An association study of m6A methylation with major depressive disorder.

OBJECTIVE: To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD). METHODS: Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated. RESULTS: Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed. CONCLUSION: Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

Machine learning-based medical imaging diagnosis in patients with temporomandibular disorders: a diagnostic test accuracy systematic review and meta-analysis.

OBJECTIVES: Temporomandibular disorders (TMDs) are the second most common musculoskeletal condition which are challenging tasks for most clinicians. Recent research used machine learning (ML) algorithms to diagnose TMDs intelligently. This study aimed to systematically evaluate the quality of these studies and assess the diagnostic accuracy of existing models. MATERIALS AND METHODS: Twelve databases (Europe PMC, Embase, etc.) and two registers were searched for published and unpublished studies using ML algorithms on medical images. Two reviewers extracted the characteristics of studies and assessed the methodological quality using the QUADAS-2 tool independently. RESULTS: A total of 28 studies (29 reports) were included: one was at unclear risk of bias and the others were at high risk. Thus the certainty of evidence was quite low. These studies used many types of algorithms including 8 machine learning models (logistic regression, support vector machine, random forest, etc.) and 15 deep learning models (Resnet152, Yolo v5, Inception V3, etc.). The diagnostic accuracy of a few models was relatively satisfactory. The pooled sensitivity and specificity were 0.745 (0.660-0.814) and 0.770 (0.700-0.828) in random forest, 0.765 (0.686-0.829) and 0.766 (0.688-0.830) in XGBoost, and 0.781 (0.704-0.843) and 0.781 (0.704-0.843) in LightGBM. CONCLUSIONS: Most studies had high risks of bias in Patient Selection and Index Test. Some algorithms are relatively satisfactory and might be promising in intelligent diagnosis. Overall, more high-quality studies and more types of algorithms should be conducted in the future. CLINICAL RELEVANCE: We evaluated the diagnostic accuracy of the existing models and provided clinicians with much advice about the selection of algorithms. This study stated the promising orientation of future research, and we believe it will promote the intelligent diagnosis of TMDs.

A superficial esophageal cancer with a diverticulum cured by endoscopic submucosal dissection.

Esophageal diverticulum are rare. However, Esophageal cancer that involves diverticula is relatively rare. Here we reported a rare case of a superficial esophageal cancer with an esophageal diverticulum, which was invisible before the endoscopic submucosal dissection. The cancer was successfully removed by ESD with no perforation.

Application of Platelet-Rich Fibrin Derivatives for Mandibular Third Molar Extraction Related Post-Operative Sequelae: A Systematic Review and Network Meta-Analysis.

PURPOSE: Leukocyte- and platelet-rich fibrin (L-PRF) and advanced-platelet-rich fibrin (A-PRF) that are derivatives of PRF (platelet-rich fibrin) accelerate wound healing and reduce postoperative sequelae after tooth extraction. This network meta-analysis aimed to investigate the effectiveness of L-PRF and A-PRF in mandibular third molar extraction and provide suggestions for alleviating postoperative symptoms and signs. METHODS: A comprehensive search of the literature was conducted in PubMed, Embase, Web of Science, and SinoMed databases up to Oct 9, 2020. Three types of randomized controlled trials were included to investigate the effects of PRF derivatives after extracting mandibular third molars: A-PRF and L-PRF groups; A-PRF and control groups; L-PRF and control groups. Their relative effectiveness and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) with STATA 16.0 and Revman 5.3, respectively. RESULTS: Ten randomized controlled trials were included, with 307 mandibular third molar extraction patients involved. The results showed that A-PRF had the best effect among the 3 groups in improving postoperative pain on the third (SUCRA = 98.2%) and seventh (SUCRA = 88.4%) days; L-PRF promoted soft tissue healing (MD = -0.90, 95% CI [-1.40, -0.40], P = .0004) on the seventh day compared with the control. However, other comparisons showed no significant differences (P > .05). CONCLUSION: The limited results confirmed that PRF derivatives only reduced some postoperative symptoms and did not prevent them all. Application of A-PRF after third molar extraction reduced postoperative pain, and L-PRF improved the degree of soft tissue healing.

Dredging mitigates cyanobacterial bloom in eutrophic Lake Nanhu: Shifts in associations between the bacterioplankton community and sediment biogeochemistry.

