Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei; detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outlining the concerted events in pathogenesis that lead to MNGC formation, discussing the factors that influence MNGC formation and how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.

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.

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. The disease symptoms are characterized by circular lesions with an ash-gray centre and dark brown to purple margins on the leaves. It can lead to significant yield losses if not effectively managed. This study aims to characterize and assess the impact of bacterial biological control agents against C. beticola. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with six of them demonstrating more than 80% control. Identification of the bacteria was carried out through sequencing of the16S rDNA, revealing potentially 12 species belonging to six genera including Bacillus which was represented by four species. Additionally, the bacteria underwent in-depth characterization of biochemical and molecular properties, as well as plant-growth promotion. PCR detection of genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed the bacillomycin, iturin, fengycin, and surfactin encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of lipopeptide structure in the bacteria supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length, weight, and shoot length. The field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained by difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with Strelka2 and GATK4 with Mutect2. Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, CHIT1, CEP170, and CTR9, recurrently altered in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. These observations suggest that IGM may be influenced by non-genetic factors, such as environmental triggers or immune system dysregulation, rather than being primarily a genetic disorder.

Objective We aim to assess the quality of life for women with genitourinary fistulas before and after surgery, utilizing the WHOQOL-BREF questionnaire to contrast the preoperative and postoperative results. Materials and Methods: This quasi-experimental study was conducted at the Department of Urology, SIUT, Karachi, Pakistan, from January to December 2023. We used the WHOQOL-BREF questionnaire to assess the quality of life. Participants completed the questionnaire both before the surgical intervention and three months after successful fistula repair. The collected data were entered and analysed using IBM SPSS v26, with a significance level set at p≤ 0.05. Results The participants had a mean age of 35.50 years, with a standard deviation of 8.87 years. Before undergoing genitourinary fistula repair, the average WHOQOL-BREF score was 12.17 with a standard deviation of 5.77. Following the repair, the mean score showed a significant improvement, rising to 96.67 with a standard deviation of 11.86. This marked improvement was statistically significant, with a p-value of 0.0001. Conclusion This study concludes that genitourinary fistula repair at our tertiary care hospital significantly and positively impacts patients' quality of life. The findings emphasize the critical role of timely and appropriate surgical intervention in improving overall well-being. Continued comprehensive care and support are vital for these patients' holistic recovery and long-term health.

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

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

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Some wrong decisions and faulty practices applied during the repair and restoration of traditional buildings cause more damage to the structures due to the materials used in the repair. In this study, brick, mortar, plaster, and wood samples were taken from one registered building in the Konuralp neighborhood of Düzce Province, which has survived to the present day by preserving its original structural features and reflecting the characteristics of traditional housing. Texture, chemical and petrographic analyses were carried out on the samples. In line with these analyses, a scientific basis was created for selecting material properties in the repair and reuse processes of traditional buildings, and suggestions are made for the analysis of materials specific to traditional buildings in Konuralp.

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

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

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests document sterility and confirm that the collagen structure remained intact without modification. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

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

Objectives: We aim to evaluate technical and clinical outcomes with E-nside stent-graft for thoraco-abdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PAAA) endovascular treatment at our University Hospital Center. Methods: Retrospective analysis of patients electively treated by inner branched EVAR (iBEVAR) between 05/2021 and 03/2023. Demographics, procedural and clinical data were analyzed. Technical success and clinical outcomes, such as access-site related complications were reported. Perioperative and early mortality rate, freedom from aortic reintervention, Target vessels (TVs) patency and endoleak rate were evaluated during the follow-up. Technical aspects (external iliac artery diameter, iliac tortuosity, extent of aortic coverage) were retrospectively analyzed. Results: Twenty-two patients included (age 75.9±5.5; 72.7% male). Aneurism extent was Craw-ford I=4 (18.2%), III=8 (36.4%), IV=5 (22.7%), V=1 (4.5%) and PAAA=4 (18.2%). Mean aortic di-ameter was 63.5±9.9mm. The technical success 95.5% (assisted primary success 100%). The clini-cal success 86.4%. Perioperative and early freedom from all-cause mortality rate 90.9% and 90%, respectively. No case of inter-stage aortic-related mortality reported, as no permanent/temporary spinal cord ischemia (SCI). Seventy-eight out of 81 patent TVs were incorporated through a bridging stent (96.3%). TV success 95.1%. Mean external iliac artery (EIA) diameter 7.5±1.1mm. Twelve patients (six women, 100%) were considered outside the instructions for use (IFU) due to narrow iliac arteries. One access-site related complication reported. Conclusions: Our experience confirms that E-nside has promising technical and clinical success rates, as low reintervention rate, but requires a great sacrifice of healthy aorta and adequate iliac arteries that still represent a limitation, especially among women. Mid- to long-term studies and prospective registries are mandatory to evaluate long-term efficacy and safety, as a comparison between E-nside and other alternative off-the-shelf solution.

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer’s disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells called B1 B cells combined with complement are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

Mitral valve disease is a common heart disease in dogs. The aim of this study was to describe the cases of dogs who underwent mitral valve repair using a v-clamp device and to provide their long-term follow-up data on cardiac function after mitral valve repair. Four dogs with mitral valve regurgitation who experienced coughing and dyspnea underwent surgical mitral valve repair between December 2023 and June 2024. The patients were evaluated by transthoracic and transesophageal echocardiography. Echocardiography revealed mitral valve leaflet regurgitation. Mitral valve repair was performed under general anesthesia using a v-clamp device introduced through an introducer wire guide. Echocardiography was conducted at baseline and the 6-month follow-up. Blood analysis results after surgical repair were normal. Follow-up echocardiography revealed no complications related to the procedure, with all dogs demonstrating improved respiratory signs and quality of life after repair. No adverse reactions were reported after surgery. A v-clamp device was used to repair mitral valve regurgitation in four dogs. Mitral valve repair using a v-clamp device is another treatment option for mitral valve disease in dogs.

Scientists can use the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system, which is a powerful and flexible tool for changing the genome, to change only certain parts of the genome. This has helped researchers figure out how target genes work in biology and disease. CRISPR/Cas9 is made up of a sequence-specific CRISPR RNA (crRNA) set and a generic Cas9 nuclease. The crRNA set tells Cas9 where to cut DNA and cause double-strand breaks. In the next step of cellular DNA repair, insertions, deletions, and swaps are made at specific spots. For CRISPR/Cas9-mediated DNA cleavage to be specific, the target sequences must match the crRNA, and a protospacer nearby motif must be placed after the target sequences. In this article, we talk about how CRISPR/Cas9 works at the molecular level, what it can be used for, what it can't do, and what its future clinical treatment promise might be.

Spontaneous tumours in higher plants can develop depending on plant genotype without any pathogen invasion. Spontaneous tumour formation on the taproots is consistently observed in certain inbred lines of radish (Raphanus sativus var. radicula Pers.). In this work, we have sequenced the genomes of two closely related radish inbred lines that differ in their ability to spontaneously form tumours. We have identified numerous single nucleotide variants (amino acid substitutions, insertions or deletions) that are likely to be associated with the spontaneous tumour formation. Furthermore, we performed the identification of CLE and WOX genes the genomic sequences of the radish inbred lines and, as a result, identified two unique radish CLE genes which probably encode proteins with multiple CLE domains. The results obtained provide a basis for investigating the mechanisms of plant tumour formation and also for future genetic and genomic studies of radish.

