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Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma

BackgroundIn the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244.MethodsTo directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments.ResultsCD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244−/− bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors.ConclusionOur study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Form perception is a cognitive correlate of the relation between subitizing ability and math performance.

"Subitizing" defines a phenomenon whereby approximately four items can be quickly and accurately processed. Studies have shown the close association between subitizing and math performance, however, the mechanism for the association remains unclear. The present study was conducted to investigate whether form perception assessed on a serial figure matching task is a potential non-numerical mechanism between subitizing ability and math performance. Three-hundred and seventy-three Chinese primary school students completed four kinds of dot comparison tasks, serial figure matching task, math performance tasks (including three arithmetic computation tasks and math word problem task), and other cognitive tasks as their general cognitive abilities were observed as covariates. A series of hierarchical regression analyses showed that after controlling for age, gender, nonverbal matrix reasoning, and visual tracking, subitizing comparison (subitizing vs. subitizing, subitizing vs. estimation) still contributed to simple addition or simple subtraction but not to complex subtraction ability or math word problem. After taking form perception as an additional control variable, the predictive power of different dot comparison conditions disappeared. A path model also showed that form perception fully mediates the relation between numerosity comparison (within and beyond the subitizing range) and arithmetic performance. These findings support the claim that form perception is a non-numerical cognitive correlate of the relation between subitizing ability and math performance (especially arithmetic computation).

Risk Factors for Leptospirosis in Rural Communities of Bungoma County, Kenya: A Cross Sectional Survey

Leptospirosis is an important re-emerging zoonosis of worldwide public health concern. Leptospirosis is caused by a bacteria of the genus Leptospira. There was an outbreak of leptospirosis in humans in Bungoma County in 2004 with severe consequences. Leptospirosis is enzootic in cattle in Bungoma County. This study was conducted to determine the risk factors for leptospirosis in humans in Bungoma County. The risk factors considered in this study were; rainfall patterns, livestock management practices (grazing and watering system), home slaughter of livestock, consumption of un-inspected meat, rodent infestation in homes, and frequency of contact of livestock keepers with veterinary extension staff. A cross-sectional survey was carried out in Kimilili and Mt Elgon sub-counties of Bungoma County, Kenya. The study was conducted between April and July of 2017. The locations were then sampled, and 400 households selected using a systematic random sampling technique. Questionnaires were administered to heads of the identified households. Descriptive statistics and the chi-square test were used to analyze the data. Secondary data from medical records in Kimilili and Webuye health facilities were taken to show the disease trends in the year 2004. The study reveals the risk factors for leptospirosis in Bungoma County which include the close association of the community and their livestock (87.9%, n=400), rodent infestation in homes (92.3%, n=400), slaughter of animals in non-designated areas (83.8%, n=400), consumption of un-inspected meat (83.0%, n=400) and low contact of the population with veterinary extension staff (63.7%, n=400). The risk factors under consideration in this study were observed in over 80% of the study population. The study recommends that knowledge of leptospirosis and its risk factors be enhanced for effective control and prevention program.

Asiatic acid prevents glucocorticoid-induced femoral head osteonecrosis via PI3K/AKT pathway

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) represents a predominant etiology of non-traumatic osteonecrosis, imposing substantial pain, restricting hip mobility, and diminishing overall quality of life for affected individuals. Centella asiatica (L.) Urb. (CA), an herbal remedy deeply rooted in traditional oriental medicine, has exhibited noteworthy therapeutic efficacy in addressing inflammation and facilitating wound healing. Drawing from CA's historical applications, its anti-inflammatory, anti-apoptotic, and antioxidant attributes may hold promise for managing GIONFH. Asiatic acid (AA), a primary constituent of CA, has been substantiated as a key contributor to its anti-apoptotic, antioxidant, and anti-inflammatory capabilities, showcasing a close association with orthopedic conditions.For the investigation of whether AA could alleviate GIONFH through suppressing oxidative stress, apoptosis, and to delve into its potential cellular and molecular mechanisms, the connection between AA and disease was analyzed through network pharmacology. DEX-induced apoptosis in rat osteoblasts and GIONFH in rat models, got utilized for the verification in vitro/vivo, on underlying mechanism of AA in GIONFH. Network pharmacology analysis reveals a robust correlation between AA and GIONFH in multiple target genes. AA has demonstrated the inhibition of DEX-induced osteoblast apoptosis by modulating apoptotic factors like BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9. Furthermore, it effectively diminishes the ROS overexpression and regulates oxidative stress through mitochondrial pathway. Mechanistic insights suggest that AA's therapeutic effects involve phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) pathway activation. Additionally, AA has exhibited its potential to ameliorate GIONFH progression in rat models. Our findings revealed that AA mitigated DEX-induced osteoblast apoptosis and oxidative stress through triggering PI3K/AKT pathway. Also, AA can effectively thwart GIONFH occurrence and development in rats.

