Copper Ion-Inspired Dual Controllable Drug Release Hydrogels for Wound Management: Driven by Hydrogen Bonds.

Bacterial infections and inflammation progression yield huge trouble for the management of serious skin wounds and burns. However, some hydrogel dressing exhibit poor wound-healing capabilities. Additionally, little information is given on the molecular theory of hydrogel gelation mechanisms and drug release performance from drug-polymer network in the water environment. Herein, cationic guar gum (CG) is first mixed with dipotassium glycyrrhizinate (DG), and then crosslinked Cu2+ to strengthen the mechanical strength followed by encapsulating mussel adhesive protein (MAP) as composite dressings. Intriguingly, CG-Cu2+ 0.5-DG10 possessed proper rheological properties and mechanical strength predominantly driven by strong CG-H2O-Cu2+ and Cu2+-CG hydrogen bonding interaction. Weak DG-CG hydrogen bonding only controlled DG release in the initial 4 h, while strong hydrogen bonding is the main force regulating the sustained release of Cu2+ within 48 h. The incorporation of MAP further loosened the tight crosslinking of CG-Cu2+ 0.5-DG10. The screened CG-Cu2+ 0.5-DG10/MAP possessed excellent self-healing, injectability, antibacterial, anti-inflammatory, cell proliferation-promotion activities with high biocompatibility. Therefore, CG-Cu2+ 0.5-DG10/MAP hydrogel expedited wound closure on S. aureus-infected full-thickness skin wound model and lowered necrosis progression to the unburned interspaces on a rat burn model. The results highlight the promising translational potential of Cu2+-inspired hydrogels for the management of burns and infected wounds.

A multihole nozzle controls recrystallization of high-moisture extruded maize starches: Effect of cooling die temperature.

Hot extrusion is utilized for starch modification due to its high mechanical input and product output. Amylose recrystallization commences and primarily depends on intermolecular interactions after conventional extrusion. Hence, the design of a new component based on the existed extrusion system was aimed at facilitating molecular aggregation, potentially accelerating starch recrystallization. In this study, a nozzle sheet comprising 89 holes was integrated into the cooling die. The impact of the multihole nozzle on the structure and in vitro digestibility of extruded maize starches after retrogradation was examined at varying cooling die temperatures. The results showed that the nozzle-assembled extrusion system operated effectively without additional mechanical or yield losses. At 50 °C, the crystallinity of nozzle-produced starch was approximately 70 % higher than that of conventionally extruded starch, predominantly owing to the B-type allomorph of the amylose double helix. Recrystallized amylopectin was also found in these nozzle-produced starches, indicating that multihole nozzle-induced uniaxial elongational flow resulted in the rapid starch crystallization. The increased formation of recrystallized amylose led to improved molecular order in starch structures while reducing their digestibility. These findings revealed a new approach to improve starch crystallinity by incorporating a nozzle sheet in the extrusion process.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

Prostaglandin E2 may clinically alleviate dry eye disease by inducing Th17 cell differentiation.

Dry eye (DE) is a multifactorial ocular surface disease characterised by an imbalance in tear homeostasis. The pathogenesis of DE is complex and related to environmental, immunological (e.g., T helper 17 cells) and other factors. However, the DE disease pathogenesis remains unclear, thereby affecting its clinical treatment. This study aimed to explore the mechanism through which prostaglandin E2 (PGE2) affects DE inflammation by regulating Th17. The DE mouse model was established through subcutaneous injection of scopolamine hydrobromide. The tear secretion test and break-up time (BUT) method were used to detect tear secretion and tear film BUT, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of PGE2, interleukin (IL)-17, IL-6 and tumour necrosis factor (TNF-α) in tear fluid and those of PGE2 and IL-17 in the serum. RT-qPCR and western blotting were used to test the mRNA and protein expression levels of IL-17 and retinoid-related orphan receptor-γt (RORγt). PGE2 was highly expressed in the DE mouse model. The mRNA and protein levels of IL-17 and the key Th17 transcription factor RORγt were increased in tissues of the DE mice. Moreover, PGE2 promoted tear secretion, reduced the BUT, increased the IL-17 concentration in tears and increased the Th17 cell proportion in DE, whereas the PGE2 receptor inhibitor AH6809 reversed the effects of PGE2 on tear secretion, BUT, and the Th17 cell proportion in draining lymph node (DLN) cells. Taken together, the study findings indicate that PGE2 could induce DE-related symptoms by promoting Th17 differentiation.

Pressure-dominated steam explosion for modifying textured soy proteins: Structure and in vitro digestion kinetics.