Endothelial cells are the crucial inner lining of blood vessels, pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

Background/Objectives Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. Identified risk factors include young age, glenoid bone loss, and off-track Hill-Sachs lesions. This systematic review aims to understand failure rates of arthroscopic revision Bankart repair and if these aforementioned factors influence its success. Methods Following PRISMA guidelines, this systematic review, registered on PROSPERO, included twenty-four articles. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results Key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). Despite generally endorsed effectiveness, recurrence rates have increased over the past four years. Comparative analysis revealed significantly lower recurrence for open Latarjet compared to revision arthroscopic Bankart (p

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly in gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5,397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

The flowering period of rice significantly impacts variety adaptability and yield formation. Properly shortening the reproductive period of rice varieties can expand their ecological range without significant yield reduction. Targeted genome editing, like CRISPR/Cas9, is an ideal tool to fine-tune rice growth stages and boost yield synergistically. In this study, we developed a CRISPR/Cas9-mediated multiplex genome editing vector containing five genes related to three traits: Hd2, Ghd7, and DTH8 (flowering stage genes), along with the recessive rice blast resistance gene Pi21 and the aromatic gene BADH2. This vector was introduced into the high-quality Geng rice variety in Zhejiang province, Jiahe212 (JH212), resulting in 34 T0 plants with various effective mutations. Among the 17 mutant T1 lines, several displayed diverse flowering dates, but most exhibited undesirable agronomic traits. Notably, three homozygous mutant lines (JH-C15, JH-C18, and JH-C31) showed slightly earlier flowering dates without significant differences in yield-related traits compared to JH212. Through special Hyg and Cas marker selection of T2 plants, we identified 7, 6, and 2 fragrant glutinous plants devoid of transgenic components, respectively. These single plants will serve as sib lines of JH212 and potential resources for breeding applications, including maintenance lines for Xian-Geng interspecific three-line hybrid rice. In summary, our research offers practical insights and potential resources for targeted improvement of Geng rice varieties, and would also promote the Geng rice varieties expending from the southward to the northward.

Genetic engineering has become an essential element in developing climate-resilient crops and environmental sustainable solutions to respond to the increasing need for global food security. Genome editing using CRISPR/Cas [Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated protein (Cas)] technology is being applied to a variety of organisms, including plants. This technique has become popular because of its high specificity, effectiveness, and low production cost. Therefore, this technology has the potential to revolutionize agriculture and contribute to global food security. Over the past few years, increasing efforts have been seen in its application in developing higher-yielding, nutrition rich, disease resistant, stress-tolerant “crops” fruits and vegetables. Cas proteins such as Cas9, Cas12, Cas13, and Cas14, among others, have distinct architectures and have been used to create new genetic tools that improve features that are important for agriculture. The versatility of Cas has accelerated genomic analysis and facilitated the use of CRISPR/Cas to manipulate and alter nucleic acid sequences in cells of different organisms. This review provides the evolution of CRISPR technology exploring its mechanisms and contrasting it with traditional breeding and transgenic approaches to improve different stress tolerance. We have also discussed the CRISPR/Cas system and explored three Cas proteins that are currently known to exist: Cas12, Cas13, and Cas14 and their potential to generate foreign DNA free or non-transgenic crops that could be easily regulated for commercialization in most countries.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

Numerous varieties of Capsicum annuum L. with multiple valuable traits, such as adaptation to biotic and abiotic stress factors, can be found in south-east Romania, well known for vegetable cultivation and an important area of biodiversity conservation. To obtain useful information toward a sustainable agriculture, management and conservation of local pepper varieties, we analyzed the genetic diversity and we did deep molecular characterization using Whole Genome Resequencing (WGS) for variant/mutation detection. The pepper varieties used in the present study were registered by VRDS in the ISTIS catalog between 1974 and 2019 and maintained in conservative selection, however, no studies have been published yet using WGS analysis in order to characterize this specific germplasm. The genome sequences, annotation and alignments provided in this study offer essential resources for genomic research as well as for future breeding efforts using the C. annuum local varieties.

The Aspergillus genus comprises fungi that are widely distributed in nature. The Terrei section is particularly important due to its functions in recycling organic matter. Aspergillus hortae is a species from this section that has been isolated from clinical samples, but its role as a pathogenic agent is unclear. In this study, three clinical A. hortae isolates from Colombia, initially identified as A. terreus, were characterised by micro and macro-morphological analysis at 26°C and 37°C. A bioinformatic pipeline was used for molecular typing, which included analysis of whole genome sequences for accurate species identification. Susceptibility assays were also conducted using the microdilution broth method (EUCAST). It was confirmed that this species is intrinsically resistant to Amphotericin B with a minimum inhibitory concentration (MIC) of 2-4 mg/L, and is also thermotolerant. We obtained the in vitro susceptibility profiles for three azole drugs (MIC, 0.25-1 mg/L). The three isolates showed phylogenetic divergence from the reference genome strain. A mutation (M769K) in the MelA ortholog of a hypopigmented isolate, which had the lowest MIC value for AmB (2 mg/L), was identified. This study presents the morphological characterization, molecular typing through whole-genome analysis and identification of susceptibility profiles to azoles and amphotericin B of three clinical isolates of A. hortae from Colombia.

Endometrial cancer (EC) poses a significant global health challenge, with increasing prevalence in 26 of 43 countries and over 13,000 deaths projected in the United States by 2024. This rise correlates with aging populations, the obesity epidemic, and changing reproductive patterns, including delayed childbearing. Despite the early diagnosis in 67% of cases, approximately 30% of cases present with regional or distant spread, leading to nearly 20% mortality rates. Unlike many cancers, EC mortality rates are escalating, outpacing therapeutic advancements until recently. One of the reasons for this was the lack of effective therapeutic options for advanced disease until recently. The introduction of immunotherapy has marked a turning point in EC treatment, particularly benefiting patients with defects in mismatch repair proteins (dMMRs). However, dMMR status alone does not ensure a favorable response, underscoring the need for precise patient selection. This review explores the pivotal role of mismatch repair proteins in EC, emphasizing their heterogeneity, the challenges in their assessment, and their potential as predictive biomarkers.

Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.

The Ylistrum japonicum is a commercially valuable scallop known for its long-distance swimming abilities. Despite its economic importance, genetic and genomic research on this species is limited. This study presents the first complete mitochondrial genome of Y. japonicum. The mitochondrial genome is 19,475 bp long and encompasses 13 protein-coding genes, 3 ribosomal RNA genes, and 23 transfer RNA genes. By selecting 15 Pectinidae species and additional outgroup taxa, we have constructed phylogenetic trees to elucidate the evolutionary placement of Ylistrum within the family Pectinidae. Our analysis reveals that Ylistrum is a basal lineage to the Pectininae clade, distinct from its previously assigned tribe, Amusiini. This study offers critical insights into the genetic makeup and evolutionary history of Y. japonicum, enhancing our knowledge of this economically vital species.

