for work-related risk factors for musculoskeletal disorders was constructed for the first time in Korea. The intensity of exposure to musculoskeletal risk factors was estimated for each occupation. The JEM constructed in this study is expected to have high applicability for assessing the risk of musculoskeletal disorders for each job with respect to the upper extremities and neck, and lower back.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n=42) and major NCD (n=164) through DSM-5 criteria on 206 participants aged>65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (=-1.05-p<.0001) and minor NCD (=-0.06-p<.01). In the fully-adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (=0.09-p<.001). The effect of loneliness on IADL (=-0.26-p<.0001) and ADL (=-0.24-p<.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL:=0.26-p<.0001-ADL:=0.05-p=0.01). Minor NCD displayed different levels of MMSE (=6.68-p<.001), but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill’s test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

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.

There are few longitudinal studies on the association between dietary vitamin C and sleep disorders. The aim of this study was to investigate the association between dietary vitamin C intake and various types of sleep disorders, including sleep apnea and insomnia, as well as recommended dietary intakes. A total of 68,221 participants from the UK Biobank were enrolled in the study. Dietary vitamin C intake was calculated by a 24-hour dietary recall questionnaire. We used Cox regression model to assess the association between dietary vitamin C and sleep disorders and restricted cubic spline models to explore potential nonlinear relationships. Stratified analyses and sensitivity analyses were also performed to further test the results. The results showed that vitamin C intake at the Q4 level (132.88-191.51 mg/d) was significantly protective against sleep disorders with an HR (95% CI) of 0.78 (0.65-0.94), and against sleep apnea with an HR (95% CI) of 0.75 (0.62-0.92). The protective effect remained significant in stratified analyses of men and age ≤60 years, and the results were robust in sensitivity analyses. Adequate dietary vitamin C intake may have a protective effect in preventing sleep disorders.

The aim of the current study has been to assess externalizing problems from a gender perspective in the juvenile population. This objective has been evaluated though the Child and Adolescent Assessment System questionnaire (SENA), to measure the dimension of externalized problems. A total of 128 Spanish students took part in the survey, comprising 58 (45.3%) male and 67 (52.3%) female, aged between 12 and 16 years old (M= 13,7; Sd= 1,14). The sample was taken from three High- Schools (state and private-subsidized) in Madrid, Spain. The research for this study was conducted through a descriptive, inferential, quantitative, ex post facto design. The data analysis was performed using SPSS 27.0. The result revealed an increase in externalized problems: Attention (M= 2.65, Sd=.88), Anger Control (M= 2.27, Sd=.85) and Hyperactivity- Impulsivity (M= 2.26, Sd=.68). In addition, female students score highly in Attention Problems (F= 4.124; Sig.: .004), Hyperactivity-Impulsivity (F: 6.18; Sig.: <.001), and Anger Control (F: 2.3; Sig.: .062). This study highlights the impact and increase on students externalized mental health problems currently. It is essential to have a protective environment and promote the development of emotional intelligence, encouraging the mental health in young people. This article is part of the findings of the research project “Therapeutic Innovation Classroom for the accompaniment of teenager with Serious Mental Disorder” (Reference: 2021V/EU-UNED/02).

The generation of forensic DNA profiles consisting of single nucleotide polymorphisms (SNPs) is now being facilitated by wider adoption of next-generation sequencing (NGS) methods in casework laboratories. At the same time, and in part because of this advance, there is an intense focus on the generation of SNP profiles from evidentiary specimens for so-called forensic or investigative genetic genealogy (FGG or IGG) applications. However, FGG methods are constrained by the algorithms for genealogical database searches, which were designed for use with single-source profiles, and the fact that many forensic samples are mixtures. To enable the use of two-person mixtures for FGG, we developed a workflow, MixDeR, for the deconvolution of mixed SNP profiles. MixDeR, a flexible and easy to use R package and Shiny app, processes ForenSeq Kintelligence® (QIAGEN, Inc.) SNP genotyping results and directs deconvolution of the profiles in EuroForMix (EFM). MixDeR then filters the EFM outputs to produce inferred single-source genotypes in reports formatted for use with GEDmatch® PRO. An optional MixDeR output includes metrics that assist with testing and validation of the workflow. As the Shiny app provides a graphical user interface and the software is designed to be run offline, MixDeR should be suitable for use by any laboratory developing FGG capabilities, no matter their bioinformatic resources or expertise.

