A proposed novel digital condylar position adjustment technique to help restore a normal disc-condyle relationship.

Objectives: To demonstrate a novel digital technique that enables real-time visualisation of occlusal transfer and adjustment of condyle position, to (1) improve the repeatability of occlusal transfer and the accuracy of condyle position adjustment and (2) be clinically effective in helping to restore the disc-condyle relationship. Materials and methods: Three participants were included in the study and underwent facebow transfers using two different methods. The digital method used patient-related three-dimensional imaging data matched with digital dental casts for occlusal transfer. The conventional method used anatomical facebows. The condylar position was adjusted based on occlusal transfer results. The results were evaluated and compared in three dimensions. In addition, clinical application data from 36 patients were analysed before and after condylar position adjustment. Statistical significance was set at p < 0.05. Results: Differences in the spatial positions of the three anatomical structures reproduced by both methods were statistically significant (p = 0.000). After adjusting the rotation of the condylar position, the positional deviation of the condylar point along the X- and Z-axes was significantly lower in the digital group (p < 0.05). After adjustment for translation (X and Z), the positional deviation showed no difference along the X- and Z-axes (p > 0.05) but a significant difference along the Y-axis (p < 0.001). Conclusion: A novel digital technique for occlusal transfer and condylar position adjustment was presented. This technique simplifies clinical practice, improves the accuracy of results, and can help restore a normal disc-condyle relationship.

Association of early-term birth and breastfeeding practices with nutritional outcomes in singleton term infants: a multicenter cross-sectional study.

BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.

Effect of occlusal contact on TMJ loading during occlusion: An in silico study.

Alterations in occlusal features may have significant consequences, ranging from dental aesthetics to health issues. Temporomandibular joint disorders (TMDs) are often associated with joint overload, and the correlation between occlusal features and TMDs has been thoroughly discussed. In current work, we introduced a novel stomatognathic model that aligns well with in vivo experimental measurements, specifically designed to decouple the impact of occlusal contact and periodontal ligament (PDL) negative feedback on temporomandibular joint (TMJ) loading. Utilizing an in-silico approach, the simulation analysis included six symmetric occlusal contact scenarios. Furthermore, a biomechanical lever model was employed to clarify the mechanical mechanism and investigate the multi-factorial effects of TMJ overload. These findings indicate that anterior shifts in the occlusal centre lead to increased TMJ loading, particularly in occlusal contact cases with anteroposterior changes. Considering the symmetrical distribution of occlusal contact, mediolateral alterations had a more modest effect on TMJ loading. Additionally, potential negative feedback activated by principal strain of periodontal could not only alleviate joint load but also diminish occlusal force. These investigations enhance our understanding of the intricate interactions between masticatory muscles, occlusal forces, and joint contact forces, thereby providing motivation for future comprehensive studies on TMJ biomechanical overload.

A materials terminology knowledge graph automatically constructed from text corpus.

A scalable, reusable, and broad-coverage unified material knowledge representation shows its importance and will bring great benefits to data sharing among materials communities. A knowledge graph (KG) for materials terminology, which is a formal collection of term entities and relationships, is conceptually important to achieve this goal. In this work, we propose a KG for materials terminology, named Materials Genome Engineering Database Knowledge Graph (MGED-KG), which is automatically constructed from text corpus via natural language processing. MGED-KG is the most comprehensive KG for materials terminology in both Chinese and English languages, consisting of 8,660 terms and their explanations. It encompasses 11 principal categories, such as Metals, Composites, Nanomaterials, each with two or three levels of subcategories, resulting in a total of 235 distinct category labels. For further application, a knowledge web system based on MGED-KG is developed and shows its great power in improving data sharing efficiency from the aspects of query expansion, term, and data recommendation.

Cost-Effectiveness of Screening Asymptomatic Carotid Stenosis by Atherosclerotic Cardiovascular Risk.