In archaea, the interaction of HerA helicase and NurA nuclease is required for 3' end resection during DNA double-stranded break repair, and its disruption results in unfaithful DNA repair. Interactions transpire by the four conserved domains, including the N-terminal HAS domain (HerA-ATP synthase), which serves as a binding site for the exonuclease NurA. As a HerA hexamer between its two subunits, the conserved C-terminal brace extension functions as an adjacent brace. DBD serves as a location for DNA binding, which causes the DNA strands to be propelled into the HerA pocket to begin unwinding. The putative pore entrance is made up of four helix coils, which provide a suitable charged surface for guiding DNA into the pore. The crystal structure of the complex HerA-NurA allows for the identification of key residues for protein-protein interaction. This allows us to predict that most archaeal HerA orthologs will be able to interact with one another. Archaeal HerA is a homo-hexameric assembly featuring a DNA-binding domain that is conserved. It also features distinctive ATP and NurA binding domains. Following the structure and sequence conservation criteria, we find one HerA ortholog in Pyrobaculum calidifontis and multiple HerA paralogs, but the role of none is established yet.Interestingly, orthologous HerA is part of an Mre11-Rad50 gene neighborhood while paralogous HerA is not, which could be misleading. As a result, it sought to describe the criteria that may be used as a possible fingerprint for identifying orthologous genes, as well as the cloning procedures and tactics that would aid in the confirmation of the HerA helicase in P. calidifontis. Their confirmation is based on PCR cloning and characterization following HerA construct creation.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

Repair mortar is commonly used to rehabilitate reinforced concrete structures or components that exhibit a relatively high level of distresses. Yet, this repair mortar can be contaminated by salt from its service environment. This work employs a two-dimensional finite element model to investigate the transport behavior of ionic species in salt-contaminated and water-saturated repair mortar under an externally applied electric field. The model was experimentally validated and then utilized to evaluate the effectiveness of electrochemical chloride extraction (ECE) with or without electrical injection of corrosion inhibitor (EICI). In the case study, both the ECE alone and the ECE+EICI treatment was found effective in decontaminating the zone in front of the steel rebar. In both techniques, the magnitude of current density has a significant effect on removing chloride out of the mortar and increasing the pH of the pore solution near the rebar, whereas the treatment time any not have a significant effect under some scenarios. The injection of the organic corrosion inhibitor significantly slowed down the removal of chloride. Changes in the ionic distribution in the mortar were generally beneficial in reducing the corrosion risk of the steel rebar and thus extending the service life of the repair mortar.

Capulus danieli, a distinct member of Capulidae, exhibits a unique ecological behaviour by attaching and drilling onto the pecten, distinguishing itself from other gastropods. Herein, we present the first characterisation of the mitochondrial genome of Capulus danieli. The results showed that the genome spans 15600 base pairs, with an A + T content of 71.12% and a G + C content of 28.88%. Within this genetic makeup, we identified 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. Phylogenetic analysis revealed a close evolutionary relationship between Capulus danieli and members of the Ficoidea superfamily. The divergence time estimation suggested that Capulus danieli diverged approximately 52.29 million years ago. These findings significantly contribute to our understanding of the evolutionary history and genetic architecture of Capulus danieli, shedding light on its unique ecological adaptations to the marine environment.

Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Based on converting one important signaling molecule (DAG) to another (PA), DGK plays an important role in plant responses to abiotic stress including waterlogging stress. However, no studies have been reported on the characterization of the DGK gene family in the waterlogging-tolerant kiwifruit germplasm, Actinidia valvata Dunn. Here, we identified 18 AvDGK genes in the A. valvata genome. The phylogenetic analysis showed that AvDGKs can be classified into three clusters, and members within the same cluster have similar domain distribution, exon-intron structures and conserved motif compositions. Chromosome localization analysis revealed that all the AvDGK genes are located across 18 different chromosomes. There were 29 duplicated gene pairs in kiwifruit and all had undergone purifying selection during evolution. Promoter cis-element analysis revealed that the cis-elements within AvDGK genes are associated with multiple functions, including phytohormone signal transduction, stress response, and plant growth and development. The expression pattern analyses indicated that AvDGK play an important role in the fruit development and plant response to waterlogging stress. AvDGKs gene family in the tetraploid A. valvata genome might promote PA synthesis and subsequent signal transduction both under short-term and long-term waterlogging stress. These results provide information regarding the structural characteristics and potential function of DGK genes within kiwifruit and lay a fundamental basis for further research into breeding for enhancing the kiwifruit’s tolerance to waterlogging stress.

DNA double-strand breakage is the most lethal damage to chromosomal DNA. It activates a series of cellular DNA damage response pathways, including DNA damage sensing, control of cell cycle arrest and apoptosis, and DNA repair. DNA damage response pathways are regulated by complex signaling machineries. Of the intracellular signaling cascades, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Because both DG and PA serve as second messengers, DGK activity induces a shift of signaling pathways from DG-mediated to PA-mediated cascades, thereby implicating DGK in the regulation of widely various functions. Reportedly, one member of the DGK family, DGKζ, is intimately involved in the regulation of stress responses through p53 and NF-κB. Stresses such as ischemia and infarction cause DGKζ downregulation. Experimental DGKζ depletion renders cells and mice vulnerable to various stressors such as chemotherapeutic agents and ionizing irradiation. Nevertheless, how DGKζ is involved in DNA repair, a critical event of DNA damage response for survival remains unknown. For this study, we examined how DGKζ depletion affects DNA repair mechanisms. We demonstrated that DGKζ depletion causes attenuation of Akt activation and DNA-PK protein expression upon DNA damage, which might engender downregulated BRCA1 protein synthesis and stability. Results suggest that DGKζ depletion attenuates BRCA1-mediated DNA repair machinery, thereby conferring vulnerability to DNA damage.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

This comprehensive overview of the historical milestones in cell culture underscores key breakthroughs that have shaped the field over time. It begins with Wilhelm Roux's seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel's influential contributions, notably the immortalization of chicken heart cells, mark a significant advancement in cell culture techniques. Holtfreter, Moscona, and Leighton introduced innovations such as 3D cell culture, laying the groundwork for further exploration. The advent of induced pluripotent stem cells by Takahashi and Yamanaka in 2006 was revolutionary, enabling the reprogramming of differentiated cells into a pluripotent state. Since then, recent innovations include spheroids, organoids, and organ-on-a-chip technologies, aiming to mimic the structure and function of tissues and organs in vitro, pushing the boundaries of biological modeling and disease understanding. In this review, we overview the history of cell culture shedding light on the main discoveries, pitfalls and hurdles that were overcome during the transition from 2D to 3D cell culture techniques. Finally, we discussed the future directions for cell culture research that may accelerate the development of more effective and personalized treatments.

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

To fully appreciate genetics, one must understand the link between genotype (DNA sequence) and phenotype (observable characteristics). Advances in high-throughput genomic sequencing technologies and applications, so-called “-omics”, have made genetic sequencing readily available across fields in biology from applications in non-traditional study organisms to precision medicine. Thus, understanding these tools is critical for any biologist, especially those early in their career. This comprehensive review discusses the chronological development of different sequencing methods, the bioinformatics steps to analyzing this data, and social and ethical issues raised by these techniques that must be discussed and evaluated.

It has been more than three decades since the discovery of multifunctional factors, Non-POU Domain-Containing Octamer-Binding Protein, NonO and Splicing Factor, Proline-and Glutamine-Rich, SFPQ. Some of their functions, including their participations in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization have been well-documented. In this review, we focus on the roles of NonO and SFPQ in cell cycle with particular attention to their participation in nonhomologous end joining (NHEJ) and homologous recombination (HR) of DNA damage responses induced by irradiation. In these contexts, absence or malfunction of either or both lead to genome instability and ultimately to apoptosis, cellular senescence, and tumor development. This review also will shed light on NonO and SFPQ function in DNA/RNA/protein binding and their association with Ku heterodimer of the NHEJ pathway required for repair of DNA double-strand breaks (DSBs).

