Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.

Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA.

OralExplorer: a web server for exploring the mechanisms of oral inflammatory diseases.

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).

Comprehensive analysis of KLF family reveals KLF6 as a promising prognostic and immune biomarker in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors worldwide, with extremely aggressive and complicated biology. Krüppel-like factors (KLFs) encode a series of transcriptional regulatory proteins and play crucial roles in a variety of processes, including tumor cell differentiation and proliferation. However, the potential biological functions and possible pathways of KLFs in the progression of PDAC remain elusive. METHODS: We systematically evaluated the transcriptional variations and expression patterns of KLFs in pancreatic cancer from the UCSC Xena. Based on difference analysis, the non-negative matrix factorization (NMF) algorithm was utilized to identify the immune characteristics and clinical significance of two different subtypes. The multivariate Cox regression was used to construct the risk model and then explore the differences in tumor immune microenvironment (TIME) and drug sensitivity between high and low groups. Through single-cell RNA sequencing (scRNA-seq) analysis, we screened KLF6 and further investigated its biological functions in pancreatic cancer and pan-cancer. RESULTS: The KLFs exhibited differential expression and mutations in the transcriptomic profile of PDAC. According to the expression of KLFs, patients were classified into two distinct subtypes, each exhibiting significant differences in prognosis and TIME. Moreover, the KLF signature was developed using univariate Cox and Lasso regression, which proved to be a reliable and effective prognostic model. Furthermore, the KLF_Score was closely associated with immune infiltration, response to immunotherapy, and drug sensitivity and we screened small molecule compounds targeting prognostic genes separately. Through scRNA-seq analysis, KLF6 was selected to further demonstrate its role in the malignance of PC in vitro. Finally, pan-cancer analysis emphasized the biological significance of KLF6 in multiple types of tumors and its clinical utility in assessing cancer prognosis. CONCLUSION: This study elucidated the pivotal role of KLF family genes in the malignant development of PC through comprehensive analysis and revealed that KLF6 would be a novel diagnostic biomolecule marker and potential therapeutic target for PDAC.

Sirtuin 1 in osteoarthritis: Perspectives on regulating glucose metabolism.

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments，alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.

Response of occurrence in microplastics and its adsorped cadmium capacity to simulated agricultural environmental scenarios in sludge-amended soil.

Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 µg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems.

Meta-analysis of the effects of CPAP therapy on estimated glomerular filtration rate in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease and may lead to a loss of kidney function. However, it remains unclear whether or not continuous positive airway pressure (CPAP) treatment improves the estimated glomerular filtration rate (eGFR) in patients with OSA. This meta-analysis was designed to investigate the effect of CPAP therapy on eGFR in patients with OSA. METHODS: We searched the electronic databases Web of Science, Cochrane Library, PubMed, and Embase through June 1, 2022. Information about patients, CPAP duration, gender distribution, pre- and post-CPAP treatment eGFR, and age of patients were collected for further analysis. We applied the standardized mean difference (SMD) with a 95%confidence interval (CI) to analyze the pooled effects. Both Stata 12.0 software and Review Manager 5.2 software were employed for all statistical analyses. RESULTS: A sample of 13 studies with 519 patients was included in the meta-analysis. There was no significant change of eGFR levels before and after CPAP usage for patients with OSA (SMD = - 0.05, 95%CI: - 0.30 to 0.19, Z = 0.43, p = 0.67). However, subgroup analysis revealed that the level of eGFR was obviously decreased after CPAP therapy in patients with OSA and CPAP use duration > 6 months (SMD = - 0.30, 95% CI = - 0.49 to - 0.12, z = 3.20, p = 0.001), and elderly patients (> 60 years) (SMD = - 0.32, 95% CI = - 0.52 to - 0.11, z = 3.02, p = 0.002). CONCLUSIONS: Meta-analysis confirmed that OSA treatment with CPAP has no clinically significant effect on eGFR.