Cyanobacterial blooms are a worldwide environmental problem, which is partly attributed to their access to excessive nitrogen (N) and phosphorus (P). Preventing the blooms by reducing N and P from internal inputs is viewed as a challenge. To evaluate the effects of dredging on cyanobacterial abundances and bacterioplankton communities, water and sediment samples were collected from eutrophic Lake Nanhu (Wuhan, China) before dredging (2017) and after dredging (2018). After dredging, significant decreases were observed for sediment nutrients (e.g., C, N, and P sources); C-, N-, P-, and S-cycling-related enzyme activity; N- and P-cycling-related gene abundance; microbial abundance; and dramatic changes were observed in the composition of the sediment microbial community. The release rates of nutrient including nitrogen, phosphorus, and organic matter decreased after dredging, and sediment biogeochemistry was closely correlated to nutrient release rates. Additionally, our observations and analyses indicated that the abundance and diversity of the bacterioplankton community decreased significantly, the composition and interaction of the bacterioplankton community dramatically changed, and the bacterioplankton community function (e.g., N, P-cycling-related enzymes and proteins) down regulated after dredging. Water and sediment physicochemical factors explained 72.28% variation in bacterioplankton community composition, and these physicochemical factors were significantly correlated with diversity, composition, and function of bacterioplankton community. Our findings emphasized that cyanobacterial blooms in freshwater ecosystems were closely correlated with noncyanobacterial bacterioplankton that were largely conserved at the phylum level, with Proteobacteria, Actinobacteria, and Bacteroidetes as the main taxa. To our knowledge, this is the first report clarifying the mechanism of cyanobacterial blooms mitigation by dredging, via changing the association between the bacterioplankton community and sediment biogeochemistry. Our findings are of significance and indicate that dredging is effective for mitigating cyanobacterial blooms.

Resilience evaluation for UAV swarm performing joint reconnaissance mission.

The resilience of unmanned aerial vehicle (UAV) swarm is its joint capability to resist possible threat, adapt to disruptive events, and restore its intended performance under a specific time period. The quantitative assessment of the UAV swarm resilience requires a thorough understanding of its missions. In this paper, a mission-oriented framework is proposed to implement the resilience evaluation for the UAV swarm. Guided by the framework, the resilience evaluation for the UAV swarm performing joint reconnaissance mission is studied. A UAV swarm model is developed for joint reconnaissance mission based on complex networks and agent-based models. The following aspects of the UAV swarm are considered in the proposed model, namely, the mission orientation, UAV attributes, swarm topology, UAV cooperative strategy, UAV information exchange and fusion strategy, potential threats, recovery strategies, etc. Then, a novel performance metric is proposed to measure the mission capability of the UAV swarm performing joint reconnaissance mission. Results from the simulations show that, compared with existing studies, the proposed approach can provide more realistic and objective resilience evaluation for the mission-oriented UAV swarm. The above works can be used to support the decision making and the optimal design of the UAV swarm, given different missions.

Phenotypic switching of vascular smooth muscle cells in the 'normal region' of aorta from atherosclerosis patients is regulated by miR-145.

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to an adverse proliferative phenotype is a hallmark of atherosclerosis or vascular restenosis. However, the genetic modulators responsible for this switch have not been fully elucidated in humans nor have they been correlated with clinical abnormalities. This study investigated genetic mechanisms involved in phenotypic switching of VSMCs at non-defect areas of the aorta in patients with atherosclerosis. Aortic wall samples were obtained from patients with (N = 53) and without (N = 27) atherosclerosis undergoing cardiovascular surgery. Vascular smooth muscle cell cultures were generated, and expression of microRNA-145 (miR-145), its target gene Kruppel-Like Factor 5 (KLF5) and Myocardin (MYOCD, a smooth muscle-specific transcriptional coactivator) were analysed using RT-qPCR, along with expression of relevant proteins. Vascular smooth muscle cells were transduced with miR-145 inhibitor and mimic to determine the effect of miR-145 expression on VSMC proliferation. miR-145 expression decreased while KLF5 expression increased in atherosclerotic aortas. Atherosclerotic samples and VSMCs had decreased expression of contractile markers calponin and alpha smooth muscle actin (α-SMA) and MYOCD. miR-145 inhibitor-transduced VSMCs from non-atherosclerotic patients showed decreased expression of calponin and α-SMA and increased proliferation compared with non-transduced controls, and these levels were close to those of atherosclerotic patients. miR-145 mimic-transduced VSMCs from atherosclerotic patients showed increased expression of calponin and α-SMA and decreased proliferation compared with non-transduced controls, and these levels were close to those found in non-atherosclerotic patients. These data demonstrate that miR-145 modulates the phenotypic switch of VSMCs from a contractile to a proliferative state via KLF5 and MYOCD in atherosclerosis.