Garcinia indica (Thouars) Choisy (commonly known as Kokum) is an important medicinal plant in Ayurvedic medicine and belonging to the Clusiaceae family. Kokum is a highly traded medicinal plant species of India, dried rind of fruits and butter from seeds are traded in the markets. This study aimed to assemble the complete chloroplast (cp) genome of G. indica and compare it with the previously published cp genome within the Garcinia taxa to identify the potential species-specific barcode marker for Kokum authentication. The assembled cp genome, with a size of 1,56,891 bp, exhibits a typical quadripartite structure. The large single-copy (LSC) region spans 85,580 bp, and the small single-copy (SSC) region spans 17,181 bp, together comprising 64.5% of the genome. The pair of inverted repeats (IRA and IRB) are each 27,065 bp, covering the remaining 35.5% of the genome. A total of 126 unique genes were identified, including 86 protein-coding genes, 32 tRNA genes, and 8 rRNA genes. Phylogenetic analysis using complete cp genomes from 12 species in the Clusiaceae family indicated that 10 Garcinia species form a sister clade. Notably, the ycf1 gene in the LSC region was more divergent within the Garcinia species. This study presents the first report on the chloroplast genome of G. indica. This chloroplast genome resource provides a basis for identifying new DNA barcode marker as well as species-specific marker for herbal drug authentication of Kokum, and species delineation within the Garcinia genus.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Lecanicillium lecanii KMZW-1, is recognized for its potential as a bio-control agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of L. lecanii KMZW-1 and assess its pathogenicity against Bactrocera dorsalis. Whole genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16%. The genome completeness was assessed as 97.93% using BUSCO analysis, AntiSMASH analysis identified 29 gene clusters associated with secondary metabolite biosynthesis providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. The pathogenicity of L. lecanii KMZW-1 was assessed using concentrations ranging from 1×10^4 to 1×10^11 spores/mL. Higher-concentrations (1×10^10 to 1×10^11 spores/mL), resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit regression analysis yielded LogLC50 values as 5.662 for female and 4.486 for male B. dorsalis adults. In summary, L. lecanii KMZW-1 exhibits strong insecticidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of L. lecanii KMZW-1in managing against B. dorsalis populations.

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakens, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized.; (2) Methods: Literature review; (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies; (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

Alterations in myelin, the protective and insulating sheath surrounding axons, affect brain function, as is evident in demyelinating diseases where the loss of myelin leads to cognitive and motor dysfunction. Recent evidence suggests that changes in myelination, including both hyper- and hypo-myelination, may also play a role in numerous neurological and psychiatric diseases. Protecting myelin and promoting remyelination is thus crucial for a wide range of disorders. Oligodendrocytes (OLs) are the cells that generate myelin, and oligodendrogenesis (OLgenesis), the creation of new OLs, continues throughout life and is necessary for myelin plasticity and remyelination. Understanding the regulation of OLgenesis and myelin plasticity within disease contexts is therefore critical for the development of novel therapeutic targets. In our companion manuscript [1], we review literature demonstrating that multiple hormone classes are involved in the regulation of OLgenesis under physiological conditions. The majority of hormones enhance OLgenesis, increasing oligodendrocyte precursor cell differentiation and inducing maturation and myelin production in OLs. Thus, hormonal treatments present a promising route to promote remyelination. Here, we review literature on hormonal regulation of OLgenesis within the context of disorders. We focus on steroid hormones, including glucocorticoids and sex hormones, peptide hormones such as insulin-like growth factor 1, and thyroid hormones. For each hormone, we describe whether they aid in OL survival, differentiation, or remyelination, and we discuss their mechanisms of action, if known. Several of these hormones have yielded promising results in both animal models and in human conditions; however, a better understanding of hormonal effects, interactions, and their mechanisms will ultimately lead to more targeted therapeutics for myelin repair.

Butirosins are naturally occurring aminoglycoside (AG) antibiotics featuring a 4,5-disubstituted 2-deoxystreptamine (2-DOS) with a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. This side chain has been shown to confer resistance against AG modifying enzymes, leading to ongoing studies on the butirosin biosynthetic pathway and the corresponding enzymes. Butirosin is produced by Niallia (formerly Bacillus) circulans and Bacillus vitellinus, with most research focused on the former strain. To date, no whole genome analysis has been performed on B. vitellinus. In this study, we sequenced the complete genome of B. vitellinus NBRC 13296 and performed a comparative analysis of different butirosin biosyntheric gene clusters (BGCs), including those from N. circulans. The complete genome of B. vitellinus NBRC 13296 comprises a 6,331,192 base circlular chromosome with a GC content of 52.68%. The annotation revealed the presence of 5,605 CDSs, 70 tRNA genes, 30 rRNA genes, and 3 ncRNA genes in NBRC 13296. The highest dDDH and ANI values between NBRC 13296 and the most closely related type strain, Paenibacillus chitinolyticus KCCM 41400, were 97.8% and 98.66%, respectively. Based on these genome-based comparative analyses, we propose reclassifying B. vitellinus NBRC 13296 as P. chitinolyticus. Genome mining revealed 18 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of B. vitellinus NBRC 13296, indicating the enormous biosynthetic potential of this strain. The predicted structural diversity of secondary metabolites includes aminoglycoside, PKS, NRPS, PKS-NRPS hybrids, metallophores, phosphonates, terpenes, β-lactones, and RiPP peptides. We then comparatively characterized butorosin BGCs previously studied in several N. circulans strains. Additionally, comparative genome analysis revealed complete butirosin BGCs identified from P. chitinolyticus KCCM 41400, P. chitinolyticus NRRL B-23119, P. chitinolyticus NRRL B-23120, P. chitinolyticus B-14908, P. chitinolyticus YSY-3.1, P. chitinolyticus JMW06, Paenibacillus sp. GbtcB18, Paenibacillus sp. HGH0039, Paenibacillus sp. MZ04-78.2. Finally, we identified the core region consisting of BtrS, BtrN, BtrM, BtrL, BtrA, BtrB, BtrC, BtrD, BtrD, BtrE, BtrF, BtrG, BtrH, BtrI, BtrI, BtrJ, BtrK, BtrO, BtrP, and BtrV, followed by an upstream region organizing BtrQ, BtrW, BtrX, BtrY, and BtrZ in the same transcriptional direction and sequential genetic arrangement, and a downstream region organizing various proteins based on BtrT, BtrR2, BtrU, and BtrR1. Our study provided insights into the reclassification of B. vitellinus NBRC 13296 to P. chitinolyticus and suggested the need for continued studies on butirosin biosynthesis from an enzymatic perspective.