Impact of Environmental Food Intake on the Gut Microbiota of Endangered Père David's Deer: Primary Evidence for Population Reintroduction.

Reintroduction has been successful in re-establishing several endangered wild animals in their historical habitats, including Père David's deer (Elaphurus davidianus). Continuous monitoring of reintroduced individuals is essential for improving the sustainability of ex situ conservation efforts. Despite an increased recognition of the significance of the gut microbiome for animal health, the correlation between diet and the gut microbiome in E. davidianus is unclear. In this study, 15 fresh fecal samples of E. davidianus were collected from Tianjin Qilihai Wetland and the association between dietary and gut microbiota composition was evaluated. Microscopic observations showed that Nymphoides peltata [relative density (RD = 0.3514), Phragmites australis (RD = 0.2662), Setaria viridis (RD = 0.1211), and Typha orientalis (RD = 0.1085) were the main dietary plants in the fecal samples. High-throughput 16S rRNA sequencing showed a predominance of the phyla Firmicutes and Proteobacteria and the genus Psychrobacillus (26.53%) in the gut microbiota. The RD of N. peltata was significantly positively correlated with the abundance of Firmicutes (p = 0.005) and the genus UCG-005 (p = 0.024). This study indicates a close association between food digestion and nutrient intake, providing basic monitoring data for the full reintroduction and recovery of wild E. davidianus.

Diagnostic value of high frequency oscillation in localization of type Ⅱ focal cortical dysplasia epilepsy

Retrospective analysis was conducted on 9 patients with type Ⅱ focal cortical dysplasia (FCD) who underwent stereo-electroencephalography (SEEG) implantation in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from November 2020 to February 2023. The onset area, onset time, and frequency of high-frequency oscillations (HFO) were analyzed and the correlation of HFOs with interictal, preictal, and ictal periods. SEEG recordings of 80-500 Hz HFOs were observed in both interictal and ictal periods in 9 patients, with 6 patients exhibiting fast ripples (FR) in the range of 250-500 Hz. Surgical resection of the seizure onset area and FR-generating electrodes was performed, and postoperative follow-up for over 2 years indicated Engel I in 5 cases. 6 patients showed continuous discharge during the preictal period, and the distribution index of continuous discharge was positively correlated with seizure frequency. HFOs in the range of 80-500 Hz were present in all four seizure onset patterns during the ictal period. The onset area and FR-emitting electrode were surgically removed in 6 patients with continuous discharge and overlapping HFOs during the preictal period, with 5 cases of Engel I. Type Ⅱ FCD discharges exhibited complexity, high discharge indices, and a close association with HFOs. Compared with the spike wave, the electrode range of HF is more limited, and the incidence of HF before attack is significantly increased, which is closely correlated with the onset area. The simultaneous occurrence of HFO and the spike waves has higher diagnostic value than the individual occurrence, effectively enhancing surgical efficacy.

Recent Progress in Enzymatic Preparation of Chitooligosaccharides with a Single Degree of Polymerization and Their Potential Applications in the Food Sector.

Chitosan oligosaccharides (COS), derived from chitin, have garnered considerable attention owing to their diverse biological activities and potential applications. Previous investigations into the bioactivity of COS often encountered challenges, primarily stemming from the use of COS mixtures, making it difficult to discern specific effects linked to distinct degrees of polymerization (DP). Recent progress underscores the significant variation in the biological activities of COS corresponding to different DPs, prompting dedicated research towards synthesizing COS with well-defined polymerization. Among the available methods, enzymatic preparation stands out as a viable and environmentally friendly approach for COS synthesis. This article provides a comprehensive overview of emerging strategies for the enzymatic preparation of single COS, encompassing protein engineering, enzymatic membrane bioreactors, and transglycosylation reactions. Furthermore, the bioactivities of single COS, including anti-tumor, antioxidant, antibacterial, anti-inflammatory, and plant defense inducer properties, exhibit close associations with DP values. The potential applications of single COS, such as in functional food, food preservation, and crop planting, are also elucidated.