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.

The tumor suppressor p53 is one of the most frequently mutated genes in hepatocellular carcinoma (HCC). Previous studies demonstrated that CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in tumor cells. However, the research on the application of CP-31398 to liver cancer has not been reported. Here, we investigated the effects of CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In tumor xenografts developed by PLC/PRF/5 cells, the inhibition of tumor growth by CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that CP-31398 inhibited the growth of p53-mutated liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that CP-31398 blocked the growth of xenografts tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.

In Situ Electrochemical Synthesis and Deposition of Discotic Hexa-peri-hexabenzocoronene Molecules on Electrodes: Self-Assembled Structure, Redox Properties, and Application for Supercapacitor.

Discotic hexa-peri-hexabenzocoronene (HBC) molecules are synthesized by electrochemical cyclodehydrogenation reaction and in situ self-assembled to π-electronic, discrete nanofibular objects with an average diameter about 70 nm, which are deposited directly onto the electrode. The nanofibers consist of columnar arrays of the π-stacked HBC molecules and the intercolumnar distance is determined to be 1.19 nm by X-ray diffraction, which corresponds well to the distance of 1.1 nm observed by high-resolution transmitting electron microscopy. The diameter of the molecular columns matches the size of the discotic HBC molecule indicating face-to-face π-stacking of HBC units in the column. The HBC nanofibers on electrode are redox active, and the nanosized columnar structures provide a huge surface area, which is a great benefit for the charging/discharging process, delivering excellent capacitance of 155 F g(-1) . The described electrochemical deposition method shows great advantage for self-assembling the family of insoluble and structurally designable graphene-like nano materials, which constitutes an important step toward molecular electronics.

CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.

Profiles of Circulating Exosomal Mirna in Patients with SAPHO Patients by High-Throughput Sequencing.

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease that is characterized by autoinflammatory lesions on both bones and skin. The diverse manifestations and limited understanding of its etiology have hindered the diagnosis and treatment of this condition. SAPHO syndrome is also classified as a primary inflammatory osteitis. The onset of osteoarticular involvement in this disease is typically gradual, and the identification of associated biomarkers may be crucial for accurate diagnosis, effective treatment, and a better understanding of its underlying mechanisms. METHODS: We enrolled a total of 6 SAPHO patients and 3 healthy volunteers for this study. The miRNA expression profile in circulating exosomes was analyzed using next-generation sequencing. A total of 45 miRNAs were found to be differentially expressed in SAPHO patients. Linear discriminant analysis effect size analysis and Wilcoxon rank-sum test were employed to identify biomarkers based on these differentially expressed miRNAs. Among them, we selected 4 miRNAs as biomarkers for SAPHO syndrome, resulting in an area under the receiver operating characteristic curve of 1. RESULTS: The differentially expressed miRNAs indicated enrichment in immune system and endocrine system-related KEGG pathways, as well as infectious diseases and cancers. Furthermore, the most significantly enriched molecular functions in GO analysis were protein binding and catalytic activity. CONCLUSION: The exosomal miRNA profile in SAPHO syndrome exhibited significant changes, suggesting its potential as a candidate biomarker for diagnostic assistance, although further investigation is warranted to elucidate their role in the pathology.

Shaoyao Decoction reduced T lymphocyte activation by regulating of intestinal flora and 5-hydroxytryptamine metabolism in ulcerative colitis.

BACKGROUND: Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. METHODS: The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. RESULTS: In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. CONCLUSION: Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.

The gut microbiota intervenes in glucose tolerance and inflammation by regulating the biosynthesis of taurodeoxycholic acid and carnosine.

Objective: This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments. Methods: In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils. Results: Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils. Conclusion: Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt.

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C17H19F3N3O3·C4H5O6·2(H2O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.

Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.

BACKGROUND: In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment. METHODS: An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing. RESULTS: The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend. CONCLUSION: EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.

Lake-centred sedentary lifestyle of early Tibetan Plateau Indigenous populations at high elevation 4,400 years ago.