The purpose of this scoping review was to identify gaps in the literature and summarize findings from studies examining the use of silicon-, silica-, and silicate-based toothpastes for the remineralization and repair of mineralized tooth tissues. A 10-year literature search was conducted using PubMed and Scopus, adhering to PRISMA 2020 guidelines. A total of 331 studies were initially identified, with 56 full-text review articles. After selecting the manuscripts, 27 studies were qualitatively analyzed by four reviewers, focusing on the results of both in vivo and in vitro methods. The findings suggest that toothpastes containing silicon, silica, and silicate demonstrate promising results for remineralization and enamel repair, with evidence of mineral layer formation and/or deep enamel surface remineralization under various conditions. Additionally, the use of these toothpastes can lead to the obliteration of dentinal tubules within a few days. The results collectively support the efficacy of these toothpastes in enamel repair. Most of the clinical studies focused on dentine hypersensitivity, followed by white spot lesions. In conclusion, silicon-, silica-, and silicate-based toothpastes (bioactive-Si-toothpastes) can be considered effective based mostly on laboratory studies. There remains a need for more in vivo research studies on enamel and dentin mineral repair. Existing studies provide strong evidence that these technologies can reduce dentin hypersensitivity and promote enamel-dentin repair.

The nutrient absorption and utilization efficiency in the roots of seedlings are beneficial for increasing crop yield. Creating marker assisted selection for wheat root traits can assist wheat breeders in choosing robust roots to maximize nutrient uptake. Exploring and identifying the effect of different nitrogen applications on RSA is of great significance for breeding nitrogen efficient wheat varieties. In this study, A total of 243 wheat varieties native to the Yellow and Huai Valley regions of China were utilized for genome-wide association studies (GWAS). Furthermore, a recombinant inbred line (RIL) population of 123 lines derived from the cross between Avocet and Chilero was utilized for linkage examination and confirmation of the hereditary loci distinguished by GWAS. Five RSA traits include the relative number of root tips (RNRT); relative total root length (RTRL); relative total root surface area (RTRS); relative total root volume (RTRV) and relative average root diameter (RARD) where evaluated under two N conditions—normal N (NN) supply and low N (LN)—to characterize the NUE of each accession. GWAS and linkage analysis were performed by integrating data from the wheat 660k single nucleotide polymorphism (SNP) chip and diversity arrays technology (DArT) to identify genetic loci associated with RSA. The results showed that based on the ratio of RSA related traits under two N supply conditions, a total of 598 SNP markers, which are significantly associated with RSA related traits, were detected at 160 genetic loci by GWAS. A total of 10 QTL loci related to RSA were dis-covered and identified by linkage mapping. In which, three significant RSA related Quantitative Trait Locus (QTL) were identified, namely qRtrl-3D, qRnrt-3D, and qRtrl-7D. The study has the potential to enhance the effectiveness of selecting root traits in wheat breeding programs, offering valuable insights into the genetic underpinnings of nitro-gen use efficiency (NUE) in wheat. This could lead to the creation of NUE wheat varieties by implementing focused breeding strategies.

Salmonella species are important foodborne pathogens worldwide. Salmonella pathogenicity is associated with multiple virulence factors and enhanced antimicrobial resistance. To determine the molecular characteristics and genetic correlations of Salmonella, 24 strains of Salmonella isolated from different sources (raw poultry, human stool, and food) in the Wenzhou area were investigated to determine the distribution of antimicrobial resistance and virulence determinants using whole-genome sequencing (WGS). Aminoglycoside-resistance genes were detected in all samples. Over half of the samples found antimicrobial resistance genes (ARGs) and point mutations for several clinically frequently used antibiotic, β-lactamases, tetracyclines, and fluoroquinolones. Of these strains, 62.5% were predicted to be multidrug-resistant (MDR). The quinolone-modifying enzyme gene aac(6')-Ib-cr, detected in five samples (S1–S4 and S10), were located on integrons. Analysis of Salmonella pathogenicity island (SPI) profiles suggests that serotypes with close genetic relationships share the same distribution of virulence factors, revealing a link between genotype and SPI profiles. CgMLST analysis indicated that five isolates S14–S18 were closely related to strains originating from the UK, suggesting that they may have been introduced from the UK. Data from this study may enrich the molecular traceability database for Salmonella and provide a basis for effective public health policies.

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with physiological responses analyzed. Vasoconstriction was mediated by an increase in TRP channels, TRPA1 (p=0.012) and TRPM8 (p<0.001), within cortical defects enhancing sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and VEGF expression (p < 0.001), promoting angiogenesis vital for bone regeneration. Increased expression of osteogenic proteins PGC-1α (p = 0.039) and RBM3 (p<0.008) suggests stimulated reparative processes. Enhanced osteoblast differentiation and ALP presence at days 5 (three-fold, p=0.014) and 10 (two-fold, p=0.010) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.010) indicating presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy's multifaceted effects on bone repair, offering insights for therapeutic strategies.

Keywords: Tendon injuries; Mallet finger; Suture techniques

The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

Physical activity is widely recognized as a biotherapy by WHO in the fight and prevention of bone diseases such as osteoporosis. It reduces the risk of disabling fractures associated with many comorbidities, and whose repair is a major public health and economic issue. Bone tissue is a dynamic supportive tissue that reshapes itself according to the mechanical stresses to which it is exposed. Physical exercise is recognized as a key factor for bone health. However, the effects of exercise on bone quality depend on exercise protocols, duration, intensity and frequency. Today, the effects of different exercise modalities on capillary bone vascularization, bone blood flow and bone angiogenesis remain poorly understood and unclear. As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis-osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials. Thus, this review aims to clarify the link between physical activities, vascularization and bone repair.

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

Aortic transection, a near-complete tear through the layers of the aorta, is a critical condition often resulting from trauma such as motor vehicle collisions. The urgency of managing aortic transection underscores the critical need for effective interventions. We report the case of a male in his early 50’s with no significant medical history who presented to the emergency department following a motor vehicle collision, sustaining multiple injuries including a descending thoracic aortic transection. Rapid diagnostic assessment confirmed the severity of the injury, necessitating immediate intervention. Endovascular aortic repair (EVAR) was successfully employed, highlighting its efficacy in managing acute aortic injuries. The patient responded well to treatment, underscoring the importance of timely intervention in improving patient outcomes. This case emphasizes the critical role of rapid diagnostic assessment and endovascular intervention in managing life-threatening thoracic aortic injuries, particularly in the acute setting.

Fusarium solani KMZW-1, is recognized for its potential as a biocontrol agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of F. solani KMZW-1 and assess its pathogenicity against Bactrocera dorsalis. Whole genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16% and fungus identified as F. solani KMZW-1. The genome completeness was assessed as 97.93% using BUSCO analysis, DFVF sequence identifier was Fusarium 0G092560.1, AntiSMASH analysis identified 29 gene clusters associated with secondary metabolite biosynthesis providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. Comparative genomic analysis found 269 unique genes of F. solani KMZW-1 and the collinearity analysis exhibited a high degree of synteny with Fusarium solani-melongenae. The pathogenicity of F. solani KMZW-1 was assessed using concentrations ranging from 1×10^4 to 1×10^11 conidia/mL. Higher concentrations (1×10^10 to 1×10^11 conidia/mL), resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit regression analysis yielded LogLC50 values as 5.662 for fe-male and 4.486 for male B. dorsalis adults. In summary, F. solani KMZW-1 exhibits strong insecti-cidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of F. solani KMZW-1 in managing against B. dorsalis populations.