Improper sitting positions are known as the primary reason for back pain and the emergence of musculoskeletal disorders (MSD) among individuals who spend prolonged time working with computer screens, keyboards, and mice. At the same time, it is well understood that automated technological tools can play an important role in the process of unhealthy habit alteration, so plenty of research efforts are focused on research and technology development (RTD) activities that aim to provide support to the prevention of back pain or the development of MSD. Here, we report on creating a new resource in support of RTD activities aiming at the automated detection of improper sitting positions. It consists of multimodal multisensory recordings of 100 persons made with a video recorder, camera, and wrist-attached sensors that capture physiological signals (PPG, EDA, Skin temperature), as well as motion sensors (three-axis accelerometer). Our multimodal multisensory dataset (MMD-MSD) opens new opportunities for modeling the body stance (sitting posture and movements), physiological state (stress level, attention, emotional arousal, valence), and performance (success rate on the Stroop test) of people working with a computer. Finally, we demonstrate two use cases: improper neck posture detection from pictures and cognitive load detection from physiological signals.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

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.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

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.

Background/Objectives: Direct oral anticoagulants (DOACs) are first-line medications for stroke prevention in non-valvular atrial fibrillation (AF). However, variability in drug response poses risks of hemorrhagic or thromboembolic events. The role of genetics in determining DOAC safety is gaining attention, but evidence linking specific genetic polymorphisms to bleeding risk is lacking. Therefore, the aim of our study was to conduct an Exome-Wide Association Study with 198 non-valvular AF patients treated with rivaroxaban or apixaban, including 97 with bleeding complications and 99 without. Methods: DOAC plasma concentrations, 6-β-hydroxycortisol and cortisol levels in urine were measured for CYP3A4 phenotyping. Sequencing was performed on the DNBSEQ G-400 platform. Single nucleotide variants (SNV) associations with bleeding risk were assessed using logistic regression with additive, dominant, and recessive genetic models. Results: No SNVs reached Bonferroni-corrected significance in any genetic model. Polygenic risk scores (PRS) showed weak predictive ability for bleeding with apixaban. For rivaroxaban, regression indicated that ln Css min/D + 1 index increased with PRS, age, and 6-β-hydroxycortisol/cortisol ratio, but decreased with higher 6-β-hydroxycortisol and coronary heart disease presence. Conclusions: The findings revealed that the residual equilibrium concentration of anticoagulants, including dose-adjusted, cannot alone predict bleeding risk in non-valvular AF patients. No new genetic variants associated with bleeding risk were identified.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different than the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

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.

(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.

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.

Apple-tree (Malus × domestica Borkh.) belongs to the genus Rosaceae. Due to its adaptability and tolerance to different soil and climatic conditions, it is cultivated worldwide for fresh consump-tion. Therefore, the priorities of apple growers are the high-quality of fruits and stable yield for high production. In total about 90 to 95 percent of fruits should fall or be eliminated from apple trees to avoid overcropping and poor-quality fruits. Several technologies such as handwork, me-chanically or chemical substances are used for fruit and bud elimination. The most profitable in commercial orchards is the use of chemicals for elimination, but due to the European Green Deal more environmentally sustainable solutions are required. Elimination of fruitlets is influenced by several factors. Additionally, the apple trees have the self-elimination mechanism. This is de-termined by apple genotype, physiological futures and genetics. This review focuses on the bio-logical factors and genetics mechanisms in apple yield self-regulation for better understanding the regulatory mechanism of fruitlets abscission for future breeding programs targeted on self-regulating yield apple varieties

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.

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.