Importance: Extracranial internal carotid artery stenosis (50-99% arterial narrowing) is an important risk factor for ischemic stroke. Yet, the benefits and harms of targeted screening for asymptomatic carotid artery stenosis (ACAS) have not been assessed in population-based studies. Objective: To estimate the cost-effectiveness of one-time, targeted ACAS screening stratified by atherosclerotic cardiovascular disease (ASCVD) risk using the American Heart Association's Pooled Cohort Equations. Design Setting and Participants: We developed a lifetime microsimulation model of ACAS and stroke for a hypothetical cohort representative of US adults aged 50-80 years without stroke history. We used the Cardiovascular Health Study to estimate the probability and severity of ACAS based on individual characteristics (e.g., age, sex, smoking status, blood pressure, and cholesterol). Stroke risks were functions of these characteristics and ACAS severity. In the model, individuals testing positive for >70% stenosis with Duplex ultrasound and a confirmatory diagnostic test undergo revascularization, which may reduce the risk of stroke but also introduces complication risks. Diagnostic performance parameters, revascularization benefits and risks, utility weights, and costs were estimated from published sources. Cost-effectiveness was assessed from the health care sector perspective using a $100,000/quality-adjusted life year (QALY) threshold. Main Outcomes and Measures: Estimated stroke events prevented, lifetime costs, QALYs, and incremental cost-effectiveness ratios (ICERs) associated with ACAS screening. Costs (2023 USD) and QALYs were discounted at 3% annually. Results: We found that screening individuals with a 10-year ASCVD risk >30% was the most cost-effective strategy, with an ICER of $89,000/QALY. This strategy would make approximately 11.9% of the population eligible for screening, averting an estimated 24,084 strokes. Results were sensitive to variations in the efficacy and complication risk of revascularization. In probabilistic sensitivity analysis, screening those in lower ASCVD risk groups (0-20%) only had a 0.6% chance of being cost-effective. Conclusion and Relevance: A one-time screening may only be cost-effective for adults at a relatively high ASCVD risk. Our findings provide a framework that can be adapted as future clinical trial data continue to improve our understanding of the role of revascularization and intensive medical therapy in contemporary stroke prevention secondary to carotid disease.

Evaluation of modified clear Twin Block aligner in treating adolescents with skeletal class II malocclusion: A two-centre cephalometric study.

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

Effects of aerobic exercise on children's executive function and academic performance: A systematic review and meta-analysis.

Objective: To investigate the effects of exercise on executive function in children, providing an evidence-based foundation to inform future research in school physical education and health education. Methods: We searched ten databases: Cochrane Library, Scopus, OVID, Web of Science, PubMed, EBSCOhost, SPORTDiscus, PsycINFO, CNKI, WANFANG DATA, VIP, and SinoMed, and eight articles were included. Applying the revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2), funnel plots and Egger regression analysis were integrated with R meta-analysis to screen for publication bias. The quality of the evidence was appraised using the Grading system. Results: The included literature contained 2655 participants, with 1308 in the experimental group and 1347 in the control group. The results indicated that the aerobic exercise group considerably improved inhibitory control in children compared to the control group [SMD = 0.29, 95% CI (0.05, 0.54), P = 0.018]; working memory [SMD = 0.25, 95% CI (0.07, 0.42), P = 0.005]; and cognitive flexibility [SMD = 0.36, 95% CI (0.17, 0.54), P < 0.001]. However, the findings indicated that only aerobic exercise interventions extending beyond 50 weeks positively influenced academic performance in children [SMD = 1.19, 95% CI (0.34, 2.04), P = 0.006]. The results of an Egger regression analysis revealed that the p-values for inhibitory control, working memory, cognitive flexibility, and academic performance were more significant than 0.1. The Grade system said that the quality of evidence was all low regarding the level of evidence. Conclusion: Aerobic exercise enhanced executive function but only aerobic exercise interventions extending beyond 50 weeks demonstrated a significant effect on the academic performance of children. Due to the low quality of evidence presented in this study, additional high-quality randomized controlled trials are needed to confirm these findings.

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model.

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß, and MCP-1) while increasing T cells (CD3+, CD4+, and CD8+) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

The hidden risk: Changes in functional potentials of microbial keystone taxa under global climate change jeopardizing soil carbon storage in alpine grasslands.

Climate change is endangering the soil carbon stock of alpine grasslands on the Qinghai-Tibetan Plateau (QTP), but the limited comprehension regarding the mechanisms that sustain carbon storage under hydrothermal changes increases the uncertainty associated with this finding. Here, we examined the relative abundance of soil microbial keystone taxa and their functional potentials, as well as their influence on soil carbon storage with increased precipitation across alpine grasslands on the QTP, China. The findings indicate that alterations in precipitation significantly decreased the relative abundance of the carbon degradation potentials of keystone taxa, such as chemoheterotrophs. The inclusion of keystone taxa and their internal functional potentials in the two best alternative models explained 70% and 63% of the variance in soil organic carbon (SOC) density, respectively. Moreover, we found that changes in chemoheterotrophs had negative effects on SOC density as indicated by a structural equation model, suggesting that some specialized functional potentials of keystone taxa are not conducive to the accumulation of carbon sink. Our study offers valuable insights into the intricate correlation between precipitation-induced alterations in soil microbial keystone taxa and SOC storage, highlighting a rough categorization is difficult to distinguish the hidden threats and the importance of incorporating functional potentials in SOC storage prediction models in response to changing climate.