Textured Soy Proteins (TSPs) have been employed as building blocks in various food processes, but their availability remains limited. In this research, influence of Steam Explosion (SE) with pressure ranges (0, 0.5, 1.0, 1.5 MPa) on the structure and in vitro digestibility of TSPs was investigated. The results showed that 0.5 and 1.0 MPa significantly increased the relative content of ß-sheets and decreased the relative content of α-helices and ß-turns. Correlation analysis revealed that the structural changes made the TSP brittle, with lower thermal stability and resistance to digestion. Moreover, SE decreased the degree of hydrolysis of TSPs in the gastric stage, with the lowest degree observed for the TSP at 0.5 MPa. However, in the intestinal phase, 1.0 and 1.5 MPa significantly increased the hydrolysis degree. These findings provide a better understanding of the SE pressure-modulated quality characteristics of TSPs and suggest the processing potential of modified TSPs as functional ingredients.

Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms.

Intervertebral disc degeneration is closely related to abnormal phenotypic changes in disc cells. However, the mechanism by which disc cell phenotypes are maintained remains poorly understood. Here, Hedgehog-responsive cells were found to be specifically localized in the inner annulus fibrosus and cartilaginous endplate of postnatal discs, likely activated by Indian Hedgehog. Global inhibition of Hedgehog signaling using a pharmacological inhibitor or Agc1-CreERT2-mediated deletion of Smo in disc cells of juvenile mice led to spontaneous degenerative changes in annulus fibrosus and cartilaginous endplate accompanied by aberrant disc cell differentiation in adult mice. In contrast, Krt19-CreER-mediated deletion of Smo specifically in nucleus pulposus cells led to healthy discs and normal disc cell phenotypes. Similarly, age-related degeneration of nucleus pulposus was accelerated by genetic inactivation of Hedgehog signaling in all disc cells, but not in nucleus pulposus cells. Furthermore, inactivation of Gli2 in disc cells resulted in partial loss of the vertebral growth plate but otherwise healthy discs, whereas deletion of Gli3 in disc cells largely corrected disc defects caused by Smo ablation in mice. Taken together, our findings not only revealed for the first time a direct role of Hedgehog-Gli3 signaling in maintaining homeostasis and cell phenotypes of annuls fibrosus and cartilaginous endplate, but also identified disc-intrinsic Hedgehog signaling as a novel non-cell-autonomous mechanism to regulate nucleus pulposus cell phenotype and protect mice from age-dependent nucleus pulposus degeneration. Thus, targeting Hedgehog signaling may represent a potential therapeutic strategy for the prevention and treatment of intervertebral disc degeneration.

Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis.

Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA). Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman's correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes' interactions with drugs. Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs. Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.

The implications of lipid mobility, drug-enhancers (surfactants)-skin interaction, and TRPV1 activation on licorice flavonoid permeability.

Licorice flavonoids (LFs) are derived from perennial herb licorice and have been attaining a considerable interest in cosmetic and skin ailment treatments. However, some LFs compounds exhibited poor permeation and retention capability, which restricted their application. In this paper, we systematically investigated and compared the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) with distinct lipophilicity or "heat and cool" characteristics on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds. The enhancing efficacy was evaluated by enhancement ratio (ER)permeation, ERretention, and ERcom, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipid fluidity, SC water loss, and surface structure alterations, thereby resulting in a higher permeation enhancing effects than other enhancers. CaP could completely occupied drug-skin interaction sites in the SC, while POCC only occupied most drug-skin interactions. Moreover, the enhancing efficacy of both POCC and CaP was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility could help them permeate into the SC. For high-permeation LFs, their permeation was inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, the activation of transient receptor potential vanilloid 1 (TRPV1) could enhance LFs permeation by CaP. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of different enhancers in topical or transdermal formulations.

A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions.

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body's tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii.

Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. The signaling lymphocytic activation molecule (SLAMF) family of receptors are expressed on various hematopoietic and non-hematopoietic cells and can regulate both immune cell activation and cytokine production. Altered expression of certain SLAMF receptors contributes to aberrant immune responses in RA. In RA, SLAMF1 is upregulated on T cells and may promote inflammation by participating in immune cell-mediated responses. SLAMF2 and SLAMF4 are involved in regulating monocyte tumor necrosis factor production and promoting inflammation. SLAMF7 activates multiple inflammatory pathways in macrophages to drive inflammatory gene expression. SLAMF8 inhibition can reduce inflammation in RA by blocking ERK/MMPs signaling. Of note, there are differences in SLAMF receptor (SFR) expression between normal and arthritic joint tissues, suggesting a role as potential diagnostic biomarkers. This review summarizes recent advances on the roles of SLAMF receptors 1, 2, 4, 7, and 8 in RA pathogenesis. However, further research is needed to elucidate the mechanisms of SLAMF regulation of immune cells in RA. Understanding interactions between SLAMF receptors and immune cells will help identify selective strategies for targeting SLAMF signaling without compromising normal immunity. Overall, the SLAMF gene family holds promise as a target for precision medicine in RA, but additional investigation of the underlying immunological mechanisms is needed. Targeting SLAMF receptors presents opportunities for new diagnostic and therapeutic approaches to dampen damaging immune-mediated inflammation in RA.