Monkeypox (mpox) caused by the monkeypox virus (MPXV) is currently the most common orthopoxvirus (OPXV) zoonotic disease. Since 2022, a multi-country outbreak of mpox has been reported with atypically rapid human-to-human transmission. The present work aimed to investigate the frequency of MPXV and OPXV DNA detection in different clinical materials taken at acute and convalescent phases of the infection in Bulgarian patients. A total of 181 clinical samples from 42 Bulgarian patients with possible mpox infections were tested. Screening for MPXV DNA (F3L gene) and OPXV DNA (rpo18 gene) were performed by real-time PCR assays. Of all tested patients six (14%) were confirmed with mpox infection. MPXV DNA was detected in 23/181 (12,71%) and OPXV DNA in 20/181 (11,05%) clinical samples. All confirmed patients were men who have sex with men, aged 23 to 44 (at an average age of 35,17±7,91 years) and two of them were HIV positive. The commonest clinical features of patients were fever (5/6), vesicular-pustular rash: perianal (6/6), penile (4/6), and limbs (4/6). MPXV DNA was found with the greatest frequency in specimens of vesicle contents and nasal/oropharyngeal swabs in 6/6 and 5/6. OPXV DNA mainly was detected in vesicle contents (6/6), nasal/oropharyngeal swabs (4/6), and urine (4/6). In the collected follow-up samples, MPXV DNA was detected in the highest percentage in the specimen's vesicle contents (6/6) and urine (6/6) and not demonstrated in samples of feces and saliva. The laboratory surveillance of MPXV is critical to contain the outbreak and to elucidate the new fast transmission of the virus.

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.

Microgrid (MG) control is essential for efficient, reliable, and sustainable energy management in distributed energy systems. Genetic Algorithm-based energy management systems (GA-EMS) can optimally control a MG by finding global optima and handling complex, non-linear, and non-convex problems, but they can be computationally intensive, making real-time control challenging. Model Predictive Control (MPC)-based EMS predicts future behaviour over a defined horizon, ensuring optimal performance and constraint satisfaction but typically relies on linear models. This paper proposes a novel Genetic Predictive Control (GPC) method, combining GA and MPC to enhance resource allocation, balance multiple objectives, and adapt dynamically to changing conditions. Integrating GA with MPC significantly improves the handling of non-linearities and non-convexity in the system model, leading to more accurate and effective control. Comparative analysis shows that GPC significantly reduces excess power production—surplus power generated beyond load demand—improving resource allocation efficiency. For instance, in the Mutation–Random Selection scenario, GPC reduced excess power to 76.0W compared to 87.0W with GA. Additionally, GPC balances cost, emissions, and power efficiency. In the Crossover-Elitism scenario, GPC achieved a daily cost of $113.94 compared to GA's $127.80, and carbon emissions of 52.83 kg CO2e compared to GA's 69.71 kg CO2e, demonstrating GPC's cost efficiency and environmental benefits. While MPC optimizes a weighted sum of objectives, designing appropriate weights can be challenging and may result in non-convex problems. GA handles multiple, conflicting objectives through multi-objective optimization, providing Pareto-optimal solutions. GPC's dynamic adaptability maintains optimal performance by forecasting future load demands and adjusting control actions. GPC consistently achieves lower emissions than GA across various scenarios and, although it sometimes incurs higher costs, such as $113.94 compared to $131.90 in the Crossover–Random Selection scenario, its holistic approach balances these costs with other metrics, making it cost-effective in the long run. By reducing excess power production and emissions, GPC contributes to economic savings and promotes sustainable practices. These findings underscore GPC's potential as a versatile, efficient, and environmentally beneficial optimization tool for power generation systems.

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.

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.

Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involved clinical assessment through operator-based physical examination, self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating on the feasibility to use machine-learning algorithms fed with data gathered from low-cost and portable instruments to discriminate the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as control group. The diagnosis of TMD has been performed by a skilled operator through the typical clinical scale. Participants underwent to a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree were compared. The k-nearest neighbours based on cosine distance was found as the best performing, achieving performance of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility to use such methodology to support the diagnosis of TMDs in clinical environments.

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.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

(1) Background: In most cases, passive isolation control methods are commonly used for the seismic isolation design of bridge engineering. However, for passive seismic isolation devices, due to their non-adjustable performance parameters, it is challenging to achieve a good seismic isolation effect for structures under random and variable seismic loads in the wide frequency range of 0 Hz to 20 Hz; (2) Methods: the sensitivity of the design parameters of the seismic isolation bearing was analyzed using the optimization center gradient method, and an improved genetic algorithm was employed to quickly optimize and obtain the optimal design parameters; (3) Results: the effectiveness of the three-dimensional seismic isolation bearing was validated through experiments. (4) Conclusions: The multi-factor sensitivity analysis approach used in this study for designing novel isolation bearings is applicable not only to seismic design in bridges but also serves as a reference for parameter design in isolation bearings requiring medium to high precision in seismic performance.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.