Study on Purification, Identification and Antioxidant of Flavonoids Extracted from Perilla leaves.

The flavonoids from Perilla leaves were extracted using flash extraction assisted by ultrasonic extraction with ethanol. Subsequently, macroporous resin was employed for the isolation and purification of these flavonoids, followed by an investigation into their antioxidant activity. The process conditions for the extraction of flavonoids from Perilla leaves were designed and optimized using a one-way experiment combined with a response surface methodology. The optimal extraction conditions were determined as follows: the liquid-solid ratio was 20:1, ethanol volume fraction of 60%, ultrasound temperature of 60 °C, ultrasound time of 10 min and flash evaporation time of 60 s. The optimal extraction rate of flavonoids is 9.8 mg/g. In terms of separation and purification, a high-performance macroporous resin (HPD450 resin) with high purification efficiency was selected through static analysis and adsorption experiments. The optimal enrichment conditions were as follows: loading concentration of 0.06 mg/mL, optimal loading concentration of 20 mL, elution concentration of 70% and 76 mL, providing a reference for the further development and utilization of Perilla leaf flavonoids.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation.

OBJECTIVES: Improper orthodontic force often causes root resorption or destructive bone resorption. There is evidence that T helper 17 (Th17) cells and regulatory T (Treg) cells may be actively involved in bone remodeling during tooth movement. In a combination of in vitro and in vivo studies, we investigated the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under different orthodontic forces and corticotomy. MATERIAL AND METHODS: hPDLCs were cultured in vitro and subjected to different mechanical forces. The expression of interleukin (IL)-6 and transforming growth factor (TGF)-ß in the supernatant and the mRNA levels of hypoxia inducible factor (HIF)-1α, Notch1, and TGF-ß in hPDLCs were investigated. Supernatants were collected and co-cultured with activated CD4+T cells, and the differentiation of Th17/Treg cells was analyzed by flow cytometry. We also established an animal model of tooth movement with or without corticotomy. The tooth movement distance, alveolar bone height, and root resorption were analyzed using micro-computed tomography. Expression of interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, HIF-1α, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and gingiva were investigated. RESULTS: Heavy force repressed cell viability and increased the mortality rate of hPDLCs; it also improved the expression of IL-6, declined the expression of TGF-ß, and promoted the mRNA expression level of HIF-1α. The expression of TGF-ß and Notch1 mRNA decreased and then increased. The supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. The heavy force caused root resorption and decreased alveolar bone height and increased the positive area of IL-17A immunohistochemical staining and the expression of IL-17A, IL-6, HIF-1α, and Notch1 mRNA. Corticotomy accelerated tooth movement, increased the proportion of Foxp3-positive cells, and up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. CONCLUSIONS: During orthodontic tooth movement, the heavy force causes root resorption and inflammatory bone destruction, which could be associated with increased expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement without causing root resorption and periodontal bone loss, which may be related to the increased expression of Treg cells. CLINICAL RELEVANCE: Altogether, this report provides a new perspective on the prevention of inflammatory injury via the regulation of Th17/Treg cells in orthodontics.

Influence of sludge treatment methods on behaviors of microplastics adsorbed cadmium and its driving factors.

The complicated contamination of microplastics (MPs) and heavy metals in sludge has garnered substantial attention in recent years; however, research on the behavior of MPs loading of heavy metals in sludge after sludge treatment methods is limited. Four representative sludge treatment methods were selected herein: anaerobic digestion, thermal drying, thermal hydrolysis (TH), and aerobic composting. Before and after sludge treatment, the chemical bonding of MPs, cadmium (Cd) adsorption properties, and metabolic changes in the microbial community succession was analyzed, and the factors influencing differences in Cd sorption by sludge MPs were explored. The results revealed that Cd adsorption by MPs occurs as multilayer physical adsorption that can be well fitted by Freundlich isotherms. Compared with the other three treatments, TH led to the most significant effect on the chemical bonding properties of the MPs, with a more than two-fold increase in C-O single bonds and CO double bonds, as well as adsorption of the highest amount of Cd at 767 µg/g. In addition, sludge conductivity and water content also affected Cd sorption capacity, with correlation coefficients of 0.405 and -0.384. Pedobacter, Flavobacterium, Lysobacter, and Sphingobacterium in the sludge presented a high degree of coupling with adsorption capacity, it was inferred that the above dominant species of bacteria may affect the adsorption of Cd by microplastics through the production of extracellular enzyme forms.