Concentration-Regulated Fibrillation of Soy Protein: Structure and In Vitro Digestion.

The impact of protein types, heating temperatures, and times on protein fibrillation has been widely studied. However, there is little understanding of the influence of protein concentration (PC) on the protein fibril assembly. In this work, the structure and in vitro digestibility of soy protein amyloid fibrils (SAFs) were investigated at pH 2.0 and different PCs. Significant increases in fibril conversion rate and parallel ß-sheets proportion were observed in SAFs upon increasing the PC from 2 to 8% (w/v). The AFM images showed that curly fibrils were prone to form at 2-6% PCs, while rigid, straight fibrils developed at higher PCs (≥8%). As evidenced in XRD results, increasing PC led to a more stable structure of SAFs with enhanced thermal stability and lower digestibility. Moreover, positive correlations among PC, ß-sheet content, persistence length, enthalpy, and total hydrolysis were established. These findings would provide valuable insights into concentration-regulated protein fibrillation.

Temporal and spatial variation of microplastics in Baotou section of Yellow River, China.

Freshwater rivers play the key role in providing drinking water sources and building the bridge of oceans and lands. Hence, environmental pollutants can be transferred into drinking water through a water treatment process and transported land-based microplastics into the ocean. Microplastics are considered a new pollutant that is becoming a threat to freshwater ecosystems. The present study investigated the temporal and spatial variation of microplastics abundance and their characteristics of occurrence in surface water, sediment and soil samples of Baotou section of Yellow River in China in March 2021 and September 2021. According to the LDIR analysis, the average abundances of microplastics in wet season (surface water 2510.83 ± 2971.27n/L, sediment 6166.67 ± 2914.56n/kg) were higher than that in dry season（surface water 432.5 ± 240.54n/L, sediment 3766.67 ± 1625.63n/kg), particularly being significant difference in the dry and wet seasons of surface water. The predominant polymer types in surface water (PBS and PET during the dry season, PP during the wet season) demonstrated that the temporal variation of microplastics abundance in surface water could be attributed to the combined effect of the regional precipitation, fishing activities and improper disposal of plastic waste. And the results of spatial abundances of microplastics showed that the microplastics abundance of soil and sediment was higher than that in river water and microplastics abundance in the river of the south side was the higher than other water sampling sites, revealing the differences of microplastics burden at the different sampling sites. Moreover, it is worth noting that a large amount of PAM was detected in sediments and soil, but not in water, and the biodegradable plastics PBS and PLA were also detected in the Yellow River. It was a very useful information for evaluating environmental impacts and ecological effects of degradable plastics compared to the traditional plastics after the implementation of a new environmental policy in the future. Thus, this study provided insights into the temporal-spatial characteristics of microplastics in an urban river and raised environmental management awareness of the long-term threat to drinking water safety by microplastics.

Role of the granzyme family in rheumatoid arthritis: Current Insights and future perspectives.

Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by chronic inflammation that affects synovial tissues of multiple joints. Granzymes (Gzms) are serine proteases that are released into the immune synapse between cytotoxic lymphocytes and target cells. They enter target cells with the help of perforin to induce programmed cell death in inflammatory and tumor cells. Gzms may have a connection with RA. First, increased levels of Gzms have been found in the serum (GzmB), plasma (GzmA, GzmB), synovial fluid (GzmB, GzmM), and synovial tissue (GzmK) of patients with RA. Moreover, Gzms may contribute to inflammation by degrading the extracellular matrix and promoting cytokine release. They are thought to be involved in RA pathogenesis and have the potential to be used as biomarkers for RA diagnosis, although their exact role is yet to be fully elucidated. The purpose of this review was to summarize the current knowledge regarding the possible role of the granzyme family in RA, with the aim of providing a reference for future research on the mechanisms of RA and the development of new therapies.

Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly disabling chronic autoimmune disease. Multiple factors contribute to the complex pathological process of RA, in which an abnormal autoimmune response, high survival of inflammatory cells, and excessive release of inflammatory factors lead to a severe chronic inflammatory response. Clinical management of RA remains limited; therefore, exploring and discovering new mechanisms of action could enhance clinical benefits for patients with RA. Important bidirectional communication occurs between the brain and immune system in inflammatory diseases such as RA, and circulating immune complexes can cause neuroinflammatory responses in the brain. The gamma-aminobutyric acid (GABA)ergic system is a part of the nervous system that primarily comprises GABA, GABA-related receptors, and GABA transporter (GAT) systems. GABA is an inhibitory neurotransmitter that binds to GABA receptors in the presence of GATs to exert a variety of pathophysiological regulatory effects, with its predominant role being neural signaling. Nonetheless, the GABAergic system may also have immunomodulatory effects. GABA/GABA-A receptors may inhibit the progression of inflammation in RA and GATs may promote inflammation. GABA-B receptors may also act as susceptibility genes for RA, regulating the inflammatory response of RA via immune cells. Furthermore, the GABAergic system may modulate the abnormal pain response in RA patients. We also summarized the latest clinical applications of the GABAergic system and provided an outlook on its clinical application in RA. However, direct studies on the GABAergic system and RA are still lacking; therefore, we hope to provide potential therapeutic options and a theoretical basis for RA treatment by summarizing any potential associations.

Effect of Acupuncture on Postoperative Pain in Patients after Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

Objective: To evaluate the efficacy and safety of acupuncture compared to that of parecoxib sodium on postoperative pain (POP), postoperative nausea and vomiting (PONV), and the Bruggemann Comfort Scale (BCS) in patients following laparoscopic cholecystectomy (LC). Methods: Eligible patients admitted to the hospital for LC were randomly allocated to either acupuncture or control groups in a 1 : 1 ratio. The subjects in the acupuncture group received acupuncture while those in the control group were injected by parecoxib sodium at their requests. The pain score, PONV score, and BCS were assessed at 0 h, 6 h, 9 h, and 12 h after operation. The primary outcome was the pain score. The secondary outcomes included the number of patients asking for parecoxib sodium from the two groups at 0-6 h and 6-12 h, PONV score, and BCS score. Results: The pain score of the acupuncture group were lower in acupuncture than that in the control group at 6 h and 9 h after operation (P=0.002, P=0.008). However, no difference was found at 12 h. Besides, the number of patients administered parecoxib sodium in acupuncture group was less than that in the control group both at 0-6 h and 6-12 h after operation (P=0.019, P < 0.001). Similarly, there were significantly lower levels of PONV score and higher levels of BCS at 6 h after operation in the acupuncture group than in the control group. However, no difference was found at 9 h and 12 h. Conclusion: Acupuncture can clinically improve the short-term treatment of postoperative pain after LC and reduce the request for extra analgesics; therefore, acupuncture might be a potential method as one of multimodal analgesia techniques to treat POP following LC. Trial Registrations. This trial is registered with ChiCTR2000036885 (Chinese Clinical Trial Registry).

Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis.

Objectives: HTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples. Methods: We enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about 218 bp from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around HTR2A cg15692052 from patients were analyzed by targeted methylation sequencing. Results: We measured methylation status for 7 CpGs in the promoter region of HTR2A and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10-5). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, P=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (FDR=0.02 and 2.81 x 10-6) is signficantly increased while TTTTTCC (FDR =0.01) and TTTTTTT(FDR =6.92 x 10-3) are significantly decreased in RA. We find methylation haplotypes combining with RF and CCP could signficantly enhance the performance of the diagnosing RA and its comorbidities (hypertension, interstitial lung disease, and osteoporosis), especially in interstitial lung disease. Conclusions: In our study, we found signficant hypermethylation of promoter region of HTR2A which indicates the potential clinical diagnostic role in rheumatoid arthritis.

Entrepreneurship education of college students and entrepreneurial psychology of new entrepreneurs under causal attribution theory.

With the rapid development of information technology, the society's demand for innovative talents has become increasingly prominent. The purpose of this study is to optimize the teaching strategies of entrepreneurship education for college students, further cultivate college students' entrepreneurial ideas, and promote the formation of entrepreneurial values. The problems existing in entrepreneurship education in colleges and universities are studied based on entrepreneurial psychology and attribution theory. A questionnaire survey is conducted on the problems with a high probability of entrepreneurial failure of college students. The heads of new ventures in Xi'an are selected. Then, 300 questionnaires are distributed, and 209 are returned. The survey results are analyzed using failure attribution and failure learning. Suggestions are provided for management strategies of new ventures. The results show that the Corrected Item-Total Correlation (CITC) value of R-1 is 0.65, and the CITC value of R-2 is 0.35. In addition, the Kaiser-Meyer-Olkin (KMO) values of entrepreneurial failure attribution and entrepreneurial failure mode are both greater than 0.7, which indicates that the scale of entrepreneurial failure attribution has good validity and can be used for factor analysis. However, the KMO values of entrepreneurial failure attribution and entrepreneurial failure learning model are both greater than 0.7, and the significance of Bartlett sphericity test is 0.00, which indicates that the survey has good validity. The research has practical application and reference value for the cultivation of college students' innovative and entrepreneurial ability.