Mesenchymal Stem Cells (MSCs) secretions, usually containing growth factors, cytokines, and chemokines, have improved wound healing via a paracrine mechanism. This makes them particularly valuable as potential cell therapeutics. Similarly, wound healing is mainly regulated via paracrine signaling of growth factors, cytokines, and chemokines. Chronic wound healing has prolonged inflammatory, proliferative, or remodeling phases, resulting in tissue fibrosis and non-healing ulcers. The growth factors, cytokines, and chemokines secreted by MSCs can be applied to wounds by transplanting cells or using the secretome/conditioned medium (CM) of MSCs, which contains these secreted bioactive molecules. For their success in increasing the wound healing rate, MSCs offer a promising option for treating chronic wounds. This review provides a concise summary of current knowledge of the biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role of MSCs in wound healing by increasing wound healing rate with the secretion of growth factors, cytokines, and chemokines. In addition, the function and type of MSCs also have been discussed.

Whole genome alignment (WGA) is a critical process in comparative genomics, facilitating the detection of genetic variants and aiding our understanding of evolution. This paper offers a detailed overview and categorization of WGA techniques, encompassing suffix tree-based, anchors-based, and graph-based methods. It elaborates on the algorithmic properties of these tools, focusing on performance and methodological aspects. The paper underscores the latest progress in WGA, emphasizing the increasing capacity to manage the growing intricacy and volume of genomic data. However, the field still grapples with computational and biological hurdles affecting the precision and speed of WGA. We explored these challenges and potential future solutions. This paper aims to provide a comprehensive resource for researchers, deepening our understanding of WGA tools and their applications, constraints, and prospects.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.

Worldwide, hernia repair represents one of the most frequent surgical procedures encompassing a global market valued at several billion dollars. This type of surgery usually requires the implantation of a mesh that needs the appropriate chemical, physical and biological properties for the type of repair. This review thus presents a description of the types of hernias, current hernia repair methods, and the state of the art of prosthetic meshes for hernia repair providing the most important meshes used in clinical practice by surgeons working in this area classified according to their biological or chemical nature, morphology and whether bioabsorbable or not. We emphasise the importance of surgical site infection in herniatology, how to deal with this microbial problem, and we go further into the future research lines on the production of advanced antimicrobial meshes to improve hernia repair and prevent microbial infections, including multidrug-resistant strains. A great deal of progress has been made in this biomedical field in the last decade. However, we are still far from an ideal antimicrobial mesh that can also provide excellent integration to the abdominal wall, mechanical performance, low visceral adhesion and minimal inflammatory or foreign body reactions, among many other problems.

To address the response of small RNAs (sRNAs) biogenesis to drought stress, we identified sRNAs biogenesis genes, including 11 encoding argonauts (AGO), 8 encoding dicer-like proteins (DCL), and 9 encoding RNA-dependent RNA polymerases (RDR) in the peach genome. Notably, the largest numbers of sRNAs biogenesis genes are located to chromosome 1. The PAZ, PIWI, and MID domains were identified in PpAGOs, while the ribonuclease IIIa and IIIb domains were characterized in PpDCLs. The RDRP domain was recognized in PpRDRs. Orthologous similarity and collinearity analyses between Arabidopsis and peach revealed 5, 1, and 2 collinear blocks in AGOs, DCLs, and RDRs, respectively. Moreover, 41, 40, and 42 cis-acting elements were located in the promoters of PpAGOs, PpDCLs, and PpRDRs, respectively, with the majority related to drought stress response. Analysis of RNA sequencing (RNA-seq) data revealed that sRNAs biogenesis genes were involved in drought stress response in different tissues. Furthermore, the expression of candidate genes was verified in two peach cultivars, Beijing 2-7 (BJ2-7) and Sinai (SN), which are drought tolerance and sensitive, respectively. Interestingly, the expression of PpAGO2b, PpDCL2b, PpDCL4, and PpRDR4 genes was induced in ‘BJ2-7’ but inhibited in ‘SN’ under drought stress. Overall, this study provides insight into the roles of sRNA biogenesis genes in response to drought stress in peach.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

A genome represents the complete collection of genetic material in an organism or cell. This genetic information is encoded in nucleic acids, which can be either single or double-stranded and arranged in linear or circular forms. DNA, the most common type of genetic material, consists of just four nucleotides: adenine, guanine, thymine, and cytosine. These nucleotides are organized in a double helix structure, a discovery made by Watson and Crick. The sequence of these nucleotides forms the basic blueprint of a gene or genome. The process of determining this sequence is known as genome sequencing. The field of genome sequencing has evolved dramatically over time, advancing from sequencing short DNA fragments to analyzing millions of base pairs. Initially, efforts were focused on determining the sequence of individual genes, but now whole genome sequencing is both rapid and widely accessible. Recent improvements in sequencing technology emphasize faster, more accurate results, lower costs, and better data analysis. Sanger sequencing, which became the gold standard for DNA sequencing for about thirty years, was instrumental in completing various genome sequences, including the human genome. It laid the groundwork for newer sequencing methods. Today, these newer methods, known collectively as “Next-Generation Sequencing” (NGS), include several generations of technology. Second-generation methods, such as Illumina, Pyrosequencing, ABI/SOLiD, and Ion Torrent Sequencing, and third-generation methods like PacBio and Helicos Sequencing, have advanced the field further. Fourth-generation technology, such as Nanopore sequencing, is also emerging. Most modern research now relies on NGS for analyzing biological sequences, and understanding these technologies offers insight into current methods and future developments.

With an ever increasing amount of research data available, it becomes constantly more important to possess data literacy skills to benefit from this valuable resource. An integrative course was developed to teach students the fundamentals of data literacy through an engaging genome sequencing project. Each cohort of students performed planning of the experiment, DNA extraction, nanopore sequencing, genome sequence assembly, prediction of genes in the assembled sequence, and assignment of functional annotation terms to predicted genes. Students learned how to communicate science through writing a protocol in the form of a scientific paper, providing comments during a peer-review process, and presenting their findings as part of an international symposium. Many students enjoyed the opportunity to own a project and to work towards a meaningful objective.

An analysis of 1300+ existing ACE mutations revealed that 400+ are damaging and led us to hy-pothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer’s disease (AD) [Danilov, 2024]. Here we quantified blood ACE levels in EDTA-plasma from 41patients with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates. We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C and G325R are truly damaging and, likely, transport-deficient, with ACE levels in plasma only ~50% of controls. Another AD-associated ACE mutation, R1250Q, in the cytoplasmic tail, did not cause a decrease in ACE and, likely, did not affect surface ACE expression. We have also developed a method to identify patients with anti-catalytic mutations in the N domain. These mutations may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD. Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has potential to identify individuals at an increased risk of late-onset AD. These individuals may benefit from future preventive or therapeutic interventions involving a combination of chemical and pharmacological chaperones, as well as proteasome inhibitors, aiming to enhance ACE protein traffic. This approach has been previously demonstrated in a cell model of the transport-deficient ACE mutation, Q1069R [Danilov, 2010].

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Major depressive disorder (MDD) is a prevalent mental health condition with substantial social and economic consequences. This study focuses on the interplay between genetic and environmen-tal factors in MDD, with particular emphasis on epigenetic mechanisms such as stochastic epige-netic mutations (SEMs), epigenetic age acceleration, and epigenetic drift. We conducted a meta-analysis of DNA methylation patterns across six datasets (n=1125 MDD cases, 398 controls in whole blood; n=95 MDD cases, 96 controls in brain tissues) from the Gene Expression Omnibus. The analysis did not reveal significant global methylation differences between MDD cases and controls. However, a brain-specific probe (cg25801113) near the SHF gene consistently exhibited hypomethylation, suggesting its potential relevance to MDD. SEMs were assessed, revealing a dis-tinct burden at the gene level in MDD cases, though no significant findings emerged for epigenetic age acceleration, indicating it may not play a central role in MDD. The study also identified rare epivariations in specific genes unique to MDD cases. In blood tissue, 51 genes were associated with these unique epivariations, while 1 gene was highlighted in the brain tissue. These results un-derscore the importance of exploring rare epivariations in understanding the molecular mecha-nisms underlying MDD and offer potential targets for further investigation.

Snakes are a vital component of wildlife resources and are widely distributed across the globe. Bungarus multicinctus, a highly venomous snake, is found in central and southern China. B. multicinctus is a highly venomous snake and is distributed in central and southern China. Snakes are an ancient group of reptiles, and their genome resources can provide important clues for understanding the evolutionary history of reptiles. Meanwhile, genomic resources play a crucial role in comprehending the evolution of species. So far, the genomic resources of snakes are a rarity. In 2021, a snake sample was collected from Beiliu Longgukeng, Guangxi, which was identified as B. multicinctus through morphological identification. In this study, we present a highly contiguous genome of B. multicinctus with a size of 1.51 Gb. The genome contains a repeat content of 40.15%, with a total length exceeding 620 Mb. Additionally, we annotated a total of 24,869 functional genes. This research is of great significance for comprehending the evolution of B. multicinctus and provides a genomic basis for the genes involved in venom gland function.

Enterovirus A71 (EV-A71) infection is a major cause of hand, foot and mouth disease (HFMD) which may be occasionally associated with severe neurological complications. There are currently a lack of treatment options for EV-A71 infection. The Raf-MEK-ERK signaling pathway, in addition to its critical importance in the regulation of cell growth, differentiation and survival, has been shown to be essential for virus replication. In this study, we investigated the anti-EV-A71 activity of vemurafenib, a clinically approved B-Raf inhibitor used in the treatment of late stage melanoma. Vemurafenib exhibits potent anti-EV-A71 effect in cytopathic effect inhibition and viral load reduction assays, with half maximal effective concentration (EC50) at nanomolar concentration. Mechanistically, vemurafenib interrupts both EV-A71 genome replication and assembly. These findings expand the list of potential antiviral candidates of anti-EV-A71 therapeutics.

The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as transcription, replication, recombination or DNA repair. The DNA sequence is a major factor influencing the position of nucleosomes on genomes. Different sequence motifs can promote or inhibit the nucleosome formation, thus influencing the accessibility to the DNA. Sequence-encoded nucleosome positioning having functional consequences on cell processes can then be selected or counter-selected during evolution. We review the interplay between sequence evolution and nucleosome positioning evolution. We first focus on the different ways to encode nucleosome positions in the DNA sequence, and to which extent these mechanisms are responsible of genome-wide nucleosome positioning in vivo. Then, we discuss the findings about selection of sequences for their nucleosomal properties. Finally, we illustrate how the nucleosome can directly influence sequence evolution through its interactions with DNA damage and repair mechanisms. This review aims to provide an overview of the mutual influence of sequence evolution and nucleosome positioning evolution, possibly leading to complex evolutionary dynamics.

Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Species identification and phylogenetic relationships clarification are fundamental goals in species delimitation. Yet these tasks pose challenges when based on morphologies, geographic distribution, and genomic data. Previously, two new species of fern genus Bolbitis, B. × multipinna and B. longiaurita, were described based on morphological traits, are phylogenetically intertwined with B. sinensis and fail to form monophyletic groups. To address the unclear phylogenetic relationships within the B. sinensis species complex, RAD sequencing was performed on 65 individuals from five populations. Our integrated analysis of phylogenetic tree, neighbor net, and genetic structure, indicate that the B. sinensis species complex should not be considered as separate species. Moreover, our findings reveal differences in the degree of genetic differentiation among five populations, ranged from low to moderate, which might be influenced by geographical distance and gene flow. The Fst values also confirmed that genetic differentiation intensifies with increasing geographic distance. Collectively, this study clarifies the complex phylogenetic relationships within the B. sinensis species complex, elucidates the genetic diversity and differentiation across the studied populations, and offers valuable genetic insights that contribute to the broader study of evolutionary relationships and population genetics within the Bolbitis species.

Background The aims of this study were to assess the peri-operative morbidity, mortality and long-term survival of octogenarians undergoing ATAAD repair, and to compare open and closed distal anastomosis techniques. Methods This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni and multi-variable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival. Results Fifty octogenarians patients were included (median age - 82 years, closed distal – 22, open distal - 28). Median CPB time was 187 minutes (open distal vs closed distal group; 219 minutes vs 115.5 minutes, p30 days or return to theatre; HR; 4.1, p=0.02) predicted adverse survival. Open distal anastomosis did no impact survival. Conclusions – ATAAD repair in selected octogenarians has favourable short and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

This study presents a case report demonstrating an anomalous origin of the right subclavian artery from the aortic arch, accompanied by proximal dilation and a retro-esophageal course, characteristic of arteria lusoria and Kommerell's diverticulum. The research highlights the clinical significance of this anomaly and discusses its management strategies, emphasizing the importance of precise surgical intervention in addressing this condition.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Scale drop disease virus (SDDV), a double-stranded DNA virus in the family Iridoviridae, has been reported widely in southeast Asian countries as a causative agent of scale drop syndrome (SDS) in Asian seabass. SDS have resulted in high mortality and significant economic losses to the aquaculture industry. This study demonstrated the use of metagenomic methods to investigate bacterial and viral communities present in infected fish tissues and recovering a complete genome of the causative agent named SDDV TH7_2019. Characterization of the TH7_2019 genome revealed a genome size of 131 kb with 134 putative ORFs encoding viral proteins potentially associated with host apoptosis manipulation. A comparative genome analysis showed a high degree of amino acid identity across SDDV strains, with variations in number of repeat sequences and mutations within core genes. Phylogenetic analyses indicate a close relationship among SDDV genomes. This research enhances our understanding of the genetic diversity and evolutionary relationship of SDDV, contributing valuable insights for further development of effective control strategies of SDDV.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

The demand for sustainable cosmetics leads to the search for natural and biotechnology ingredients. The present study reports the development of multifunctional lip moisturizer containing levan (LEV) from Bacillus subtilis natto, sophorolipids (SOP) from Starmerella bombicola and Citrus paradisi (OCP) essential oil , using simplex-centroid experimental design. The formulations were evaluated physicochemically, pharmacotechnically and by DPPH assay. The optimized formulation was selected through Response Surface Method and the evaluation of its efficiency in lip hydration was carried out using bioimpedance method and sensory analysis. The formulations showed pH compatible with the lip region and remained stable after centrifuge test and thermal stress in preliminary stability. Spreadability varied between 415.3 and 1217.1 mm2, moisture retention was above 95%, and antioxidant capacity was around 50% for all formulations. The optimized formulation, containing 0.4% LEV and 0.8% SOF, helped to maintain the lip hydration already shown by the participants; 85% of them reported improvement in this aspect. The incorporation of these actives is innovative and helps in the development of future works, through the use of a new non-invasive and low-cost technique, not previously described in other studies, in association with relevant sensory analyzes in the field of cosmetology.

Multilineage-differentiating stress-enduring (Muse) cells, a cell subgroup from mesenchymal stem cells (MSCs), are pluripotent cells with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

Gold nanoparticles (AuNPs) have been used in a broad range of applications conferring to bio-molecules diverse proprieties such as deliver, stabilization and reduction of adverse effects of drugs or plant ex-tracts. Polyphenolic compounds from Bacopa procumbens (BP) are able to modulate proliferation, adhesion, migration and cell differentiation, reducing artificial scratch area in fibroblast cultures and promoting wound healing in in vivo model. Here, chemically synthetized AuNPs conjugated with BP (AuNP-BP) were characterized by Uv-Vis, ATR-FTIR, DLS and zeta-potential. Results showed over-lapping FTIR spectra of polyphenolic compounds from B. procumbens capping the AuNPs, stable size by the DLS and zeta potential, AuNP-BP was 44.58 nm, the zeta-potential of AuNPs was -36.3±12.3 mV after conjugation with the BP; - (AuNP-BP), the zeta-potential was reduced to -18-2±7.02 mV. Enhancement of wound healing effect were evaluated by morphometric, histochemical and FTIR changes in rat wound excision model. Results showed that the nanoconjugation process reduced 100 folds BP concentrations to have the same wound healing effect of BP alone. Besides histological and FTIR spec-troscopy analyses, demonstrated that AuNP-BP treatment displayed better macroscopical performance; the reduction on inflammatory cells, and the increased synthesis and better organization of collagen fibers.

DNA damage repair lies at the core of all cells’ survival strategy, including cancerous. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on Tousled like Kinases have brought significant clarity on the effectors of these kinases which stands to regulate DSB repair. In addition to their well-established role in the DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation as well as defined steps during NHEJ ends processing were earlier hints of its important involvement broadly in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.

This experimental study investigates the effect of scarf geometry in restoring the impact response of scarf patched 3 mm thick glass-fibre reinforced polymer (GFRP) matrix composite laminates. Traditional circular along with rounded rectangular scarf patch configurations considered as repair patches. Experimental measurements revealed that the temporal variations of force and energy response of the pristine specimen are close to that of circular repaired specimens. The predominant failure modes were witnessed only in repair patch which include the matrix cracking, fibre fracture, delamination and no discontinuity in adhesive interface was witnessed. When compared with the pristine samples, the top ply damage size of the of the circular repaired specimens is larger by 9.91 %, while that of the rounded rectangular repaired specimens is larger by 434.23 %. The results show that circular scarf repair is more suitable choice of repair approach under the condition of 37J low-velocity impact event even though the global force-time response is similar.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responds to immunotherapy. The relationships between tumor DNA damage response, the immune system and immunotherapy have recently attracted attention. Accumulating evidence indicate that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsible to immunotherapy, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of gastric adenocarcinoma. The results showed that DRGS high score patients showed significantly better therapeutic outcomes compared to DRGS low score patients (P < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocytes infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival and may benefit more from ICB therapy, as compared to the low-score patients. Therefore, the DRGS and its scoring system may have implications in tailoring immunotherapy in gastric cancers.

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA-rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for the different cell lines. Thus, we extended the Geant4-DNA application with an updated TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA-rejoining kinetics of the HSGc-C5s cells. Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5s cells.

This study compared the Biodentine (BD) and MTA in repair of furcation perforation (FP) in a dog model in terms of inflammatory cell count and new hard tissue formation through histological and immunohistochemical evaluations. Ninety six teeth in six adult mongrel dogs were divided according to the time of repair into two groups (48 teeth/3 dogs each); immediate and delayed repair of the induced FP. Each group was divided into three subgroups (16 teeth each) according to the evaluation periods; 1, 2, and 3 months. Each subgroup was further subdivided into four subdivisions according to the material used; MTA (6 teeth), Biodentine (6 teeth), negative control (2 teeth) and positive control (2 teeth). In experimental and positive control samples, the teeth were instrumented and obturated then, a FP was performed. The perforations were sealed according to the groups and subdivisions. Histopathology and immunohistochemical analysis using Osteonectin antibodies were performed for assessment of the inflammatory cell count and new hard tissue formation. In all groups and subgroups, there were no significant differences between MTA and BD in the inflammatory cell count and new hard tissue formation (P>0.05). Biodentine can alternate the MTA as a FP repair material.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

A signal analysis of the genoma sequenced of coronavirus variants: B.1.1.7, B.1.135, B.1.429-B.1.427, B.1.525 and P1 is presented. We deal with a certain type of finite alternating sum series having independently distributed terms associated with binary (0,1) indicators for the nucleotide bases A,C,G,T. This method provides additional information to conventional Similarity comparisons and Power Spectrum approaches. It leads to uncover distinctive patterns regarding the intrinsic data organization of genomic sequences according to its progression along the nucleotide bases position. Hence, the method could be useful for survelliance of genoma variants.

Despite advances in algorithms and computational platforms, de-novo genome assembly remains a challenging process. Due to the constant innovation in sequencing technologies (Sanger, SOLiD, Illumina, 454, PacBio and Oxford Nanopore), genome assembly has evolved to respond to the changes in input data type. This paper includes a broad and comparative review of the most recent short-read, long-read and hybrid assembly techniques. In this review, we provide (1) an algorithmic description of the important processes in the workflow that introduces fundamental concepts and improvements; (2) a review of existing software that explains possible options for genome assembly; and (3) a comparison of the accuracy and the performance of existing methods executed on the same computer using the same processing capabilities and using the same set of real and synthetic datasets. Such evaluation allows a fair and precise comparison of accuracy in all aspects. As a result, this paper identifies both the strengths and weaknesses of each method. This comparative review is unique in providing a detailed comparison of a broad spectrum of cutting-edge algorithms and methods.

Characterization of genetic diversity, population structure and linkage disequilibrium is prerequisite for proper management of breeding programs and conservation of genetic resources. In this study, 186 chickpea genotypes including advanced “Kabuli” breeding lines and Iranian landrace “Desi” chickpea genotypes were genotyped using DArTseq-Based SNP markers. Out of 3339 SNPs, 1152 markers with known chromosomal position were selected for genome diversity analysis. The number of mapped SNP markers varied from 52 (LG8) to 378 (LG4), with an average of 144 SNPs per linkage group. The chromosome size that covered by SNPs varied from 16236.36 kbp (LG8) to 67923.99 kbp (LG5), while LG4 showed higher number of SNPs, with an average of 6.56 SNPs per Mbp. Polymorphism information content (PIC) value of SNP markers ranged from 0.05 to 0.50, with an average of 0.32, while the markers on LG4, LG6 and LG8 showed higher mean PIC value than average. Un-weighted Neighbor Joining cluster analysis and Bayesian-based model population structure grouped chickpea genotypes into four distinct clusters. Principal component analysis (PCoA) and Discriminant Analysis of Principal Component (DAPC) results were consistent with that of the cluster and population structure analysis. Linkage disequilibrium (LD) was extensive and LD decay in chickpea germplasm was relatively low. A few markers showed r²≥0.8, while 2961 pairs of markers showed complete LD (r²=1) and a huge LD block was observed on LG4. High genetic diversity and low kinship value between pairs of genotypes suggesting the presence of a high genetic diversity among studied chickpea genotypes. This study also demonstrated the efficiency of DArTseq-based SNP genotyping for large scale genome analysis in chickpea. The genotypic markers provided in this study are useful for various association mapping studies when combined with phenotypic data of different traits such as seed yield, abiotic and biotic stresses and therefore can be efficiently used in breeding programs to improve chickpea.