Simulation of average monthly ozone exposure concentrations in China: A temporal and spatial estimation method.

BACKGROUND: Ozone has adverse effects on human health, it is necessary to obtain the refined ozone exposure concentration. At present, most of existing ozone exposure research is based on ground air quality monitoring station (MS) which gather urban area information only. It is diffcult to estimate the ozone in the areas where MSs are scarce. OBJECTIVE: By combining accurate but uneven data of outdoor ozone exposure concentrations based on MSs and unbiased coverage data based on RS in China, we can improve the accuracy of simulation of average monthly ozone exposure concentrations in monitor-free area. Since ozone concentrations are usually low at night, ozone exposure is assessed during the day (e.g., 10:00-18:00). METHODS: We proposed a space-time geostatistical kriging interpolation based on the composite space/time mean trend model (CSTM) to predict ozone exposure in mainland China, having obtained a refined ozone exposure concentration interpolation map from an MS. We verified the accuracy of the interpolation results and remote sensing (RS) data, while simultaneously determining the distance threshold (according to the data accuracy) to improve the accuracy of the hybrid map. RESULTS: We used a refined smoothing filter to reduce the influence of spatial and seasonal trends on ozone concentration. We found a cutoff separation distance of 175 km at which the two data showed an equal estimation accuracy, and the estimation result was fused with RS data through the distance threshold. Finally, The multi-source data with the best accuracy were fused to obtain the refined map. In China, ozone exposure concentration mainly gathers in the northern and eastern regions as well as part of the central mainland. CONCLUSIONS: RS data can be used to characterize ground ozone exposure concentrations when 24th-layer data and MS data for monitoring ozone exposure concentrations are combined to estimate temporal and spatial ozone exposure in China. Ozone exposure in China can be explored further to provide suggestions for human health and regional economic development.

Dahuang Zhechong pill attenuates CCl4-induced rat liver fibrosis via the PI3K-Akt signaling pathway.

It is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor ß1 and tumor necrosis factor-α in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.

Circular RNA HIPK3 contributes to hyperglycemia and insulin homeostasis by sponging miR-192-5p and upregulating transcription factor forkhead box O1.

It has been shown that circular RNAs, a class of non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of circular RNA HIPK3 (circHIPK3) in diabetes-associated metabolic disorders, including hyperglycemia and insulin resistance. Results show that oleate stimulated circHIPK3 increase, and that circHIPK3 enhanced the stimulatory effect of oleate on adipose deposition, triglyceride (TG) content, and cellular glucose content in HepG2 cells. MiR-192-5p was the potential target of circHIPK3, since circHIPK3 significantly decreased miR-192-5p mRNA level, whereas anti-circHIPK3 significantly increased miR-192-5p mRNA level. Further study shows that transcription factor forkhead box O1 (FOXO1) was a downstream regulator of miR-192-5p, since miR-192-5p significantly decreased FOXO1 expression, whereas circHIPK3 significantly increased FOXO1 expression. Notably, the inhibitory effect of miR-192-5p was significantly reversed by circHIPK3. In vivo study shows that anti-miR-192-5p significantly increased blood glucose content, which was significantly inhibited by FOXO1 shRNA. MiR-192-5p significantly decreased adipose deposition and TG content in HepG2 cells, which was significantly reversed by the co-treatment with circHIPK3. Forskolin/dexamethasone (FSK/DEX) significantly increased cellular glucose, mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), and this stimulatory effect of FSK/DEX was significantly inhibited by miR-192-5p. In the presence of circHIPK3, however, the inhibitory effect of miR-192-5p was totally lost. In summary, the present study demonstrated that circHIPK3 contributes to hyperglycemia and insulin resistance by sponging miR-192-5p and up-regulating FOXO1.

Berberine, a Traditional Chinese Medicine, Reduces Inflammation in Adipose Tissue, Polarizes M2 Macrophages, and Increases Energy Expenditure in Mice Fed a High-Fat Diet.

BACKGROUND The uncoupling protein 1 (UCP1) gene has a role in mitochondrial energy expenditure in brown adipose tissue. This study aimed to investigate the effects of berberine, a benzylisoquinoline alkaloid used in traditional Chinese medicine, on energy expenditure, expression of the UCP1 gene, the cell stress protein inositol-requiring enzyme 1α (IRE1α), apoptosis genes, and macrophage phenotype (M1 and M2) in white and brown adipose tissue in an obese mouse model fed a high-fat diet. MATERIAL AND METHODS Four-week-old C57BL/6J male mice (n=20) were divided into a high-fat diet group, a normal diet group, a group treated with berberine at 100 mg/kg/d in 0.9% normal saline, and a non-treated group. Whole-body fat mass, blood glucose, insulin resistance, and oxygen expenditure during physical activity were measured. After 16 weeks, the mice were euthanized for examination of liver and adipose tissue. The expression of pro-inflammatory cytokines, apoptosis genes, thermogenic genes (including UCP1), and IRE1α, were investigated using immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), in white and brown adipose tissue. Magnetic cell sorting harvested M1 and M2 macrophages in adipose tissue. Clodronate liposomes were used to inhibit macrophage recruitment. RESULTS Berberine treatment in mice fed a high-fat diet increased energy metabolism, glucose tolerance, and expression of UCP1, and reduced expression of pro-inflammatory cytokines, macrophage recruitment, and resulted in M2 macrophage polarization in white adipose tissue. Polarized M2 macrophages showed reduced expression of apoptotic genes and IRE1α. CONCLUSIONS Berberine improved metabolic function in a mouse model fed a high-fat diet.

Plasmonic behaviors of metallic AZO thin film and AZO nanodisk array.

Aluminum-doped zinc oxide (AZO) is well known as transparent conducting material for electro-optical devices, but is rarely used as plasmonic material, particularly on the localized surface plasmon resonance (LSPR) behavior of AZO nanostructure and its plasmonic devices. In this study, we systematically investigate the plasmonic behaviors of AZO thin films and patterned AZO nanostructures with various structural dimensions under different annealing treatments. We find that AZO film can possess highly-tunable, metal-like, and low-loss plasmonic property and the LSPR characteristic of AZO nanostructure is observed in the near-infrared (NIR) region under proper annealing conditions. Finally, environmental index sensing is performed to demonstrate the capability of AZO nanostructure for optical sensing application. High index sensitivity of 873 nm per refractive index unit (RIU) variation is obtained in experiment.

Graphene oxide as the passivation layer for Cu(x)O photocatalyst on a plasmonic Au film and the corresponding photoluminescence study.

The contribution of graphene oxide (GO) on photocatalytic effects of Cu(x)O on plasmonic Au is investigated. It is found that the H(2) evolution rate from pure water is enhanced 1.4 fold using the visible-active Cu(x)O/GO photocatalyst, as compared with Cu(x)O without GO. In addition, the intensity of photoluminescence of Cu(x)O/GO can be enhanced as much as 2.85 fold as compared with Cu(x)O without GO. The enhancement is due to the negative fixed charge in GO, which can passivate the surface of Cu(x)O and suppress recombination of minority electrons at the surface. The results from optical characterization in this study can help to prove the proposed mechanism of passivation.