SP-CHAP, an endolysin with enhanced activity against biofilm pneumococci and nasopharyngeal colonization.

Streptococcus pneumoniae (Spn), a Gram-positive bacterium, is responsible for causing a wide variety of invasive infections. The emergence of multi-drug antibiotic resistance has prompted the search for antimicrobial alternatives. Phage-derived peptidoglycan hydrolases, known as endolysins, are an attractive alternative. In this study, an endolysin active against Spn, designated SP-CHAP, was cloned, produced, purified, biochemically characterized, and evaluated for its antimicrobial properties. Cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains are widely represented in bacteriophage endolysins but have never previously been reported for pneumococcal endolysins. Here, we characterize the first pneumococcal endolysin with a CHAP catalytic domain. SP-CHAP was antimicrobial against all Spn serovars tested, including capsular and capsule-free pneumococci, and it was found to be more active than the most widely studied pneumococcal endolysin, Cpl-1, while not affecting various oral or nasal commensal organisms tested. SP-CHAP was also effective in eradicating Spn biofilms at concentrations as low as 1.56 µg/mL. In addition, a Spn mouse nasopharyngeal colonization model was employed, which showed that SP-CHAP caused a significant reduction in Spn colony-forming units, even more than Cpl-1. These results indicate that SP-CHAP may represent a promising alternative to combating Spn infections. IMPORTANCE: Considering the high rates of pneumococcal resistance reported for several antibiotics, alternatives are urgently needed. In the present study, we report a Streptococcus pneumoniae-targeting endolysin with even greater activity than Cpl-1, the most characterized pneumococcal endolysin to date. We have employed a combination of biochemical and microbiological assays to assess the stability and lytic potential of SP-CHAP and demonstrate its efficacy on pneumococcal biofilms in vitro and in an in vivo mouse model of colonization. Our findings highlight the therapeutic potential of SP-CHAP as an antibiotic alternative to treat Streptococcus pneumoniae infections.

Relationships between functional temporomandibular joint space and disc morphology, position, and condylar osseous condition in patients with temporomandibular disorder.

OBJECTIVE: To investigate the correlations between joint space and temporomandibular joint (TMJ) components and the compressive states of the disc and condyle subsequent to joint space changes. MATERIALS AND METHODS: A total of 240 TMJs were categorized according to disc morphology, disc position, and condylar osseous condition. The two-dimensional (2D) and three-dimensional (3D) measurements were compared. The functional joint space (FJS) and disc areas on closed- and open-mouth images (DA-C and DA-O) were also calculated, and the joint space was measured in five directions. Different groups of TMJ components were compared. A spring model was used to simulate the effect of condylar displacement on the disc and condyle. RESULTS: Disc morphology was strongly correlated with its position. The measurements were equivalent between 2D and 3D methods. DA-C and FJS differed significantly between groups. The DA-C to FJS ratio differed between the Class 2 and Class 3 groups and between disc displacement groups with and without reduction. Altered disc morphology and position were correlated with significant changes in joint space in the 60°, 90°, and 120° directions. Despite minor discrepancies among condylar osseous conditions, reduced joint space was correlated with bone destruction at the corresponding site. The spring model stimulation revealed that condylar displacement caused elevated stresses on the disc and condyle. CONCLUSIONS: Condylar displacement causes joint space alterations while exerting compressive pressure on both the disc and condyle. CLINICAL RELEVANCE: Proper condylar positioning within the fossa is recommended to ensure sufficient articular disc accommodation.

A Girl with PRRT2 Mutation Presenting with Benign Familial Infantile Seizures Followed by Autistic Regression.

Benign familial infantile seizure (BFIS) is an autosomal dominant infantile-onset epilepsy syndrome with a typically benign prognosis. It is commonly associated with heterozygous mutations of the PRRT2 gene located on chromosome 16p11.2. The frameshift heterozygous mutation (c.649dupC, p.Arg217Profs∗8) in PRRT2 is responsible for the majority of BFIS cases. In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype-phenotype heterogeneity in PRRT2 mutations. This clinical observation highlights the possibility that BFIS patients with PRRT2 mutations may not always have a benign neurodevelopmental prognosis, emphasizing the need for long-term clinical follow-up.