The onset of sedentism on the Tibetan Plateau is often presumed to be associated with the dispersal of agriculture or farmers from archaeological sites located in the low elevation margins of the plateau. Previous studies of the plateau assumed that all foragers were probably mobile, but few systematic excavations at forager sites have been conducted to inform us about their settlement patterns. Here we report the world's highest elevation sedentary way of living exhibited by the Mabu Co site at 4,446 metres above sea level, deep in the interior of the Tibetan Plateau 4,400-4,000 years ago. Our interdisciplinary study indicates that the site was occupied by Indigenous inhabitants of the plateau, representing the earliest known DNA evidence of foragers who predominantly harbour the southern plateau ancestry. The evidence shows that they had a sedentary lifestyle primarily supported by fishing at nearby lakes, supplemented by mammal and bird hunting, as well as small-scale exchanges of millet and rice crops.

Sexual function assessment in patients with SAPHO syndrome: a cross-sectional study.

INTRODUCTION: SAPHO syndrome is a group of special syndromes characterized by synovitis, acne, pustulosis, hyperostosis and osteitis. Skin lesions and joint damage are the main clinical manifestations. Among them, females mostly present with palm toe pustulosis, while males have severe acne as the main external manifestation. The bone and joint damage characterized by bone hypertrophy and osteitis is the core manifestation of SAPHO and affects all parts of the body. SAPHO syndrome causes great physical and mental suffering to patients, and it also brings a huge financial burden to the family. The purpose of this study is to explore the impact of SAPHO on the quality of sexual life of patients. METHODS: We screened and included 249 SAPHO patients (169 women and 80 men) from Peking Union Medical College Hospital (Beijing, China). First, we recorded the basic situation of the patient through questionnaires (including gender, age, SAPHO duration, BMI, smoking, drinking, marital status, educational level, occupational status and work status.). Then, the patient needed to fill in the Short Form-36 quality of life questionnaire (SF-36 QoL) to record the quality of life. For Sexual dysfunction (SD), female patients needed to fill in the Female Sexual Function Index (FSFI) to assess the quality of sexual life; while the International Index of Erectile Function (IIEF) was used to assess the SD of male patients. At the same time, we used self-esteem and relationship questionnaire (SEAR) to analyze the psychological state of SAPHO patients. Finally, we performed statistical analysis on the data obtained, and then explored the connection between SAPHO and SD. RESULTS: In this cross-sectional study, a total of 249 patients completed the questionnaire and constituted the study population. We found that among 169 female patients, 124 patients had FSD (73.4%); while 45 patients did not have FSD (26.6%); and among 80 male patients, 45 (56.3%) had ED; However, 35 patients did not have ED (43.7%). The results of the quality of life and mental state assessment showed that female patients with SD showed lower scores in terms of mental state. Among all male participants, we found no significant difference in quality of life and mental state among participants with or without SD. In addition, there was no significant difference in the duration of SAPHO between female and male participants with or without SD. CONCLUSION: This study is the first to evaluate the SD of SAPHO patients. The incidence of SD in female SAPHO patients is higher than that in male patients; the cause of female SD may be mainly psychological factors. These results prove that it is particularly important to focus on regulating their psychological state while diagnosing and treating SAPHO patients in clinical practice.

In situ photo-crosslinked hydrogel promotes oral mucosal wound healing through sustained delivery of ginsenoside Rg1.

Oral mucosal wounds exhibit an increased susceptibility to inflammation as a consequence of their direct exposure to a diverse range of microorganisms. This causes pain, slow healing, and other complications that interfere with patients' daily activities like eating and speaking. Consequently, patients experience a significant decline in their overall quality of life. Therefore, the pursuit of novel treatment approaches is of great importance. In this study, ginsenoside Rg1, a natural active substance extracted from ginseng root, was chosen as a therapeutic agent. It was encapsulated in a screened photo-crosslinked hydrogel scaffold for the treatment of mucosal defects in the rat palate. The results demonstrated that Rg1-hydrogel possessed excellent physical and chemical properties, and that oral mucosa wounds treated with Rg1-hydrogel exhibited the greatest healing performance, as evidenced by more pronounced wound re-epithelialization, increased collagen deposition, and decreased inflammatory infiltration. Subsequent investigations in molecular biology confirmed that Rg1-hydrogel stimulated the secretion of repair-related factors and inhibited the secretion of inflammatory factors. This study demonstrated that the hydrogel containing ginsenoside Rg1 significantly promotes oral mucosal tissue healing in vivo. Based on the findings, it can be inferred that the Rg1-hydrogel has promising prospects for the therapeutic management of oral mucosal wounds.