Intestinal mucosal barrier: a potential target for traditional Chinese medicine in the treatment of cardiovascular diseases.

Cardiovascular disease (CVD) is a serious public health problem, and among non-communicable diseases, CVD is now the leading cause of mortality and morbidity worldwide. CVD involves multiple organs throughout the body, especially the intestinal tract is the first to be involved. The impairment of the intestinal mucosal barrier is considered a significant pathological alteration in CVD and also contributes to the accelerated progression of the disease, thereby offering novel insights for CVD prevention and treatment. The treatment of Chinese medicine is characterized by multi-metabolites, multi-pathways, and multi-targets. In recent years, the studies of Traditional Chinese Medicine (TCM) in treating CVD by repairing the intestinal mucosal barrier have gradually increased, showing great therapeutic potential. This review summarizes the studies related to the treatment of CVD by TCM (metabolites of Chinese botanical drugs, TCM formulas, and Chinese patent medicine) targeting the repair of the intestinal mucosal barrier, as well as the potential mechanisms. We have observed that TCM exerts regulatory effects on the structure and metabolites of gut microbiota, enhances intestinal tight junctions, improves intestinal dyskinesia, repairs intestinal tissue morphology, and preserves the integrity of the intestinal vascular barrier through its anti-inflammatory, antioxidant, and anti-apoptotic properties. These multifaceted attributes position TCM as a pivotal modulator of inhibiting myocardial fibrosis, and hypertrophy, and promoting vascular repairment. Moreover, there exists a close association between cardiovascular risk factors such as hyperlipidemia, obesity, and diabetes mellitus with CVD. We also explore the mechanisms through which Chinese botanical drugs impact the intestinal mucosal barrier and regulate glucose and lipid metabolism. Consequently, these findings present novel insights and methodologies for treating CVD.

Assessment of Different Indices as Predictors of Difficult Airway in Obese Patients.

Introduction Difficulties with tracheal intubation contribute to the morbidity and mortality associated with anesthesia. Suggested predictors for difficult airwayinclude, history of obstructive sleep apnea, high Mallampati score, elderly, male, short neck, and high Wilson score.However, none of these has high diagnostic accuracy particularly in obese population. Parameters used to quantify obesity such as Body Mass Index(BMI), mid arm circumference, skin fold thickness,etc. have not been used as independent predictors of difficult airway. This study has been designed to evaluate the accuracy of commonly used tools to assess difficult airway and to test other obesity markers as scale for assessing difficult airway i.e. Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3. Aim To assess BMI, Mallampati grading, Neck circumference and Thyromental distance as predictors of difficult airway in obese patients and to validate neck circumference to thyromental distance ratio and skin fold thickness as a tool for assessment of difficult airway (Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3.) in obese patients. Methods This prospective observational study was carried out on 51 obese patients (as per BMI) of ASA gradeII, either sex, aged 23 to 57 years posted for elective surgery under general anesthesia with endotracheal intubation. After subjective assessment of difficult airway following data sets and variables were obtained - sex, weight, height, body mass index (BMI),Modified Mallampati class (MPG), Cormack-Lehane (CL) grade, adequacy of bag mask ventilation (BMV), number of endotracheal intubation attempts, patient's neck circumference (NC), thyromental distance (TMD), waist-hip ratio (WHR) and Skin fold thickness. The observations made during the study were statistically analyzed and correlated as predictors for difficult airway. Result Correlation of MPG to CL-grade (r-0.41, p-0.003), BMV (r-0.31, p-0.028) & No. of intubationattempts (r-0.37, p-0.007) was mild & statistically significant. Correlation of Neck Circumference with CL-grade (r-0.57, p-0.000), & No. of intubation attempts (r-0.62, p-0.000), found moderate & statistically significant, & with BMV was mild and statistically significant (r-0.48, p-0.000). Correlation of Thyromental Distance to CL-grade (r-0.65, p-0.000), BMV (r-0.70, p-0.000) & No. of intubationattempts (r-0.61, p-0.000) was moderate & statistically significant. Correlation of BMI to CL-grade (r-0.11, p-0.428), BMV (r-0.04, p-0.757) & No. of intubation attempts (r-0.16, p-0.257) was weak & not significant. Skin Fold Thickness showed no significant association with Difficult airway i.e., CL Grade (p-0.478), BMV (p-0.101), and No. of intubation attempts (p-0.143). Correlation of NC/TMD ratio with BMV (r-0.74, p-0.000), CL-grade (r-0.76, p-0.000), & No. of intubation attempts (r-0.77, p-0.000) wasmoderate & statistically significant. Conclusion NC, TMDand NC/TMD Ratio depicted a close association with airway difficulty in obese patients. Obesity grade is a risk factor for difficult airway but predictors of obesity including Skin Fold Thickness, individually did not showassociation with difficult airway (small sample size may be a limiting factor). None of the commonly performed tests alone has proven to be adequate in predicting difficult intubation in the obese population.