Screening and Bioinformatics Analysis of Differential Genes in Autism Spectrum Disorder Based on GEO Database.

OBJECTIVE: The prevalence of autism spectrum disorder (ASD) in children has been increasing year by year, which has seriously affected the quality of life of children. There are many theories about the cause of ASDs, with some studies suggesting that it may be related to gene expression levels or inflammation and immune system dysfunction. But the exact mechanism is not fully understood. METHODS: profile of gene expression The protein interaction network (PPI) of differentially expressed genes was created using the STRING web tool and GSE77103, which was chosen from the gene expression omnibus (GEO) database. Using the CytoHubba plugin of Cytoscape program, the hub genes were examined. The hub gene regulatory network for miRNA-mRNA was then built. RESULTS: We identified 551 differentially expressed genes(DEGs) in 8 children with ASD and normal children. In addition, we screened out 10 hub genes (MX1, ISG15, IRF7, DDX58, IFIT1, BCL2L1, HPGDS, CTSD, PTGS2 and CD68) that were most associated with the development of ASDs. Then, microRNAs (miRNAs) closely related to hub genes (such as has-miR-27a-5p) were screened, and the miRNA-mRNA regulatory network was constructed. CONCLUSION: In this study, a total of 10 hub genes were identified, including MX1, ISG15, IRF7, DDX58, IFIT1, BCL2L1, HPGDS, CTSD, PTGS2 and CD68, which are closely related to ASD. These genes may play a key role in the occurrence and progression of ASD. In addition, we also revealed some miRNAs that regulate the hub genes of ASD. These results may deepen our understanding of ASD and provide potential biomarkers and targets for future treatment of patients with ASD.

Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation.

IMPORTANCE: Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can "win" by taking over the host, or the bacteria can "lose" if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that "activate" innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

Framework for determining the optimal course of action when efficiency and affordability measures differ by perspective in cost-effectiveness analysis-with an illustrative case of HIV treatment in Mozambique.

BACKGROUND: Cost-effectiveness analysis (CEA) is a standard tool for evaluating health programs and informing decisions about resource allocation and prioritization. Most CEAs evaluating health interventions in low- and middle-income countries adopt a health sector perspective, accounting for resources funded by international donors and country governments, while often excluding out-of-pocket expenditures and time costs borne by program beneficiaries. Even when patients' costs are included, a companion analysis focused on the patient perspective is rarely performed. We view this as a missed opportunity. METHODS: We developed methods for assessing intervention affordability and evaluating whether optimal interventions from the health sector perspective also represent efficient and affordable options for patients. We mapped the five different patterns that a comparison of the perspective results can yield into a practical framework, and we provided guidance for researchers and decision-makers on how to use results from multiple perspectives. To illustrate the methodology, we conducted a CEA of six HIV treatment delivery models in Mozambique. We conducted a Monte Carlo microsimulation with probabilistic sensitivity analysis from both patient and health sector perspectives, generating incremental cost-effectiveness ratios for the treatment approaches. We also calculated annualized patient costs for the treatment approaches, comparing the costs with an affordability threshold. We then compared the cost-effectiveness and affordability results from the two perspectives using the framework we developed. RESULTS: In this case, the two perspectives did not produce a shared optimal approach for HIV treatment at the willingness-to-pay threshold of 0.3 × Mozambique's annual GDP per capita per DALY averted. However, the clinical 6-month antiretroviral drug distribution strategy, which is optimal from the health sector perspective, is efficient and affordable from the patient perspective. All treatment approaches, except clinical 1-month distributions of antiretroviral drugs which were standard before Covid-19, had an annual cost to patients less than the country's annual average for out-of-pocket health expenditures. CONCLUSION: Including a patient perspective in CEAs and explicitly considering affordability offers decision-makers additional insights either by confirming that the optimal strategy from the health sector perspective is also efficient and affordable from the patient perspective or by identifying incongruencies in value or affordability that could affect patient participation.

Divergent sequences of tetraspanins enable plants to specifically recognize microbe-derived extracellular vesicles.

Extracellular vesicles (EVs) are important for cell-to-cell communication in animals. EVs also play important roles in plant-microbe interactions, but the underlying mechanisms remain elusive. Here, proteomic analyses of EVs from the soybean (Glycine max) root rot pathogen Phytophthora sojae identify the tetraspanin family proteins PsTET1 and PsTET3, which are recognized by Nicotiana benthamiana to trigger plant immune responses. Both proteins are required for the full virulence of P. sojae. The large extracellular loop (EC2) of PsTET3 is the key region recognized by N. benthamiana and soybean cells in a plant receptor-like kinase NbSERK3a/b dependent manner. TET proteins from oomycete and fungal plant pathogens are recognized by N. benthamiana thus inducing immune responses, whereas plant-derived TET proteins are not due to the sequence divergence of sixteen amino acids at the C-terminal of EC2. This feature allows plants to distinguish self and non-self EVs to trigger active defense responses against pathogenic eukaryotes.

Identification of target hub genes and construction of a novel miRNA regulatory network in autism spectrum disorder by integrated analysis.

The incidence of autism spectrum disorder (ASD) is increasing year by year in children. The aim of the study was to find possible biomarkers for ASD diagnosis as well as examine MicroRNA (miRNA) signatures and crucial pathways. We conducted a two-stage study to explore potential target genes and functional miRNAs. Peripheral blood samples of children with ASD were enrolled and performed RNA sequencing analysis. The overlapped candidate genes were further screened in combination with differentially expressed genes (DEGs) of GSE77103 datasets. STRING established a protein-protein interaction network comprising DEGs. The hub genes were filtered out using the CytoHubba. Then, we set up a miRNA-mRNA regulatory network. Correlational analyses between hub genes and immune cells associated with ASD were carried out using the CIBERSORT software to assess the diversity of immune cell types in ASD. RNA-sequencing analysis was used to confirm the differential expression of 3 hub genes. Briefly, after blood samples were sequenced interrogating 867 differential genes in our internal screening dataset. After screening GEO databases, 551 DEGs obtained from GSE77103. Fourteen common genes were overlapped through DEGs of GEO datasets and internal screening dataset. Among protein-protein interaction network, 10 hub genes with high degree algorithm were screened out and 3 hub genes of them - ADIPOR1, LGALS3, and GZMB - that were thought to be most associated with the emergence of ASD. Then, we developed a network of miRNA-mRNA regulatory interactions by screening miRNAs (such as hsa-miR-20b-5p, hsa-miR-17-5p, and hsa-miR-216b-5p) that were closely associated to 3 hub genes. Additionally, we discovered 18 different immune cell types associated with ASD using the CIBERSORT algorithm, and we discovered that mononuclear macrophages differed considerably between the 2 groups. Overall, 3 hub genes (ADIPOR1, LGALS3, and GZMB) and 15 candidates miRNAs-target 3 genes regulatory pathways representing potentially novel biomarkers of ASD diseases were revealed. These findings could enhance our knowledge of ASD and offer possible therapeutic targets of ASD patients in the future.

Exploring the molecular mechanism of comorbidity of autism spectrum disorder and inflammatory bowel disease by combining multiple data sets.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is difficult to diagnose. Inflammatory bowel disease (IBD) is a common chronic digestive disease. Previous studies have shown a potential correlation between ASD and IBD, but the pathophysiological mechanism remains unclear. The purpose of this research was to examine the biological mechanisms underlying the differentially expressed genes (DEGs) of ASD and IBD using bioinformatics tools. METHODS: Limma software was used to evaluate the DEGs between ASD and IBD. The GSE3365, GSE18123, and GSE150115 microarray data sets were acquired from the Gene Expression Omnibus (GEO) database. We then performed 6 analyses, namely, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation; weighted gene coexpression network analysis; correlation analysis of hub genes with autophagy, ferroptosis and immunity; transcriptional regulation analysis of hub genes; single-cell sequencing analysis; and potential therapeutic drug prediction. RESULTS: A total of 505 DEGs associated with ASD and 616 DEGs associated with IBD were identified, and 7 genes overlapped between these sets. GO and KEGG analyses revealed several pathways enriched in both diseases. A total of 98 common genes related to ASD and IBD were identified by weighted gene coexpression network analysis (WGCNA), and 4 hub genes were obtained by intersection with the 7 intersecting DEGs, which were PDGFC, CA2, GUCY1B3 and SDPR. We also found that 4 hub genes in the two diseases were related to autophagy, ferroptosis or immune factors. In addition, motif-TF annotation analysis showed that cisbp__M0080 was the most relevant motif. We also used the Connectivity Map (CMap) database to identify 4 potential therapeutic agents. CONCLUSION: This research reveals the shared pathogenesis of ASD and IBD. In the future, these common hub genes may provide new targets for further mechanistic research as well as new therapies for patients with ASD and IBD.