Enhanced removal of Cr(VI) by polyethyleneimine-modified bamboo hydrochar.

Hydrochar is an environmentally friendly and cheap adsorbent, but its adsorption amounts for anions is very limited. The functionalized hydrochar can overcome this shortcoming. Herein, polyethyleneimine-modified hydrochar (PEI-HC) was synthesized from hydrothermal carbonization (HTC) of methyl acrylate and bamboo after addition of initiator ammonium persulfate, and then modified by polyethyleneimine (PEI), which was used to treat Cr(VI). PEI-HC was tested by XANES, EXAFS, SEM-EDS, XPS, FTIR, N2 sorption isotherms, zeta potential, and elemental analyses. The characterizations showed that PEI was successfully grafted onto hydrochar, and the PEI-HC was rich in N and O functional groups, which presented high Cr(VI) sorption ability (528.41 mg·g-1 at pH 2). The bath experiments found the pseudo-second-order kinetic and Freundlich equations can well describe the adsorption kinetics and isotherm of the Cr(VI) adsorption onto PEI-HC, respectively. Electrostatic interaction, reduction, complexation, and H-bonding are the main removal mechanisms as supported by XANES, EXAFS, XPS, and FTIR. This study provides a strategy of combining HTC and free radical graft polymerization to convert agricultural and forestry wastes into functionalized hydrochar, showing highly efficient removal of Cr(VI).

An association study of clock genes with major depressive disorder.

OBJECTIVE: To study the relationship between clock genes and Major Depressive Disorder (MDD). METHODS: GEO database was used to obtain the chip data and clinical information of datasets GSE98793, GSE39653 and GSE52790. The differentially expressed clock genes were found through the analysis of the differentially expressed genes between MDD and healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) enrichment analysis were performed on the differential expressed clock genes. Lasso Regression and Support Vector Machine (SVM) method were used for screening the differential expressed clock genes. Logistic regression was used to establish a diagnostic model for depression with the screened genes. Receiver Operating Characteristic (ROC) Curve was used to verify the model. Gene differential expression analysis was performed for MDD with high scores and MDD with low scores in the diagnostic model. Gene Set Enrichment Analysis (GSEA) enrichment analysis was performed for differentially expressed genes. Single-gene GSEA was used to analyze each gene in the model separately. Cibersort method was used to analyze the immune infiltration of MDD and healthy controls, and the correlation between immune cells and clock genes was analyzed. Cytoscape was used to analyze the clock gene interaction network. The DGIdb website was used to predict potentially effective therapeutic drugs for clock genes closely related to MDD. RESULTS: Six genes were identified by differential expression analysis of clock genes between MDD and healthy controls. GO and KEGG enrichment analysis of 6 genes showed that their pathways were concentrated such as circadian rhythm, rhythmic process, TGF - beta signaling pathway, longevity regulating pathway-multiple species, adipocytokine signaling pathway and so on. Lasso regression and SVM were used to screen out 5 clock genes (HDAC1, ID3, NFIL3, PRKAA1, TNF) for MDD. The diagnostic model of depression was established according to the 5 clock genes. The area under the curve (AUC) of the established depression diagnostic model was 0.686. Gene difference analysis was performed between MDD patients with high score of clock gene diagnostic model and MDD patients with low score. GSEA was performed for the differential genes showed that the most enriched pathways were:adipocytokine signaling pathway, TGF beta signaling pathway, oxidative phosphorylation, primary immunodeficiency, and so on. The single gene GSEA showed that the most enriched pathways were Toll like receptor signaling pathway, glucolipid metabolism, amino acid metabolism, neuroactive ligand receptor interaction, and so on. The results of immune infiltration analysis showed that NK cells resting and Macrophages M2 were different between MDD and control groups. In MDD, the gene closely related to NK cells resting was HDAC1, and the genes closely related to Macrophages M2 were HDAC1 and NFIL3. The RNA interactions network of clock genes shows that the regulation process is complex, which can provide a reference for subsequent related research. Potential therapeutic drugs predict display, among the 5 clock genes, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs. CONCLUSION: Among all CLOCK genes, HDAC1, ID3, NFIL3, PRKAA1, TNF are closely related to MDD. Among them, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs.