Natural killer cells are associated with the pathogenesis of ulcerative colitis (UC), but their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated genes (ANAGs) in UC. Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, 92 differentially expressed genes (DEGs) were screened out by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT, which revealed a higher abundance of activated NK cells in noninflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2) and establish an activated NK-associated gene score (ANAG score). The ANAG score demonstrated excellent diagnostic value and was validated in three external datasets. The expression of the 4 key ANAGs was validated in UC patients and healthy controls (HC) samples. Through scRNA-seq data analysis, higher expression levels of SELP, TIMP1, MMP7, and ABCG2 were observed in post-capillary venules, inflammatory fibroblasts, enterocytes, and immature enterocytes. The cell scores based on the ANAGs showed enrichment in endothelial cells and fibroblasts. In conclusion, we established and validated an ANAG score with the ability to precisely diagnose UC. The 4 key ANAGs have the potential to serve as therapeutic targets in UC.

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify immune-related biomarkers that more effectively predict outcome of glioblastoma. Since heat shock protein 70 (Hsp70) and IL-2 are known to increase the expression of activatory NK cell receptors, recognizing aggressive human tumor cells that present Hsp70 on their cell surface, extracellular Hsp70 levels were determined in glioma patients together with activatory NK cell receptors. All gliomas are membrane Hsp70-positive (mHsp70+) and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly increased extracellular Hsp70 levels are detected predominantly in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. Elevated frequencies of NK cells are associated with a more favorable outcome. Of caution, a glucocorticoid therapy reduces the prevalence of NK cells. In summary, elevated frequencies of Hsp70-reactive NK cells at diagnosis and lower Hsp70 levels predict a more favorable prognosis in glioblastoma patients.

Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.

In the recent years, tubular nanostructures have been related with immense advances in various fields of science and technology. Considerable research efforts have been centered on the theoretical prediction and manufacturing of non-carbon nanotubes (NTs), which meet modern requirements for the developing of novel devices and systems. In this context, diatomic inorganic nanotubes formed by atoms of elements from the 13th group of the periodic table (B, Al, Ga, In, Tl) and nitrogen (N), have received much research attention. In the present work, the elastic properties of single-walled boron nitride, aluminium nitride, gallium nitride, indium nitride and thallium nitride nanotubes were numerically evaluated using the nanoscale continuum modelling approach (also called molecular structural mechanics). The elastic properties (rigidities, surface Young´s and shear moduli, and Poisson´s ratio) of nitride nanotubes are discussed with respect to the bond length of the corresponding diatomic hexagonal lattice. The results obtained contribute to a better understanding of the mechanical response of nitride compound-based nanotubes, covering a broad range from the well-studied boron nitride NTs to the hypothetical thallium nitride NTs.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

A precise understanding of the genes and associated genomes of SARS-CoV2 is important for various reasons such as discovering origin of the virus and virulence and so on. A thorough descriptive understanding of the SARS-CoV2 genomes and other coronavirus of the beta-coronavirus genus is primarily important. In this article, a set of ten genomes of four CoVs and their associated genes are considered for this present study. A spatial representations of nucleotide bases including purine-pyrimidine representations of the different genes of the corresponding genomes are quantified using Hurst exponent, Shannon entropy and density estimation of different nucleotides including GC content, in order to draw a comparison and contrast among the ten genomes of different types of CoVs which include MERS, SARS-CoV, HKU1 (Human Coronavirus) and associated their genes.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

Silica fly ash, Certyd aggregate, and an alkaline solution were used to produce lightweight geo-polymer concretes. The compressive strength, water absorption, bulk density and SEM photos showing the structure of the obtained composite were carried out. Tests conducted on the specifi-cation of lightweight geopolymer concretes have revealed significant chemical interactions between the ash aggregate and the geopolymer mortar, particularly when the coarse aggregate surface has been pre-treated with an alkaline solution. Statistical analysis of the experimental data, which in-vestigated the influence of three key variables on compressive strength, water absorption, and bulk density of Lightweight Geopolymer Concrete (LBG), identified the following factors as having the most substantial impact: the quantity of alkali used, the curing temperature, and the concentration of alkali in the mixture. The optimal test series exhibited a commendable compressive strength of 20.14 megapascals (MPa), accompanied by a water absorption rate of 14.72% and a bulk density of 1486.6 kilograms per cubic meter (kg/m³). These findings underscore the importance of alkali con-tent, curing temperature, and alkali concentration in tailoring the properties of lightweight geo-polymer concrete to meet specific performance requirements.

Closely related to the model plant Arabidopsis thaliana, the genus Boechera is known to contain both sexual and apomictic species or accessions. Boechera retrofracta is a diploid sexually reproducing species and is thought to be an ancestral parent species of the apomictic species Boechera divaricarpa. Here we report the de novo assembly of the B. retrofracta genome using short Illumina and Roche reads from 1 paired-end and 3 mate pair libraries. The distribution of 23-mers from the paired end library has indicated a low level of heterozygosity and the presence of detectable duplications and triplications. The genome size was estimated to be equal 227 Mb. N50 of the assembled scaffolds was 2.3 Mb. 27048 protein-coding genes were predicted using a hybrid approach that combines homology-based and de novo methods. Also repeats, tRNA and rRNA genes were annotated. Finally, genes of B. retrofracta and 6 other Brassicaceae species were used for phylogenetic tree reconstruction. Also, a detailed analysis of evolution of the APOLLO apomixis-associated locus was performed. An assembled genome of B. retrofracta will help in the challenging assembly of the highly heterozygous genomes of hybrid apomictic species such as B. divaricarpa.

Natural killer (NK) cells are part of the innate immune system, protects against pathogens and tumor cells and are the main cell effectors of monoclonal antibodies (mAbs) generating antibody-dependent cell cytotoxicity (ADCC). Hence it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. The presence of viral-sculpted NK cell populations has already been described, but the presence of cancer-sculpted NK remains unknown. Cancer induces a broad NK cell dysfunction. We investigated the NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and at least 30 days after treatment, which correlates with tumor cell clearance. The NK lineage largely responded to the tumor by generating antitumor NK cells and renewing the population with a subset of immature NK cells. However, we failed to identify specific “memory-like” subsets. Moreover, in patients in relapse we found essentially the same NK populations that at diagnostic, suggesting that NK cells equally respond to the first or second tumor rise. Finally, previous CMV infection largely affects tumor-associated changes in NK population, but the CMV-associated CD57+NKG2C+ NKs do not appear to play any role in tumor immunity.

Electrochemical methods are used for the treatment of both municipal and industrial wastewater, either independently or in conjunction with biological methods. This conjunction is used for pretreatment or posttreatment of biologically treated wastewater. In our work, we focused on the combination of these processes, where pre-electrolysis was used to produce dissolved iron before the activation process. Electrolysis was also directly introduced into the activation using either iron or carbon electrodes. The surface of one iron electrode was 32.2 cm2, the applied voltage was 21 V, and the supplied current was 270 mA. The surface of one carbon electrode was 7.54 cm2, the supplied current was 82.5 mA, and the applied voltage was 21 V. From laboratory research on the treatment of synthetic municipal wastewater using a combination of electrolysis and activation processes, it resulted that the use of iron electrodes increased the efficiency of phosphorus removal compared to its precipitation with iron salts. The electrolysis had a positive effect on the sedimentation properties of sludge and the destruction of filamentous microorganisms. Electrolysis negatively affected the respiration rates of activated sludge and the efficiency of denitrification. However, it did not have a negative impact on the nitrification activity of the sludge.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

The exploration and identification of targets and pathways for Atopic dermatitis (AD) treatment and diagnosis are critical for AD control. The conventional target exploration approach such as the literature review is not satisfying in terms of efficiency and accuracy. Recently, the bioinformatic approach is drawing attention for its unique advantage of high-volume data analysis for target and pathway exploration; Open Targets Platform is the targets source for this study to extract top 200 high-rank proteins from 3122 AD associated proteins. STRING, Cytoscape, CytoHubba, ClueGo, and CluePedia function had been applied for data analysis. The KEGG Mapper search & colour pathway was the pathway map resource for identified pathways; 23 key hub genes (VDR, KIT, BCL2L11, NFKBIA, KRAS, IL13, JAK2, STAT3, IL21, IL4R, REL, PDGFRB, FOXP3, RARA, RELB, EGFR, IL21R, MYC, CREBBP, NR3C1, IL2, JAK1, and KITLG). Additionally, 8 correlated pathways and the biological process had been identified; Through this study, a viable approach for target and pathway exploration had been presented. The identified AD targets and pathways will be tested for upcoming research for traditional Chinese medicinal herb interactions