Biofilm-based delivery approaches and specific enrichment strategies of probiotics in the human gut.

The use of probiotics has been one of the effective strategies to restructure perturbed human gut microbiota following a disease or metabolic disorder. One of the biggest challenges associated with the use of probiotic-based gut modulation strategies is to keep the probiotic cells viable and stable during the gastrointestinal transit. Biofilm-based probiotics delivery approaches have emerged as fascinating modes of probiotic delivery in which probiotics show significantly greater tolerance and biotherapeutic potential, and interestingly probiotic biofilms can be developed on food-grade surfaces too, which is ideal for the growth and proliferation of bacterial cells for incorporation into food matrices. In addition, biofilms can be further encapsulated with food-grade materials or with bacterial self-produced biofilms. This review presents a newly emerging and unprecedently discussed techniques for the safe delivery of probiotics based on biofilms and further discusses newly emerging prebiotic materials which target specific gut microbiota groups for growth and proliferation.

Efficacy and Safety of Amniotic Membrane Transplantation Combined with Closure of Tenon Capsule and Bulbar Conjunctival Space in the Treatment of Primary Pterygium.

Objective: The aim of the study is to evaluate the safety and effectiveness of amniotic membrane transplantation combined with the closure of the tenon capsule and bulbar conjunctival space. Methods: This study retrospectively included 100 patients with primary pterygium who received closed bulbar conjunctiva and tenon capsule space combined with amniotic membrane transplantation in our hospital from January 2020 to June 2021 as the experimental group and 100 patients with routine treatment in the same period as the control group. The postoperative efficacy evaluation and postoperative complications of the two groups were compared, so as to comprehensively evaluate the safety and effectiveness of this method. Results: The results showed that the postoperative complications of the two groups were significantly improved by Fisher's exact test (χ 2 = 14.510, P = 0.006 < 0.05). The comparison results showed that the treatment group showed significant advantages in six indexes compared with the observation group and the difference between the two groups was statistically significant (P < 0.05) of in the NRS score, Prabhasawat score, inspection of the ocular surface comprehensive analyzer, corneal fluorescein staining, conjunctival fluorescein staining in the operation area, breakup time of tear film examination of the two groups at 3, 7 and 14 days, and 1, 6 and 12 months after the operation. Conclusions: Amniotic membrane transplantation combined with the closure of the tenon capsule and bulbar conjunctival space is safer than conventional surgery in the treatment of primary pterygium. It has a shorter recovery time, higher safety, and a positive curative effect. It can be considered to popularize this operation in clinic.

A Novel Necroptosis-Related lncRNA Signature for Osteosarcoma.

Backgrounds: Osteosarcoma (OS) is easy to metastasis. Necroptosis-related long noncoding RNA (lncRNA) (NRlncRNA) plays a vital role in the tumorigenesis of many malignant tumors. Nonetheless, there have been few studies investigating the relations between NRlncRNA and OS. During the investigation, NRlncRNAs in OS were confirmed and characterized and their relationships with prognoses were investigated. Methods: NRlncRNAs were downloaded from The Cancer Genome Atlas (TCGA) OS expression data and clinical-pathological information. First, univariate Cox regression and LASSO regression analyses were used to screen for prognostic-related NRlncRNAs. Second, multivariate regression analyses were used to establish a prognostic nomogram for predicting individual survival probability. Survival analyses demonstrated that high-risk patients (HRPs) had a poor prognosis. In addition, gene set enrichment analyses (GSEA) were used to identify gene function in high- and low-risk groups based on the survival mode. Results: The 7 NRlncRNAs (AC004812.2, AC022915.1, AC073073.2, AC090559.1, AL512330.1, DDN-AS1, and SENCR) were shown to have a distinct difference and were used to construct an NRlncRNA signature. Using the signature as a risk score was an independent factor for OS patients. The signature divided OS patients into the high- and low-risk groups. Furthermore, the seven lncRNAs were significantly enriched in cell migration and metabolism. Conclusions: The 7 NRlncRNA survival models have the potential to serve as therapeutic targets and molecular biomarkers for patients with OS, as well as to precisely predict OS prognoses.