Diurnal variation in short‐ and long‐duration precipitation within the Dabie Mountain region in Central China

AbstractDiurnal variation in regional precipitation in Central and East China has been broadly identified in previous study. This study focused on clarifying not only the differences in the diurnal variation concerning the local precipitation occurred in the Dabie Mountain (DBM) region and the regional precipitation occurred through the middle‐lower reaches of the Yangtze River Basin, but also the association mechanism between diurnal variation in local precipitation with differing duration and diurnal modulation of ambient circulations driven by large‐scale background synoptic force or local‐scale orographic force of the DBM. It was found that cases of short duration precipitation (SDP, duration <6 h) and cases of long duration precipitation (LDP, duration ≥6 h) exhibit vastly different patterns of diurnal variations. Further investigation revealed that the primary pattern of the ambient circulation responsible for SDP and LDP is the recycling transformation between a closed cyclonic circulation to a cyclonic wind shear, and the recycling movement of a closed cyclonic circulation in the lower troposphere respectively. Although the diurnal variation in LDP exhibited greater orographic regional differences between the west slope (WS) region and the east slope (ES) region in comparison with that of SDP, topographical sensitivity experiments of the DBM and detailed analysis of background synoptic systems associated with LDP indicated that this regional orographic difference shows closer association with eastward propagation of background synoptic systems than orographic effects of the DBM. Respective strengthening of upward vertical motion at different levels of the troposphere during diurnal variation in SDP and LDP cases provide substantial evidences to reconfirm the close association with orographic force in lower the troposphere for SDP cases and background synoptic force in middle troposphere for LDP cases. Further quantitative diagnosis also confirmed that the orographic effects of the DBM is conducive to cause marked differences in the diurnal variation in SDP cases between the WS region and the ES region via adjustment of the upslope wind over the former and the circumventing wind over the latter.

Metabarcoding study to reveal the structural community of strongylid nematodes in domesticated horses in Thailand

BackgroundMixed strongylid infections significantly impact equine health and performance. Traditional microscopy-based methods exhibit limitations in accurately identifying strongylid species. Nemabiome deep amplicon sequencing approach previously succeeded in describing the strongylid communities in livestock including equids. However, there are no available studies that describe the structural communities of strongylid parasites in horses in Thailand. Therefore, this study was undertaken encompassing the ITS-2 rDNA metabarcoding assay to characterize strongylid species within horse fecal samples collected from a cohort of yearlings at the largest domesticated stud farm in Thailand. In addition, to investigate the capability of ITS-2 rDNA in assessing the phylogenetic relationships among the identified strongylid species.ResultsThe study identified 14 strongylid species in the examined equine populations, each with varying prevalence. Notably, Cylicocyclus nassatus and Cylicostephanus longibursatus were identified as the predominant species, with Strongylus spp. conspicuously absent. The phylogenetic analysis of 207 amplicon sequence variants (ASVs) displayed a complex relationship among the investigated cyathostomin species, with some species are positioned across multiple clades, demonstrating close associations with various species and genera.ConclusionThe ITS-2 nemabiome sequencing technique provided a detailed picture of horse strongylid parasite species in the studied population. This establishes a foundation for future investigations into the resistance status of these parasites and enables efforts to mitigate their impact.

RNA interference confirmed a close association of CYP, ApD, and UCH with the function of CpG ODNs in Litopenaeus vannamei

CpG oligonucleotides (CpG ODNs) have been demonstrated to enhance the innate immune response in various organisms, including Litopenaeus vannamei, a species of significant economic importance. However, the precise mechanism or the genetic factors of CpG ODNs underlying function in L. vannamei remained elusive. Our previous experiment has identified five potential marker genes, including cytochrome P450 (CYP), gamma-butyrobetaine dioxygenase (γ-BDO), apolipoprotein D (ApD), prostaglandin reductase 1 (PGR1), and ubiquitin carboxyl-terminal hydrolase (UCH). In this study, RNA interference (RNAi) was employed to validate the relevance of these five genes in responding the stimulation of CpG ODNs. Briefly, shrimps were fed CpG ODNs and subsequently injected dsRNA targeting these five genes for interference. Finally, the non-specific immune parameters of shrimps, including the expression of immune-related genes and antioxidant capacity of hepatopancreas, as well as the mortality of shrimps after pathogen attack were assessed. The tissue distribution analysis revealed a high abundance of CYP in the hepatopancreas, γ-BDO in the hemocytes, ApD in the eyestalk, PGR1 in the hemocytes, and UCH in the gonad. After blocking CYP, ApD, and UCH through RNAi, a significant down-regulation of the mRNA expression levels of immune-related genes, including ALF, TNF-α, Toll, and TOR, was observed. Additionally, a notable decline in the activity of antioxidant enzymes, such as CAT, GPX, GST, and SOD, was also observed. Moreover, the mortality rates of shrimps in the CYP, ApD, and UCH inhibited groups significantly increased compared to other treatment groups following exposure to Vibrio parahaemolyticus causing acute hepatopancreatic necrosis disease (VpAHPND) and white spot syndrome virus (WSSV). These results collectively suggest a close association of CYP, ApD, and UCH with the function of CpG ODNs in shrimps which will provide significant theoretical insights into comprehending the mechanism of CpG ODNs and optimizing their practical application in shrimp's aquaculture.

Precision Medicine for Nasopharyngeal Cancer-A Review of Current Prognostic Strategies.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) driven malignancy arising from the nasopharyngeal epithelium. Current treatment strategies depend on the clinical stage of the disease, including the extent of the primary tumour, the extent of nodal disease, and the presence of distant metastasis. With the close association of EBV infection with NPC development, EBV biomarkers have shown promise in predicting treatment outcomes. Among the omic technologies, RNA and miRNA signatures have been widely studied, showing promising results in the research setting to predict treatment response. The transformation of radiology images into measurable features has facilitated the use of radiomics to generate predictive models for better prognostication and treatment selection. Nonetheless, much of this work remains in the research realm, and challenges remain in clinical implementation.

Divergence in toxin antigenicity and venom enzymes in Tityus melici, a medically important scorpion, despite transcriptomic and phylogenetic affinities with problematic Brazilian species

The Brazilian scorpion Tityus melici, native to Minas Gerais and Bahia, is morphologically related to Tityus serrulatus, the most medically significant species in Brazil. Despite inhabiting scorpion-envenomation endemic regions, T. melici venom remains unexplored. This work evaluates T. melici venom composition and function using transcriptomics, enzymatic activities, and in vivo and in vitro immunological analyses. Next-Generation Sequencing unveiled 86 components putatively involved in venom toxicity: 39 toxins, 28 metalloproteases, seven disulfide isomerases, six hyaluronidases, three phospholipases and three amidating enzymes. T. serrulatus showed the highest number of toxin matches with 80–100 % sequence similarity. T. melici is of medical importance as it has a venom LD50 of 0.85 mg/kg in mice. We demonstrated venom phospholipase A2 activity, and elevated hyaluronidase and metalloprotease activities compared to T. serrulatus, paralleling our transcriptomic findings. Comparison of transcriptional levels for T. serrulatus and T. melici venom metalloenzymes suggests species-specific expression patterns in Tityus. Despite close phylogenetic association with T. serrulatus inferred from COI sequences and toxin similarities, partial neutralization of T. melici venom toxicity was achieved when using the anti-T. serrulatus antivenom, implying antigenic divergence among their toxins. We suggest that the Brazilian therapeutic scorpion antivenom could be improved to effectively neutralize T. melici venom.

Comparative analysis of emotional facial expression recognition and empathy in children with prader-willi syndrome and autism spectrum disorder

BackgroundPrader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder that is often comorbid with Autism Spectrum Disorder (ASD). Due to the close association between these two conditions, and recognizing that Theory of Mind (ToM) is related to social behaviors in ASD, there is a growing interest in studying the reciprocity of social communication between these two groups.MethodThe primary objective of this study was to compare how children (n = 45) with PWS (n = 15), ASD (n = 15), and a control group (n = 15) respond to emotion recognition of facial expressions and empathy, which are both concepts related to ToM. The study utilized two tools named FEEL and Deusto-e-Motion 1.0. We also evaluated the Working Memory index of the WISC-IV scale, the Social Perception domain of the NEPSY-II battery, and the SCQ in both clinical groups.ResultsOur findings suggest that individuals with PWS exhibit lower accuracy in recognizing facial expressions and empathy compared to the control group. Both clinical groups exhibited a delayed reaction time compared to the control group. Children with PWS display difficulties in recognizing emotions of disgust and surprise. In terms of cognitive empathy, children with PWS showed a greater inclination to respond to disgust as compared to children with ASD.ConclusionsThis study represents the initial stage in comprehending the emotional and empathetic abilities of children with PWS and ASD. The findings can provide valuable insights for developing future interventions.

Pig pangenome graph reveals functional features of non-reference sequences

BackgroundThe reliance on a solitary linear reference genome has imposed a significant constraint on our comprehensive understanding of genetic variation in animals. This constraint is particularly pronounced for non-reference sequences (NRSs), which have not been extensively studied.ResultsIn this study, we constructed a pig pangenome graph using 21 pig assemblies and identified 23,831 NRSs with a total length of 105 Mb. Our findings revealed that NRSs were more prevalent in breeds exhibiting greater genetic divergence from the reference genome. Furthermore, we observed that NRSs were rarely found within coding sequences, while NRS insertions were enriched in immune-related Gene Ontology terms. Notably, our investigation also unveiled a close association between novel genes and the immune capacity of pigs. We observed substantial differences in terms of frequencies of NRSs between Eastern and Western pigs, and the heat-resistant pigs exhibited a substantial number of NRS insertions in an 11.6 Mb interval on chromosome X. Additionally, we discovered a 665 bp insertion in the fourth intron of the TNFRSF19 gene that may be associated with the ability of heat tolerance in Southern Chinese pigs.ConclusionsOur findings demonstrate the potential of a graph genome approach to reveal important functional features of NRSs in pig populations.

Two Novel Betarhabdovirins Infecting Ornamental Plants and the Peculiar Intracellular Behavior of the Cytorhabdovirus in the Liana Aristolochia gibertii.

Two novel members of the subfamily Betarhabdovirinae, family Rhabdoviridae, were identified in Brazil. Overall, their genomes have the typical organization 3'-N-P-P3-M-G-L-5' observed in mono-segmented plant-infecting rhabdoviruses. In aristolochia-associated cytorhabdovirus (AaCV), found in the liana aristolochia (Aristolochia gibertii Hook), an additional short orphan ORF encoding a transmembrane helix was detected between P3 and M. The AaCV genome and inferred encoded proteins share the highest identity values, consistently < 60%, with their counterparts of the yerba mate chlorosis-associated virus (Cytorhabdovirus flaviyerbamate). The second virus, false jalap virus (FaJV), was detected in the herbaceous plant false jalap (Mirabilis jalapa L.) and represents together with tomato betanucleorhabdovirus 2, originally found in tomato plants in Slovenia, a tentative new species of the genus Betanucleorhabdovirus. FaJV particles accumulate in the perinuclear space, and electron-lucent viroplasms were observed in the nuclei of the infected cells. Notably, distinct from typical rhabdoviruses, most virions of AaCV were observed to be non-enclosed within membrane-bounded cavities. Instead, they were frequently seen in close association with surfaces of mitochondria or peroxisomes. Unlike FaJV, AaCV was successfully graft-transmitted to healthy plants of three species of the genus Aristolochia, while mechanical and seed transmission proved unsuccessful for both viruses. Data suggest that these viruses belong to two new tentative species within the subfamily Betarhabdovirinae.

T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma-A Systematic Review.

Cutaneous squamous cell carcinoma (cSCC) is an invasive malignancy that disproportionately afflicts immunosuppressed individuals. The close associations of cSCC with immunosuppression and human papillomavirus (HPV) infection beget the question of how these three entities are intertwined in carcinogenesis. By exploring the role of T cell immunity in HPV-related cSCC based on the existing literature, we found that the loss of T cell immunity in the background of β-HPV infection promotes cSCC initiation following exposure to environmental carcinogens or chronic trauma. This highlights the potential of developing T-cell centred therapeutic and preventive strategies for populations with increased cSCC risk.

Development of a necroptosis-related prognostic model for uterine corpus endometrial carcinoma

Necroptosis is a recently identified caspase-independent form of cell death which plays a significant role in the onset and progression of cancer. MicroRNAs (miRNAs) are vital for the development of uterine corpus endometrial carcinoma (UCEC) because they are an important regulatory component in necroptosis. This study developed a new necroptosis-related miRNAs profile to predict the prognosis of patients with UCEC. The TCGA-UCEC cohort’s RNA sequencing data, consisting of 534 tumor samples and 33 normal samples, was downloaded. Ten differentially expressed miRNAs related to necroptosis were identified. A prediction model for necroptosis-related miRNAs was then created through COX regression and nomograms analysis. Clinical and pathological parameters were integrated to construct a nomogram and evaluate the model. Prognosis-related miRNAs were further used to predict target genes, and functional analysis was conducted to explore the potential mechanisms of these target genes. Subsequently, immune infiltration analysis was performed using transcriptome data to identify immune genes associated with prognosis, and the expression levels of target gene was validated using UCEC tissues. We identified 7 up-regulated miRNAs (hsa-miR-577, hsa-miR-7-5p, hsa-miR-210-3p, hsa-miR-210-5p, hsa-miR-200a-5p, hsa-miR-141-3p, hsa-miR-425-5p) and 3 down-regulated miRNAs (hsa-miR-7-2-3p, hsa-miR-383-5p, hsa-miR-29a-3p). The risk signature was based on univariate and multivariate COX analyses, constructed using 2 independent prognostic factors and miRNAs (hsa-miR-425-5p, hsa-miR-7-5p) associated with necroptosis. Nomograms demonstrated the prognostic value of risk level, age, FIGO stage, and histological type. Kaplan–Meier analysis revealed significant differences in overall survival (OS) outcomes associated with the expression of hsa-miR-425-5p (P < 0.001) and hsa-miR-7-5p (P = 0.015). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations indicated that these miRNAs play crucial roles in tumor development, metastasis, and prognosis. Immune infiltration analysis showed decreased infiltration of CD8+ T cells, CD8+ T cells, NK cells, and M1 macrophages in normal tissues. Subsequently, a necroptosis-related immune gene significantly associated with prognosis (THRB) was identified, western blot and immunohistochemical staining confirmed the differential expression of THRB in normal endometrial tissues and tumor. Our findings demonstrate a close association between necroptosis and UCEC. The two necroptosis-related miRNAs used in this study may serve as valuable prognostic markers for UCEC patients, and are associated with immune cell infiltration. This suggests that necroptosis may be involved in the development of UCEC through its interaction with immune responses.

The causal relationship between depression and obstructive sleep apnea: A bidirectional Mendelian randomization study

ObjectiveNumerous studies have reported the close association of depression with obstructive sleep apnea (OSA). However, the causal nature and direction remain unclear. This study aimed to identify the genetic causal relationship between depression and OSA using Mendelian randomization (MR). MethodsBased on publicly available genome-wide association studies data of depression and OSA, we conducted a bidirectional two-sample MR study. The inverse-variance weighted (IVW) was used as the main analysis method. Moreover, multivariable MR was performed to further explore the underlying genetic causality of OSA and depression after adjusting for several potential mediators. ResultsThe univariable MR analysis revealed a significant causality of depression on the susceptibility of OSA (ORivw = 1.29, 95%CI:1.11,1.50; p < 0.001). This relationship was evidenced by the phenotypes for broad depression (ORivw = 3.30, 95%CI: 1.73, 6.29; p < 0.001), probable major depression (ORivw = 18.79, 95%CI: 5.69, 61.99; p < 0.001), and ICD-10 major depression (ORivw = 23.67, 95%CI: 4.13, 135.74; p < 0.001). In the reverse direction, no significant causal effect of OSA on depression was found. After adjusting for smoking, alcohol use, obesity, type 2 diabetes, insomnia, age, gender, and codeine, most of these results suggested that depression remained significantly and positively associated with OSA. ConclusionThese findings may contribute to the understanding of the etiology of depression and OSA and also suggest the clinical significance of controlling depression for the prevention of OSA.