The type of tail of sheep is an important economic trait. However, the candidate genes associated with the tail type are uncertain. The objective of this study was to identify the genetic region and genotype responsible for the tail type phenotype. Here we perform a genome-wide association study (GWAS) in 40 large tailed Han sheep and 40 Altay sheep as case and 40 Tibetan sheep as control. The results indicated that a total 31 genome-wide significant SNPs associated with type of tail traits were detected. For significant SNPS loci, determine its physical location, and screening of candidate genes within section. By combining information of previously reported and annotated biological functional genes, we identified SPAG17, Tbx15, VRTN, NPC2, BMP2 and PDGFD as the most promising candidate genes for type of tail traits. Based on the above identified candidate genes on type of tail traits, we selected BMP2 and PDGFD to conduct the genetic effect analysis in a large Altay sheep and Tibetan sheep population. Rs119 T>C in the exon1 of BMP2 gene and 1 SNPs in the exon4 (rs69 C>A) of PDGFD gene were detected, rs119 that located on exon1 of BMP2 gene was TT genotype in Altay sheep, while with CC genotype in Tibetan sheep. On rs69 of PDGFD gene, Altay sheep with CC genotype, however, Tibetan sheep with AA genotype. These results indicated that the significant associations of SNPs detected in GWAS were indirectly caused by the genetic effects of BMP2 and PDGFD on sheep tail fat deposition.

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are comorbidities that result from the sharing of common genes. The molecular background of comorbidities can provide clues for the development of treatment and management strategies. Here, the common genes involved in the development of the two diseases and in memory and cognitive function are reviewed. Network clustering based on protein-protein interaction networks identified tightly connected gene clusters that have an impact on memory and cognition among the comorbidity genes of AD and T2DM. Genes with functional implications were intensively reviewed, and relevant evidence was summarized. Gene information will be useful in the discovery of biomarkers and the identification of therapeutic targets for AD.

NK population is characterized by distinct NK cell subsets which respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e. resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

This research elucidates the dynamic expression of expansin genes during the wheat grain (Triticum aestivum L.) development process using comprehensive meta-analysis and experimental validation. We leveraged RNA-seq data from multiple public databases, applying stringent criteria for selection, and identified 60,852 differentially expressed genes across developmental stages. From this pool, 28,558 DEGs were found to exhibit significant temporal regulation in at least two different datasets, and were enriched for processes integral to grain development such as carbohydrate metabolism and cell wall organization. Notably, 30% of the 241 known expansin genes showed differential expression during grain growth. Hierarchical clustering and expression level analysis revealed temporal regulation and distinct contributions of expansin subfamilies during the early stages of grain development. Further analysis using co-expression networks underscored the significance of expansin genes, revealing their substantial co-expression with genes involved in cell wall modification. Finally, qPCR validation and grain morphological analysis under field conditions indicated a significant negative correlation between expression of select expansin genes and grain size and weight. This study illuminates the potential role of expansin genes in wheat grain development and provides new avenues for targeted genetic improvements in wheat.

The onset of leaf senescence is triggered by external cues and internal factors such as phytohormones and signaling pathways involving transcription factors (TFs). Abscisic acid (ABA) strongly induces senescence and endogenous ABA levels are finely tuned by many senescence-associated TFs. Here, we report on the regulatory function of the senescence-induced TF OsWRKY5 TF in rice (Oryza sativa). OsWRKY5 expression was rapidly upregulated in senescing leaves, especially in yellowing sectors initiated by aging or dark treatment. A T-DNA insertion activation-tagged OsWRKY5-overexpressing mutant (termed oswrky5-D) promoted leaf senescence under natural and dark-induced senescence (DIS) conditions. By contrast, a T-DNA insertion oswrky5-knockdown mutant (termed oswrky5) retained leaf greenness during DIS. Reverse-transcription quantitative PCR (RT-qPCR) showed that OsWRKY5 upregulates the expression of genes controlling chlorophyll degradation and leaf senescence. Furthermore, RT-qPCR and yeast one-hybrid analysis demonstrated that OsWRKY5 indirectly upregulates the expression of senescence-associated NAC genes including OsNAP and OsNAC2. Precocious leaf yellowing in the oswrky5-D mutant might be caused by elevated endogenous ABA concentrations resulting from upregulated expression of ABA biosynthesis genes OsNCED3, OsNCED4, and OsNCED5, indicating that OsWRKY is a positive regulator of ABA biosynthesis during leaf senescence. Furthermore, OsWRKY5 expression was significantly suppressed by ABA treatment, indicating negative feedback regulation of OsWRKY5 expression by ABA. OsWRKY5 is a positive regulator of leaf senescence that upregulates senescence-induced NAC genes leading to expression of ABA biosynthesis and chlorophyll degradation genes.

Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer of chimeric antigen receptor (CAR) expressing T cells has gained FDA approval in hematologic malignancy. However, limited efficacy has been observed utilizing CAR-T therapy in solid tumors. Natural killer (NK) cells are crucial for tumor surveillance and exhibit potent killing capacity of aberrant cells in an antigen-independent manner. Adoptive transfer of unmodified allogeneic or autologous NK cells has shown limited clinical benefit due to factors including low cell number, low cytotoxicity and failure to migrate to tumor sites. To address these problems, immortalized and autologous NK cells have been genetically engineered to express high affinity receptors (CD16), CARs directed against surface proteins (PD-L1, CD19, Her2, etc.) and endogenous cytokines (IL-2 and IL-15) that are crucial for NK cell survival and cytotoxicity, with positive outcomes reported by several groups both preclinically and clinically. With a multitude of NK cell-based therapies currently in clinic trials, it is likely they will play a crucial role in next-generation cell therapy-based treatment. In this review we will highlight the recent advances and limitations of allogeneic, autologous and genetically enhanced NK cells used in adoptive cell therapy.

Preconception or prenatal carrier screening for hereditary deafness is an effective early intervention strategy to reduce the incidence of newborn deafness, but current research is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population and to follow up on pregnancy outcomes in high-risk couples. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. Of the six high-risk couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent successful termination of the birth of two affected fetuses. The frequencies of preconception or prenatal carrier screening for the deafness genes GJB2 and SLC26A4 in 9,993 subjects from China in this study were 2.86% and 2.63%, respectively. In addition, four out of six high-risk couples made alternative reproductive decisions, followed by the successful prevention of the birth of two affected fetuses. These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

A subset of patients with schizophrenia experience physio-somatic symptoms reminiscent of chronic fatigue and fibromyalgia. In schizophrenia, these symptoms contribute to impaired quality of life, and are strongly related to neuro-cognitive deficits, and increased IgA responses to tryptophan catabolites. Negative and PHEM (psychosis, hostility, excitation, mannerism) symptoms, psychomotor retardation (PMR) and formal thought disorders, appear to be manifestations of a single trait reflecting overall severity of schizophrenia (OSOS). In this study, 120 patients with deficit schizophrenia (DEFSCZ) and 54 healthy subjects were assessed with the FibroFatigue (FF) rating scale, and the above-mentioned symptom domains as well as neuro-cognitive tests and biomarkers were measured. In DEFSCZ, there were robust associations between the FF score and all above-mentioned symptom domains, and impairments in semantic and episodic memory and executive functions. Furthermore, the FF score loaded highly on an OSOS latent vector (LV), which showed adequate convergent validity, internal consistency reliability and predictive relevance and fitted a reflective model. Soft Independent Modelling of Class Analogy (SIMCA) showed that the FF items discriminated DEFSCZ from controls with an overall accuracy of 100%. Interleukin IL-1β, IL-1 receptor antagonist (sIL-1RA), tumour necrosis factor (TNF)-α and CCL-11 (eotaxin) explained 66.8% of the variance in the FF score and 59.4% of the variance in OSOS. In conclusion, these data show that physio-somatic symptoms are a core component of the phenomenology of DEFSCZ and are largely mediated by neurotoxic effects of activated immune pathways, including aberrations in CCL-11, IL-1β and TNF-α signalling.

Stalk rot caused by Fusarium fungi is one of the most widespread and devastating diseases of maize, and the introduction of resistant genotypes is one of the most effective strategies for controlling the disease. Breeding genotypes with genetically determined resistance will also allow less use of crop protection products. The aim of the research was to identify molecular markers and associated candidate genes determining maize plant resistance to Fusarium stalk rot. The plant material for the study consisted of 122 maize hybrids, which were sown in plots of 10 m2, in a complete randomized block design, in three repetitions, at two locations (Smolice: 51 42’ 58.904’’ N, 17 13’ 29.13’’ E and Kobierzyce: 50 58’ 19.411’’ N, 16 55’ 47.323’’ E). The analyzed genotypes were simultaneously subjected to next-generation sequencing using the Illumina platform. The results of the observation of the degree of infection and sequencing were used for association mapping, which ultimately resulted in the selection of 10 molecular markers important at both places. Among the identified markers, two SNP markers that are located inside candidate genes play an important role. Marker 4772836 is located inside the serine/threonine-protein kinase bsk3 gene, while marker 4765764 is located inside the histidine kinase 1 gene. Both genes can be associated with plant resistance to Fusarium stalk rot, and these genes can also be used in breeding programs to select resistant varieties.

Brassica napus is an important vegetable and oil crop worldwide. The research is meaningful for yield and plant architecture in B. napus. In this study, one natural mutant (MT) line with determinate and capitulum-like inflorescence was chosen for further study. The paraffin sectioning detected that the inflorescence apex began to split and developed into one terminal flower, starting from five-leaf stage. Genetic analysis indicated that the segregation patterns of inflorescences in the F2 populations supported a digenic inheritance model, which was further approved by BSA-Seq technique. The BSA-Seq method detected two QTL region on C02 (14.27-18.41 Mb) and C06 (32.98-33.68 Mb) for the genetic control of determinate inflorescences in MT plants. In addition, the expression profile in MT compared with WT was analysized, and a total of 133 candidate genes for regulating the flower development (75 genes, 56.4%), shoot meristem development (29 genes, 21.8%) and inflorescence meristem development (13 genes, 9.8%) were identified. Then one joint analysis combing BSA-Seq and RNA-Seq identified two candidate gene of BncTFL1 and BncAP1 for regulating the MT phenotype. Besides, the potential utilization of the MT plants was also discussed.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic ‘Tiny Padhye’. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that nine unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, and one UFGT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of Asiatic ‘Tiny Padhye’ at stages 2 and 3, while they showed an extremely low level of expression in ovaries of Asiatic ‘Yellow Pixels’ during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic ‘Tiny Padhye’. These results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries.

Phylostratigraphic analysis is a way to look anew on phylogenetic data in the evolutionary aspect. It allows counting the evolutionary age based on the analysis of genes, their orthologs and finding the last common ancestor. We performed phylostratigraphic analysis of Arabidopsis thaliana genes associated with several types of abiotic stresses (heat, cold, water-related, light, osmotic, salt, and oxidative) determined by the Gene Ontology annotation. Comparison of the distributions of ages of genes associated with stresses of different type has shown the heat stress to involve older genes while the light stress – younger genes. At the same time, all types of stress are characterized by a significantly higher proportion of old genes (common to all eukaryotes) compared to the whole set of A.thaliana genes. This can be explained by the involvement of basic molecular processes in plant cells into the stress response. Reconstruction and graphical analysis of the gene network of the heat stress educed several clusters associated with different response functions. Some of these clusters contain only ancient genes. The results obtained show that the phylostratigraphic analysis reveals the fundamental features of the organization of gene networks and their evolution.

Tumor immunotherapy represented by immune target blocking and chimeric antigen receptor cell therapy has developed rapidly. Among them, Natural Killer Cell (NK) is gradually becoming another preferred immunotherapy method after T cell immunotherapy because of its unique killing effect in innate immunity and adaptive immunity. Although NK cell therapy has achieved promising results in clinical trials, there are still some problems, such as low efficacy in solid tumors, insufficient penetration of NK cells and high cost of treatment. Nanomaterials are expected to be an excellent tool to improve the anti-tumor immune response of NK cells due to their advantages such as chemical specificity, biocompatibility and simple synthesis. Nanomaterials can enhance the cytotoxicity of NK cells, participate in the modification and noninvasive cell-tracking patterns of NK cells，and mediate their homing and infiltration, and thus significantly improve the efficiency of NK cell immunotherapy. In this review, we will briefly introduce the methods and mechanisms of tumor immunotherapy, emphasize the research progress of NK cell-based immunotherapy and imaging, and finally summarize the direction and research progress of nanomaterials in NK cell-based immunotherapy.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

Salt stress is a major limiting factor for alfalfa yield due to its relatively low salt tolerance. High soil salinity adversely impacts alfalfa growth and development, leading to reduced yield. Melatonin (MT) is known to play a significant role in enhancing plant resistance to abiotic stresses. However, the mechanisms underlying melatonin-mediated abiotic stress responses, particularly salt stress, are not well understood. To address this gap, we conducted a study focusing on germinating alfalfa seeds under salt stress. Physiological indexes and transcriptomics analyses were carried out on the germinated seeds to investigate the effects of melatonin on alfalfa seedlings under salt stress conditions. Our results revealed that the application of melatonin led to an increase in shoot length and fresh weight of alfalfa seedlings under salt stress. Moreover, key physiological indexes such as peroxidase (POD) activity and glutathione (GSH) content were enhanced, while levels of malondialdehyde and superoxide anions decreased. Transcriptomic analysis identified a total of 2,131 differentially expressed genes in the salt-treated group, with 726 up-regulated and 1,405 down-regulated genes, while the MT-treated group showed 2896 differentially expressed genes, of which 1,097 were up-regulated and 1,799 were down-regulated. Further, KEGG enrichment analysis highlighted the enrichment of differentially expressed genes in pathways including flavonoid biosynthesis, ABC transporter, glutathione metabolism, and the MAPK signaling pathway, with these pathways more significantly enriched in the MT-treated group. These findings collectively suggest that melatonin plays a crucial role in alfalfa's response to salt stress and offer new insights into the genomic mechanisms underlying melatonin-mediated salt tolerance in alfalfa.

: In this study we evaluated, if single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1 and CYP27B1 are associated with Mandibular Retrognathism (MR). Samples from biologically-unrelated patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients having a retrognathic mandible (SNB<78º) were selected as cases and those with an orthognathic mandible (SNB=78º–82º) were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256 and rs307247), VDR (rs7975232), CYP24A1 (rs464653) and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p<0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 MR and 43 controls were included. In the genotype and allele distribution analysis, the SNPs rs694, rs307247 and rs464653 in were associated with MR (p<0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1 and CYP27B1 genes are associated with the presence of mandibular retrognathism.

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected in Norwestern Spain (2017- 2019). These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA, tetB, blaROB1, blaTEM, ermA, ermC, mphE and msrE. Relevant resistance percentages were shown to teracyclines, sulphamethoxazole/trimethoprim and tiamulin, thus suggesting that P. multocida isolates were mostly susceptible to amoxicillin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin and macrolides. 29.2% of isolates were resistant to more than two antimicrobials. The tetracycline resistance genes (tetA and tetB) were detected in 22.9% of the isolates, but none was positive to both simultaneously; blaROB1 and blaTEM genes were found in one third of isolates but both genes were detected simultaneously in only one isolate. ermC gene was observed in 41.7% of isolates, a percentage that decreased until 22.9% for msrE; finally, ermA was harboured by 16.7% and mphE was not found in any of them. Six clusters were established based on hierarchical clustering analysis on antimicrobial susceptibility for the twelve antimicrobials. Generally, it was unable to foresee the antimicrobial susceptibility pattern for each family and the association of each particular isolate inside the clusters established from the presence or absence of the resistance genes analyzed.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Salt stress is one of the major abiotic stresses that lead to crop yield reduction worldwide. Melatonin (MT), an endogenous hormone synthesized in plants, plays an important role in responding to abiotic stimuli such as drought, salinity, heat, cold, etc. However, the molecular mechanisms of MT-mediated abiotic stresses remain to be better understood. In order to explore the key genes and pathways of melatonin in alleviating salt stress, physiological and biochemical indicators as well as transcriptomics profile were conducted in alfalfa seedlings. The results showed that the germination rate, bud length and fresh weight of alfalfa seedlings added with melatonin were higher than those treated with salt alone. In addition, Malondialdehyde (MDA) and Superoxide anion (O2-) contents also displayed a decreasing trend. The activity and content of Superoxide dismutase (SOD)、peroxidase (POD) and Glutathione (GSH) increased to varying degrees. In order to further reveal the molecular mechanism of MT-mediated salt tolerance of alfalfa, transcriptome analysis was performed on alfalfa seedlings. 2,181 differentially expressed genes (DEGs) were obtained in the salt-treated group, including 780 upregulated genes and 1,401 down-regulated genes, while 4,422 DEGs were obtained in the MT group, among which 1,438 were upregulated and 2,984 were downregulated. By using GO functional annotation and KEGG pathway enrichment, we found that DEGs were mainly enriched in the biosynthesis of flavonoids, isoflavones, plant hormones, Glutathione (GSH), soluble sugars and other substances, as well as in the ABC transporter and MAPK signaling pathways. Among them, the DEGs in the MT group was more enriched in these pathways, suggesting that MT can combat salt stress by regulating the expression of genes related to phytohormone and antioxidant capacity, which has important reference value for the breeding of salt-tolerant alfalfa and other crops.

Safe water is a global public health concern amid increasing scarcity and pollution. Bottled water production and consumption contribute to these problems. This study examines tap water consumption in Italy, assessing associated sociodemographic factors and related health outcomes such as obesity and self-perceived health status. Data from the Italian National Statistics Institute's "Aspects of daily life" survey (N=45,597) were analyzed. Covariates included education, age, gender, economic status, region, concerns about waste and climate change, consumption of carbonated drinks excluding water, alcohol consumption, consumption of vegetables, consumption of snacks, body mass index, and self-perceived health status. Bivariate analyses and mixed-effect logistic regression models explored the associations. People who drink tap water were 19,674 with a higher prevalence in people aged 45 to 59 old, people with a graduate/post-graduate degree diploma, with optimal economic resources, and concerned about waste production and climate change, coming from the North-East regions of Italy. Underweight people showed a higher prevalence of TW assumption as well as those who drink less than occasionally carbonated drinks, drink alcohol, consume vegetables more than once a day, and snacks less than once a week with a satisfying level perceived health status. Regressions showed that all age classes are less likely to drink tap water than people younger than 20 years old. The category with “inadequate” economic resources is more likely to consume tap water. Low educational classes show a low likelihood of consuming tap water as well as Islands. A concern about waste production and climate change is associated with an increased likelihood of assuming tap water. Tap water consumption was negatively associate with obesity but not with a satisfactory Self-perceived health status. Insights from this study can inform public health strategies.

Background: Identifying genetic mutations that lead to spermatogenic impairment is essential for offering patients informed genetic counseling and preventing the transmission of genetic defects to their offspring, often through the use of advanced reproductive technologies. Objectives: The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Methods and Materials: Genetic variants that may cause infertility are identified by combining targeted next generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Results: Our analysis revealed five distinct affected genes covering seven SNPs: based on targeted NGS panel and WES data, namely SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150) and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. Discussion and Conclusions: These findings strongly support the hypothesis that dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2 and DRC7 mutations are associated with male infertility, specifically azoospermia, further examination of this genetic function is required.

Selenium is essential for the synthesis and function of various selenoenzymes, such as glutathione peroxidases, selenoprotein P, and thioredoxin reductase, which play an important role in both antioxidant defense and limiting oxidative damage. Associations between serum selenium concentration and obstetric complications as well as pregnancy outcomes has been reported in many studies. The aim of this study was to determine whether the dietary intake of selenium, its concentration in serum and the activity of glutathione peroxidase in subsequent trimesters of pregnancy affect the birth condition of newborns assessed on the basis of the Apgar score in the 1st and 5th minute of life, birth weight, body length and head and chest circumference in physiological and complicated pregnancy course. Twenty-seven pregnant women at a mean age 29.6 ± 4.8 years from the Lower Silesia region of Poland were recruited to the study, 55% of studied group had pregnancy complications. The mean reported Se intake and serum selenium content for Polish pregnant women was in the first trimester – 56.53 μg/day and 43.75 μg/l, the second trimester – 61.79 μg/day and 41.77 μg/l and the third trimester – 58.37 μg/day and 42.13 μg/l, respectively. In the subgroup of pregnant women with a physiological pregnancy course, a weak, although statistically significant, positive correlation was found in the first trimester between Se intake and the length (R=0.48, p=0.019) and birth weight of newborns (R=0.472, p=0.022), and in the second trimester with the APGAR score at 1 (R=0.680, p=0.005) and 5 minutes (R=0.55, p=0.033), as well as in the third trimester with th APGAR score at 1 minut (R=0.658, p=0.019). The GPX value had a strong positive correlation with the APGAR score at 1 min. (R=0.650, p=0.008) in the second trimester and with the birth weight of the newborns (R=0.598, p=0.039) in the third trimester. There was no correlation between newborns' birth measurements and serum selenium concentration. In the subgroup of pregnant women with pregnancy complications, a strong, statistically significant, negative correlation was found between Se intake in the second trimester and gestational age (R=-0.618, p=0.032), and in the third trimester, a positive correlation between Se concentration in serum and head circumference (R=0.587, p=0.021). The obtained results indicate that there is a relationship between the maternal selenium status during pregnancy, both in terms of the intake of this element, its serum concentration as well as the glutathione peroxidase activity, and the anthropometric parameters of the newborn, such as birth weight, length and APGAR score, especially in the group with physiological course of pregnancy, but when pregnancy complications occur, these relationships lose their importance.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Parts of shotgun cartridges are a significant source of plastic litter in the marine environment. Empty cartridge shells may not be picked up by the hunter who fired them, and plastic wads that serve to separate the propellant from the shot load, are lost down-range when a shot is fired. Such litter items constitute a cosmetic and aesthetic problem on coastlines and may cause harm to marine animals and in the later stages of decomposition break down into harmful micro plastic particles. There exists no reliable estimate of the global exposure of marine ecosystems to this plastic source. However, in some countries it has been subject to closer examination, including for example, Denmark where the annual contribution of plastic wads into marine systems was estimated to 600,000 pieces (c2 tonnes), and the accumulated density of washed-up items (both wads and shells) was 3.7 items per 100 m coastline. Increasing awareness of this problem has caused scientists, hunters’ communities and governments to suggest altered practice including transition to the use of biodegradable cartridge components, first and foremost wads as this item is invariable lost during hunting. Several manufacturers provide shotgun cartridges containing biodegradable wads based on different types of materials, including fibers and various types of plastics, for example PVAL (poly(vinyl alcohol)) and PHA (polyhydroxyalkanoate). In this paper, we review the most recent literature on the amounts and related environmental hazards of plastic dispersed from hunting ammunition into marine ecosystems. We summarize the market availability of shotgun cartridges with biodegradable wads and discuss chemical, technical, economical and legal aspects of a transition to the use of such products.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

CYP1B1 loss-of-function (LoF) is the main known genetic alteration present in recessive primary congenital glaucoma (PCG), an infrequent disease characterized by delayed embryonic development of the ocular iridocorneal angle and caused by poorly understood molecular mechanisms. To model CYP1B1 LoF underlying PCG, we developed a cyp1b1 knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries the c.535_667del frameshift mutation that results in a 72% mRNA reduction with residual mRNA predicted to produce an inactive truncated protein (p.(His179Glyfs*6)). Craniofacial defects and jaw maldevelopment were observed in 23% of somatic mosaic F0 crispant larvae (144 hpf). These early phenotypes were not detected in KO F3 larvae (144 hpf) but 27% of adult fishes (4 months) showed uni or bilateral craniofacial alterations, indicating the existence of incomplete penetrance and variable expressivity. These phenotypes increased to 86% in the adult offspring of inbred progenitors with craniofacial defects. No glaucoma-related phenotypes were observed in the cyp1b1 mutants. Transcriptomic analyses of the offspring (7dpf) of KO cyp1b1 progenitors with adult-onset craniofacial defects revealed that differentially expressed genes were functionally enriched in groups related with extracellular matrix and cell adhesion, cell growth and proliferation, lipid metabolism (retinoids, steroids, and fatty acids, and oxidation-reduction processes which included several cytochrome P450 genes) and inflammation. In summary, this study shows the complexity of phenotypes and molecular pathways associated with cyp1b1 LoF, with species-dependency, and provides evidence for dysregulation of extracellular matrix gene expression as one of the mechanisms underlaying pathogenicity associated with cyp1b1 disruption.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

To characterize the fecal microbiota of lactating Bactrian camels, this study employed a random selection of camels, assigning them to three groups: the first parity group, the third parity group, and the fifth parity group. The fecal microbial community of lactating camels was assessed using 16S rRNA amplicon sequencing, and the resulting library was sequenced on an Illumina NovaSeq platform. The first parity group was characterized by Verrucomicrobiaceae as a distinctive bi-omarker, whereas Clostridiaceae exhibited a similar role to the third parity group. In terms of functional analysis, the relative abundance of the Steroid biosynthesis pathway was highest in the first parity group, whereas the fifth parity group demonstrated a higher relative abundance of the Tuberculosis pathway compared to the other groups. The first parity group exhibited the greatest presence of seven types of enzymes, whereas the fifth parity group displayed the highest levels of two specific enzymes. Additionally, a positive association was observed between the relative abundance of the Steroid biosynthesis pathway and Verrucomicrobiaceae. Furthermore, the relative abundance of the Tuberculosis pathway displayed positive correlations with 14 enzymes. In conclusion, this study revealed that different parity was associated with distinct fecal microbial ecologies in lactating Bactrian camels.

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

Presently, Jordan confronts a double substantial challenge of enhancing energy security and mitigating greenhouse gas emissions. One of the most encouraging avenues to attain the objectives of sustainable development, energy security, and environmental conservation is to enhance the integration of renewable energy into the generation of electricity. In pursuit of this goal, the Jordanian government intends to expand investments in the green energy sector, with solar and wind energy poised to play a key role in satisfying energy demands and cultivating an environmental sustainability. This paper aims to examine the distinctive dynamics, challenges, obstacles, and potential solutions corresponding to the establishment of community solar and wind farms in Jordan suburban areas. It aims to highlight the opportunities and barriers influencing the track of sustainable energy adoption in the country. Through a comprehensive analysis of the Jordanian context, the goal is to extract insights that can guide policies and practices. Additionally, the findings may serve as a valuable benchmark for other regions confronting similar challenges on their pursuit for a sustainable energy future.

Sweetpotato is an important miscellaneous grain crop in China, which is threatened by a variety of diseases and insect pests in the process of cultivation and production. sweetpotato stem rot is one of the common sweetpotato diseases, which seriously affects the yield and quality of sweetpotato. However, there are few studies on the mechanism of resistance to stem rot in sweetpotato. In this study, transcriptome sequencing analysis was carried out on the samples at different stages (T1, T2, T3) of stem rot pathogen infecting Xushu 48, and 44839 (T1-VS-T2), 81436 (T1-VS-T2) and 61932 (T2-VS-T3) differentially expressed genes (DEGs) were obtained. The DEGs were mainly concentrated in Alanine, aspartate and glutamate metabolism (ko00250), Carbon fixation in photosynthetic organisms (ko00710) and Amino sugar and nucleotide sugar metabolism (ko00520) and some candidate genes related to plant pathogen infection, such as receptor-like protein kinase (RLK5, RLK7), LRR receptor-like serine/threonine-protein kinase (SERK1), bHLH137, ERF9, MYB73 and NAC053, were screened. The results of this study provide genetic resources for the research on stem rot resistance of sweetpotato and provide theoretical basis for sweetpotato resistance breeding.

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

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

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

Genome-wide association studies (GWAS) have identified and reproduced thousands of diseases associated loci but many of them are not directly interpretable due to the strong linkage disequilibrium among variants. Transcriptome-wide association studies (TWAS) incorporated expression quantitative trait loci (eQTL) cohorts as reference panel to detect associations with the phenotype at the gene level and were gaining popularity in recent years. For nicotine addiction, several important susceptible genetic variants were identified by GWAS, but TWAS that detected genes associated with nicotine addiction and unveiled the underlying molecular mechanism were still lacking. In this study, we used eQTL data from the Genotype-Tissue Expression (GTEx) consortium as reference panel to conduct tissue specific TWAS on cigarettes per day (CPD) over 13 brain tissues in two large cohorts: UK Biobank (UKBB; N=142,202) and the GWAS &amp; Sequencing Consortium of Alcohol and Nicotine use (GSCAN; N=143,210), and then meta-analyzed the results across tissues while considering the heterogeneity across tissues. We identified three major clusters of genes with different meta-patterns across tissues consistent in both cohorts, including homogenous genes associated with CPD in all brain tissues, partially homogeneous genes associated with CPD in cortex, cerebellum and hippocampus tissues, and lastly the tissue-specific genes associated with CPD in only few specific brain tissues. Downstream enrichment analyses on each gene cluster identified unique biological pathways associated with CPD and provided important biological insights into the regulatory mechanism of nicotine dependence in the brain.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox (Hox) genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Hox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Hox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Background: Condoms have proven to be an effective contraceptive barrier method of family planning and have played a vital role in preventing sexually transmitted diseases including HIV. However, existing evidence shows that utilization of condoms still remains low, especially among youth and adolescents. We aimed to determine the prevalence of condom use and associated factors among the students of Gulu university in Uganda. Methods: A cross-sectional study was conducted among undergraduate students of Gulu University between June and December 2023. The students were accessed from their respective faculties and chosen using a simple random sampling method. Data were collected using a pretested self-administered structured questionnaire. Condom use was defined as use of either male or female condom in the last sexual encounter in the previous six months. Results: A total of 404 participants, with a median age of 23 years (interquartile range (21.5-24) years) were enrolled in the study, 54.2%(n=219) of whom were male. Overall, 81.4%(n=329) of the participants were in senior classes (year 2,3,4, and 5) and 18.6%(n=75) were in their first year of study. The prevalence of condom use was 53.7%(n=217). Prevalence of condom use was 50.2%(n=109) among male and 49.8%(n=108) among female students. Year of study (senior class)(aPR = 1.4, 95% CI = 1.59, 3.54), having a sexual partner (aPR = 2.4, 95% CI = 1.89, 2.94), having a sexual partner within campus (aPR = 2.0, 95% CI = 1.69, 2.45), experience of condom bursting (aPR = 1.3, 95% CI = 1.08, 1.61), having sex in absence of condoms (aPR = 0.6, 95% CI = 0.44, 0.70), alcohol use (aPR = 1.2, 95% CI = 1.01, 1.45) were independently associated with condom use. Conclusion: Just over half of undergraduate students of Gulu university used condoms during sexual encounters. There should be heighten campaigns on condom use to prevent unintended pregnancies and sexually transmitted infections.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

The unique porous crystal structure of zeolite offers various important utilizations, it is one of the considerations in selecting zeolite at this study as component of composite for restraining noise. It so happens, previous experiments show that banana stem has porous structure, fibrous, high flexibility and can be applied as material for many various products including as component of acoustic material. The combination of both is alleged that it has capability in absorbing noise. This paper presents an investigation on the composite that it was synthesized of Activated Zeolite and Banana Stem Fibre in various weight for determining its sound absorption coefficient alpha (a). Activating natural zeolite was conducted by using 6M HCl in order for enlarging zeolite pores. The sound absorption coefficient was measured in the frequency range between 125 Hz up to 6000 Hz. The results show that the different weight of banana stem fibre as component of the synthesized composite affects the value of alpha and shifts the frequency area.

The aim of the present study is to provide new insights into the CO2 and CH4 adsorption using a set of biomass-based activated carbons obtained by physical and chemical activation of olive-stones. The adsorption behavior is analyzed by means of pure gas adsorption isotherms up to 3.2 MPa at two temperatures (303.15 and 323.15 K).The influence of the activation method on the adsorption uptake is studied in terms of both textural properties and surface chemistry. For three activated carbons the CO2 adsorption was more important than that of CH4. The chemically activation resulted in higher BET surface area and micropore volume that lead to higher adsorption for both CO2 and CH4. For methane the presence of mesopores seems to facilitate the access of the gas molecules into the micropores while for carbon dioxide, the presence of oxygen groups enhanced the adsorption capacity.

Apple red flesh coloration is a result of the performance of biochemical pathway involved in the biosynthesis of anthocyanins and anthocyanidins. Based on apple genome analysis, high number of regulatory genes, mainly transcription factors such as MYB, which are components of regulatory complex MYB-bHLH-WD40, and several structural genes (PAL, 4CL, CHS, CHI, F3H, DFR, ANS, UFGT) involved in anthocyanin biosynthesis have been identified so far. In this study, we investigated previously unrecognized genes involved in the constitution of red-flesh apple phenotype. These genes could be concerned as molecular markers for early selection of new apple cultivars. Based on comparative transcriptome analysis of apples with different fruit flesh coloration, we successfully identified and characterized ten genes from plant hormone transduction pathway of: auxin (GH3); cytokinins (B-ARR); gibberellins (DELLA); abscisic acid (SnRK2 and ABF); brassinosteroids (BRI1, BZR1 and TCH4); jasmonic acid (MYC2); and salicylic acid (NPR1). In presented studies an analysis of their expression profiles was performed in immature and ripe fruits of red-fleshed cultivars. Generally, we have uncovered, the set of the novel genes, mediating regulation of the abscisic acid, salicylic acid, cytokinins and jasmonic acid signaling and preliminarily described their role in anthocyanin biosynthesis, accumulation and degradation. Their expression was not characterized in apple fruits so far. Presented study, allowed to underline the relationship of genes from hormone signal transduction pathway with UFGT gene, directly responsible for anthocyanin color transformation as well as confirmed their crucial role of plant hormone regulation and anthocyanin accumulation during apple fruit ripening.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

The present study provides molecular insight into the mechanisms underlying energy dissipation and lubrication of a smooth contact lubricated by an ionic liquid. We have performed normal and lateral force measurements with a surface forces apparatus and by colloidal probe atomic force microscopy on following model systems: 1-ethyl-3-methyl imidazolium bis-(trifluoro-methylsulfonyl)imide, in dry state and in equilibrium with ambient (humid) air; the surface was either bare mica or functionalized with a polymer brush. The velocity-dependence of the friction force reveals two different regimes of lubrication, boundary-film lubrication, with distinct characteristics for each model system, and fluid-film lubrication above a transition velocity V*. The underlying mechanisms of energy dissipation are evaluated with molecular models for stress-activated slip and flow, respectively. The stress-activated slip assumes that two boundary layers (composed of ions/water strongly adsorbed to the surface) slide pass each; the bond dynamics and the strength of the interaction at the slip plane dictate the change in friction -decreasing, increasing or remaining constant- with velocity in the boundary-film lubrication regime. Above a transition velocity V*, friction monotonically increases with velocity in the three model systems. Here, layers of ions slide past each (“flow”) under a shear stress and friction depends on a shear-activation volume that is significantly affected by confinement. The proposed friction model provides a molecular perspective of the lubrication of smooth contacts by ionic liquids and allows identifying the physical parameters that control friction.

A pattern of NK cell heterogeneity in each individual determines proliferative and functional responses of NK cells to activating stimuli. Obtaining the progeny of a single cell by cloning original population is one of the ways to study the NK cell heterogeneity. In this work, we used single cell sorting into a plate and stimulation by IL-2 and gene-modified K562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21) that led to generation of phenotypically confirmed and functionally active NK cell clones. We applied two models of clone cultivation, which differently affected their phenotype, lifespan and functional activity. The first model, which included weekly restimulation of clones with K562-mbIL21 and IL-2, resulted in the generation of relatively short-lived (5-7 weeks) clones of highly activated NK cells. HLA-DR expression in the expanded NK cells correlated strongly with IFN-γ production. The second model, in which NK cells were restimulated mainly with IL-2 alone, produced long-lived clones (8-14 weeks) that expanded up to 10⁷ cells with lower ability to produce IFN-γ. Our method is applicable for studying variability in phenotype, proliferative and functional activity of the certain NK cell progeny in response to the stimulation, which may help in selecting NK cells best suited for clinical use.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

Alkali-activated materials, sometimes called geopolymers, can be used as alternative cementitious materials to conventional Portland cement. There is a significant current interest in these materials due to their low CO2 footprint. Typical applications of alkali-activated materials are within civil engineering, however, potential applications as well cementing material within oil & gas are also being studied with emerging interest. This paper presents a systematic study of compressive strength development from 1 to 28 days for metakaolin-based alkali-activated cement. The results show that compressive strength is highly dependent upon the initial Si/Al ratio in the mix design, as well as the concentration of the activator solution. Furthermore, due to the relatively low initial reactivity of the used metakaolin material, different types of co-binders were included in the slurry composition to improve early strength development. The two different co-binders tested were another, more reactive metakaolin material and Blast Furnace Slag (GGBFS). It was found that both these co-binders performed as intended, by ensuring early strength development via precipitation of K-A-S-H and C-A-S-H gels, respectively, and also by enabling subsequent strength development due to improved dissolution of the low-reactive metakaolin.

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Solanesol is a noncyclic terpene alcohol composed of nine isoprene units and it mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). Here, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase, two 1-deoxy-d-xylulose 5-phosphate reductoisomerase, two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase, four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase, two 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, six isopentenyl diphosphate isomerase, and two solanesyl diphosphate synthase (SPS) genes were identified to be involved in solanesol biosynthesis. Furthermore, the two N. tabacum SPS (NtSPS1 and NtSPS2), which had two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs, and leaves from four growing stages, corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthetic genes and the accumulation of solanesol in tobacco.

Quantum cryptography revolutionizes secure information transfer, providing defense against both quantum and classical computational attacks. The primary challenge in extending the reach of quantum communication comes from the exponential decay of signals over long distances. Addressing this challenge, we have developed Quantum-protected Control-based Key Distribution (QCKD), overcoming transmission range limitations by monitoring signal leakages and rendering leaked quantum states significantly non-orthogonal. This paper reports on the experiments with the QCKD, conducted over a 1,707 km fiber line. We demonstrate advancements in critical components of the protocol, showing its remarkable scalability and adaptability for extended distances and multi-user configurations.

Activated carbon (AC) is an effective adsorbent for creatinine removal in hemoperfusion. However, the hemocompatibility and adsorption capacity of AC was required to be improved furthermore. Heparin, a widely used anticoagulant biomacromolecule, could improve the hemocompatibility of the absorbents in different ways based on its molecular weight. Thus, it was necessary to study the surface modification with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) on improvement of hemocompatibility and adsorption. In this study, UFH and LMWH were respectively grafted on AC through polyethyleneimine as an intermediate layer. The modification of AC about morphology, mechanical strength and pore structure was characterized by XPS, SEM, TA and BET. It was found that compared with AC, the morphology and mechanical strength AC-UFH and AC-LMWH could be well maintained, but the BET surface was decreased due to the grafting of macromolecules. Furthermore, AC-UFH and AC-LMWH showed the better hemocompatibility on protein adsorption, APTT and platelet activation compared with AC, in which AC-LMWH had lower fibrinogen adsorption and longer APTT than AC-UFH. Besides, it was found that AC, AC-UFH and AC-LMWH had no significant effect on blood cell composition. Finally, the adsorption capacity of adsorbents for creatinine was evaluated. Although there was no significant difference between AC-UFH and AC-LMWH, it was found that heparin could be interacted with creatinine to enhance the adsorption capacity when compared with AC-PEI. This study deepened the understanding of anticoagulation of heparinized surface and provided a theoretical basis for adsorbents in hemoperfusion.

Alopecia refers to the continuous shedding of hair from the scalp or other areas. Genetic factors are the most common of the variety of causes of alopecia. Male pattern baldness, also known as androgenic alopecia, is prevalent. Recently, the interest in hair loss treatment has increased due to the growing number of people experiencing anxiety and stress related to hair loss. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE has a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has the potential to be an effective treatment for androgenic alopecia.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Alkali-activated materials are alternative building binders, where secondary raw materials are processed. Possibility to use landfilled waste materials in their preparation, increases their potential application in construction practice, and therefore they are subject to extensive research, especially in recent years. This paper briefly summarizes interesting results of an experiment aimed at verifying the possibility of applying cement by-pass dust (CBPD) in the preparation of alkali-activated materials. The research work was focused on the possibilities of using these wastes for the preparation of small elements of garden architecture. The paper briefly evaluates in particular the results of X-ray diffraction, which were subjected to three types of binder pastes differing in the amount of used activator. In the experiment, a mixture of blast furnace granulated slag, fly ash and cement by-pass dust was alkali activated with sodium metasilicate.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

Staphylococcus aureus (S. aureus) is recognized worldwide as one of the major agents of dairy cow intra-mammary infections. This microorganism can express a wide spectrum of pathogenic factors used to attach, colonize, invade and infect the host. The present study evaluated 120 isolates from eight different countries that were genotyped by RS-PCR and investigated for 26 different virulence factors to increase the knowledge on the circulating genetic lineages among the cow population with mastitis. New genotypes were observed for South African strains while for all the other countries new variants of existing genotypes were detected. For each country, a specific genotypic pattern was found. Among the virulence factors, fmtB, cna, clfA and leucocidins genes were the most frequent. The sea and sei genes were present in seven out of eight countries; seh showed high frequency in South American countries (Brazil, Colombia, Argentina), while sel was harboured especially in one Mediterranean country (Tunisia). The etb, seb and see genes were not detected in any of the isolates, while only two isolates were MRSA (Germany and Italy) confirming the low diffusion of methicillin resistance microorganism among bovine mastitis isolates. This work demonstrated the wide variety of S. aureus genotypes found in dairy cattle worldwide. This condition suggests that considering the region of interest might help to formulate strategies for reducing the infection spreading.

Spent coffee grounds (SCG) have great potential as a useful, value-added biological material. In this context, activated carbon (AC) was prepared from SCG by an activation process using H3PO4 at 600°C in air and used as an adsorbent for the azo dye AO7, a model molecule for dye colorants found in textile industry effluents. X-ray diffraction, SEM and BET revealed that the AC was predominantly amorphous, consisting of a powder of 20-100 µm particles with mesopores averaging 5.5 nm in pore size. Adsorption kinetics followed a pseudo-second-order law, while the Langmuir model best fitted experimental isotherm data (maximum capacity of 119.5 mg AO7 per AC g). Thermodynamic parameters revealed that adsorption was endothermic and spontaneous. All the characterizations indicated that adsorption occurred by physisorption via mainly - interactions. The best experimental removal efficiency optimized by means of a Box-Behnken design and response surface methodology was 98% for an initial AO7 concentration of 20 mg.L-1 at pH 7.5 with a dose of 0.285 g.L-1 of AC and a contact time of 40 min. These results clearly show that activated carbon prepared from SCG can be a useful material for efficiently removing organic matter from aqueous solutions.

This study aimed to elucidate the antibacterial efficacy and unique chemical compositions generated from plasma-activated water (PAW) when utilized a novel vaginal cleansing device. We conducted an analysis of antibacterial activity against probiotics and several chemical compositions including ions under various operational parameters of PAW, including electrical power (12 and 24 V), treatment duration (1, 10, and 20 min), and stay duration (immediate, 30 and 60 min). Our findings revealed that as treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl−concentrations decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW exhibited no antibacterial effects against a type of probiotic, Lactobacillus reuteri that produces lactic acid for vaginal health. This result demonstrated the ability of the vaginal cleaning device to generate ions, primarily HOCl and some cations (Ca2+ and Mg2+), thereby providing vaginal mucosa protecting and cleansing effects with the vaginal environment.

This work presents the production and incorporation of calcium hydrolyzed nano-solutions at three concentrations (1, 2, and 3 wt.%) in alkali-activated gold mine tailings (MTs) from Arequipa, Perú. A first activator solution of sodium hydroxide (NaOH) at 10M was used. The calcium hy-drolyzed nano-solutions acted as a secondary activator and as additional calcium resource for the alkali-activated materials (AAMs) based on the low-calcium gold MTs. High-resolution trans-mission electron microscopy/energy-dispersive x-ray spectroscopy (HR-TEM/EDS) analyses were carried out to characterize the morphology, size, and structures of the calcium hydrolyzed na-noparticles. Fourier transform infrared (FTIR) analyses then were used to understand the chemical bonding interactions in the calcium hydrolyzed nanoparticles and in the AAMs. Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) and Quantitative X-ray diffraction (QXRD) were performed to study the structural, chemical, and phase compositions of the AAMs; uniaxial compressive tests evaluated the compressive strength of the reacted AAMs; and Nitrogen adsorption-desorption analyses measured the porosity changes at nanostructure level in the AAMs. The results indicate that each increase in the concentration of the calcium hydrolyzed nano-solution had a direct/proportional effect on the mechanical properties of the AAMs samples. The AAMs with 3 wt.% calcium-hydrolyzed nano-solution had the highest compressive strength value of 15.16 MPa, which represented an increase of 62% compared to the original system without nanoparticles and aged under the same conditions of 70°C for seven days. These results provide useful information about the positive effect of calcium-hydrolyzed nanoparticles on gold MTs and their conversion into sustainable building materials through alkali activation.

The remarkable adsorption capacity of graphene derived materials has prompted their examination in composite materials suitable for deployment in treatment of contaminated waters. In this study, crosslinked calcium alginate – graphene oxide beads were prepared and activated by exposure to pH 4 by using 0.1M HCl. The activated beads were investigated as novel adsorbents for the removal of organic pollutants (Methylene Blue dye and the pharmaceuticals Famotidine and Diclofenac) with a range of physicochemical properties. Effects of initial pollutant concentration, temperature, pH and adsorbent dose were investigated and kinetic models were examined for fit to the data. Maximum adsorption capacities q_max obtained were 1334, 35.50 and 36.35 mg g^-1 for the uptake of Methylene blue, Famotidine and Diclofenac respectively. The equilibrium adsorption had an alignment with Langmuir isotherms while the kinetics were most accurately modelled using a pseudo- first –order and second order models according to the regression analysis. Thermodynamic parameters such as ΔG^◦, ΔH^◦ and ΔS^◦ were calculated and the adsorption process was determined to be exothermic and spontaneous.

A valorization process of spent coffee grounds (SCG) was studied. Thus, a two-stage process, a stage of extraction of the polyphenols and a stage of obtaining activated carbon (AC) by a carbonization process, was performed. The extraction was carried out with a hydro-alcoholic solution in a pressure reactor, modifying time and temperature. To optimize the extraction of polyphenols, a two-level factorial design with three replications at the central values was used. The best results were obtained by performing the extraction at 80 °C during 30 min, using a mixture of EtOH:H2O 1:1 (v/v) as extraction solution. Caffeine and chlorogenic acid were the most abundant compounds in the analyzed extracts, ranging from 0.09 to 4.8 mg∙g^-1 and 0.06 to 9.7 mg∙g^-1, respectively. The precursor obtained in the extraction stage were transformed into AC. An experimental design was realized in order to analyze the influence of different variables in the AC obtained process (reaction time and amount of potassium hydroxide used). Actived carbons with BET specific surface (SBET) comprised between 1600 m^2∙g^-1 and 2330 m²∙g^-1 had a microporous surface. Under the optimum conditions, the obtained AC presented a maximum adsorption capacity of methylene blue (qm) between 411 mg∙g^-1 and 813 mg∙g^-1.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Dissolved organic matter (DOM) in the ocean represents about 662 billion tonnes of C, 200 times more than the living biomass. It is produced mainly by microbial primary production. The largest fraction of this DOM is old (>weeks to months) and both chemically and biologically recalcitrant. The remainder is young (seconds to weeks), more labile and surface active. It also changes the rheological properties in the bulk phase of the water and at interfaces including the sea surface microlayer (SML). In order of abundance, this DOM consists of sugars, amino acids, fatty acids and nucleic acids, often incorporated into complex polymers. The DOM molecules are produced by microbial genes, and are further modified by enzymes themselves produced by genes. The properties of ocean water and its interfaces as well as biogeochemical fluxes may thus be modified by ocean microbial genes. These fluxes influence ocean and atmospheric climate, which in return acts on the biota. Therefore the ocean microbial genomes and the fluxes and climates they influence may be subject to Darwinian-type selection. Research programmes need to integrate ocean ecology, rheology, biogeochemistry and genomics, to find the associations among them. Discovery of commercial bioactive molecules may be a bonus.

Plastics have become an important environmental concern due to their durability and resistance to degradation. Out of all plastic materials, polyesters such as polyethylene terephthalate (PET) are amenable to biological degradation due to the action of microbial polyester hydrolases. The hydrolysis products obtained from PET can thereby be used for the synthesis of novel PET as well as becoming a potential carbon source for microorganisms. In addition, microorganisms and biomass can be used for the synthesis of the constituent monomers of PET from renewable sources. The combination of both biodegradation and biosynthesis would enable a completely circular bio-PET economy beyond the conventional recycling processes. Circular strategies like this could contribute to significantly decrease the environmental impact of our dependence on this polymer. Here we review the efforts made towards turning PET into a viable feedstock for microbial transformations. We highlight current bottlenecks in the degradation of the polymer and the metabolism of the monomers and we showcase fully biological or semisynthetic processes leading to the synthesis of PET from sustainable substrates.

A small phylogenetically conserved sequence of 11,231 bp termed FAM247 is repeated in human chromosome 22 by segmental duplications. This sequence forms part of diverse genes that span evolutionary time, the protein genes being the earliest as they are present in zebrafish and/or mice genomes, the long non-coding RNA genes and pseudogenes the most recent as they appear to be present only in the human genome. We propose that the conserved sequence provides a nucleation site for new gene development at evolutionary conserved chromosomal loci where the FAM247 sequences reside. The FAM247 sequence also carries information in its open reading frames that provides protein exon amino acid sequences; one exon plays an integral role in immune system regulation, specifically, the function of ubiquitin specific protease (USP18) in the regulation of interferon. An analysis of this multifaceted sequence and the genesis of genes that contain it are presented.

Reducing CO2 emissions is urgently needed to slow down the impacts of climate change. CO2 capture using an amine solution has been developed and implemented on pilot and commercial scales. However, amine scrubbing, in particular, produces a lot of degraded solvent as waste and is energy intensive. Solid sorbents have been called to overcome those drawbacks. In this work, waste biomass-derived carbon materials were developed and tested for CO2 capture and conversion. Advanced thermal chemical processes i.e. hydrothermal and pyrolysis were applied to produce materials from agri-food waste such as soybean and okara. It was found that the number of functional groups (-C=O and -OH) in activated carbon appears in the synthesized materials, implying the generation of surface oxygenated groups. Preliminary results showed that the synthesized activated carbons are obtained with good yields, and a relatively high surface area, which may be applied as CO2 adsorption materials to solve the CO2 emission problems.

Herein, activated red mud particles are used as an adsorbent for adsorbing phosphorus. Different concentrations of HCl and deionized water are used for desorption tests, and the optimal desorption mechanism is investigated. The Langmuir isothermal model and pseudo-second-order kinetic linear model produce consistent results: the desorption is dominated by the surface desorption of the monomolecular layer, and chemical desorption limits the rate of surface desorption. The desorption thermodynamics indicates that the desorption of phosphorus by the desorbent is spontaneous and high temperature promotes desorption. The particle diffusion model demonstrates that the removal of phosphorus in the form of precipitation from the surface of an activated hematite particle adsorbent occurs primarily via a chemical reaction, and an analysis of the microscopic morphology indicates that the desorption process is primarily accompanied by the dissolution of the metal element Ca, followed by Al and Fe. The desorbent reacts with the active elements in red mud, and the vibration of the [SiO4]2− group calcite or aragonite group of calcium–iron garnet in the functional group disappears. The intensity of the wave peaks of the PO43− groups decreases considerably. Thus, desorption primarily involves the chemical desorption of the monomolecular layer.

Magnetosomes of magnetotactic bacteria consist of magnetic nanocrystals with defined morphologies enclosed in vesicles originated from cytoplasmic membrane invaginations. Although many proteins are involved in creating magnetosomes, a single magnetosome protein, Mms6, can direct the crystallization of magnetite nanoparticles in vitro. The in vivo role of Mms6 in magnetosome formation is debated and the observation that Mms6 binds ferric and not ferrous iron raises the question of how Mms6 could promote the crystallization of magnetite, which contains both ferric and ferrous iron. Here we show that Mms6 is a ferric reductase that reduces ferric to ferrous iron using NADH and FAD as electron donor and cofactor, respectively. Reductase activity is elevated when Mms6 is integrated into either liposomes or bicelles. Analysis of Mms6 mutants suggests that the C-terminal domain binds iron and the N-terminal domain contains the catalytic site. Although Mms6 forms multimers that involve C-terminal and N-terminal domain interactions, a fusion protein with Mms6, which remains a monomer, displays reductase activity, which suggests that the catalytic site is fully in the monomer. These results are consistent with a hypothesis that Mms6, a membrane protein, promotes the formation of magnetite by a mechanism that involves reducing iron.

Actuated carbon (AC) is utilized in various conditions of uses after its disclosure as a solid and dependable adsorbent. A review on AC is introduced along with returning to the wellsprings of AC age; strategies used to produce AC including pyrolysis enactment; actual actuation; synthetic initiation and steam pyrolysis. The significant variables influencing the AC creation, the potential uses of AC and their future possibilities are likewise examined. AC is applied in water, wastewater and leachate medicines in numerous nations, particularly to clean the shading, eliminate the smell and some substantial metals. Taking into account this, an exhaustive rundown of research on compound, physical and organic change strategies of initiated carbon relating to prevent of foreign substance expulsion from watery arrangements was aggregated and investigated. Additionally, the examination of the actual blending strategy and the impregnation technique in enactment with antacid metals shows that the actuated carbon got through actual blending had a higher porosity than the initiated carbon created by the impregnation technique. The uses of initiated carbon items were quickly surveyed.

Transposable elements (TEs) are highly abundant in plant genomes. Environmental stress is one of the critical stimuli that activate TEs. We analyzed a heat-activated retrotransposon named ONSEN in cruciferous vegetables. The multiple copies of ONSEN-like elements (OLEs) were found in all the cruciferous vegetables that were analyzed. The copy number of OLE was abundant in Brassica oleracea, which includes cabbage, cauliflower, broccoli, Brussels sprout, and kale. Phylogenic analysis demonstrated that some OLEs transposed after the allopolyploidization of parental Brassica species. Furthermore, we found that the increasing number of OLEs in B. oleracea appeared to be induced transpositional silencing by epigenetic regulation, including DNA methylation. The results of this study would be relevant to the understanding of evolutionary adaptations to thermal environmental stress in different species.

A large number of microplastics (MPs) have been found in various stages of wastewater treatment plants, which may affect the functional microbial activity in activated sludge and lead to unstable pollutant removal performance. In this study, the effects of different concentrations of polylactic acid microplastics (PLA MPs) on system performance, nitrification and phosphorus (P) removal activities, and extracellular polymeric substances (EPS) were evaluated. The results showed that under the same influent conditions, low concentrations (50 particles/(g TS)) of PLA MPs had no significant effect on effluent quality. The average removal efficiencies of chemical oxygen demand, phosphate and ammonia were all above 80%, and the average removal efficiencies of total nitrogen remained above 70%. High concentrations (200 particles/(g TS)) of PLA MPs inhibited the activities of polyphosphate accumulating organisms (PAOs) and nitrifying bacteria. The specific anaerobic P release rate decreased from 37.7 to 23.1 mg P/(g VSS·h), and the specific aerobic P uptake rate also decreased significantly. The specific ammonia oxidation rate decreased from 0.67 to 0.34 mg N/(g VSS·h), while the change in specific nitrite oxidation rate was not significant. The dosing of PLA MPs decreased the total EPS and humic acid content. As the concentration of PLA MPs increased, microbial community diversity increased. The relative abundance of potential PAOs (i.e., Acinetobacter) increased from 0.08% to 12.57%, while the relative abundance of glycogen accumulating organisms (i.e., Competibacter and Defluviicoccus) showed no significant changes, which would lead to improved P removal performance. The relative abundance of denitrifying bacteria (i.e., Pseudomonas) decreased from 95.43% to 58.98%, potentially contributing to the decline in denitrification performance.