Inter-allelic prion propagation reveals conformational relationships among a multitude of [PSI] strains.

Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains--named VH, VK, and VL--were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N-terminal prion-forming segment. The six new strains exhibit complex inter-conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This "large number of variations on a small number of basic themes" may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains.

The Research on Risk Factors for Adolescents' Mental Health.

There is a growing tendency for mental health disorders to emerge during adolescence. These disorders impair emotional, cognitive, and behavioral functioning, such as unsatisfying peer relationships, disruptive behavior, and decreased academic performance. They also contribute to vulnerability in later adulthood which negatively influences life-long well-being. Thus, research into etiology is imperative to provide implications for prevention and intervention within family and school practices. It is suggested that the onset of psychological disorders, such as depression and anxiety, is closely related to stress levels and patterns of stress reaction. Therefore, considerable research has investigated the link between hereditary factors, economic status, dispositional vulnerability, social relationships, and stress levels. The current study examines existing evidence and identifies multifaceted risk factors for adolescents' mental problems across three layers, including individual traits and personality, family status and practices, as well as peer relationships, and school climate. It is also suggested that factors from these three perspectives interact and are closely interconnected, directly or indirectly contributing to adolescent psychopathology. The implications for future development of prevention and intervention programs, as well as therapy, are discussed.

Comparison of in-patient glucose team based management with conventional blood glucose management- a retrospective study from China.

BACKGROUND: Glycemic control for patients with diabetes in the surgical department is often unsatisfactory. Compounding this issue is the fact that conventional glucose management models are often inefficient and difficult to monitor over time. OBJECTIVE: To investigate the impact of inpatient glucose team-based management on glycemic control and hospital days in surgical patients with diabetes. METHODS: A retrospective analysis was conducted on 4156 patients with diabetes in the surgical department who received inpatient management of diabetes at a tertiary medical center from June 2020 to May 2022. Based on whether they received inpatient glucose team-based management, the surgical patients with diabetes were divided into two groups: the inpatient glucose team-based management (GM group, consisting of 1698 participants) and the conventional blood glucose management group (control group, consisting of 2458 participants). We compared the two groups in terms of glycemic control, hospital days, and health-care costs. Multiple logistic regression analysis was performed to build the hospital days prediction model and nomogram. Finally, the performance of the model was evaluated. RESULTS: The rate of glucose detection was higher in the GM group at 2 h postprandial (P < 0.01). The incidence of hypoglycemia and severe hyperglycemia, blood glucose attainment time, pre-operative preparation days, hospital days, and health-care costs were lower in the GM group than in the control group (P < 0.01). The linear regression model revealed that blood glucose attainment time, incidence of hypoglycemia (< 3.9mmol/L), preoperative preparation days, perioperative complications, and health-care costs were the factors influencing the hospital days (Total Point 83.4 points, mean hospital days 9.37 days). Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting hospital days (area under the ROC curve 0.83, 95% confidence interval [CI], 0.74 to 0.92). CONCLUSION: Inpatient glucose team-based management demonstrated significant improvements in glycemic control among surgical patients with diabetes, resulting in reduced hospital days and associated costs. The developed nomogram also exhibited promising potential in predicting hospital days, offering valuable clinical applications.

Supramolecular polymers with dual energy storage mechanism for high-performance supercapacitors.

In this paper, we prepared the supramolecular polymers (MWCNT-APP-s) with a dual energy storage mechanism as the electrode materials by the coordination of four transition metal ions with the small molecule chelator (APP) and functionalized carbon nanotubes, respectively. Among four MWCNT-APP-s, MWCNT-APP-Fe has the characteristics of moderate micropore/mesopore, significant hydrophobicity, redox property and functional groups. Interestingly, the redox reaction of Fe3+/Fe2+ and -CN-/-CN- transformation give MWCNT-APP-Fe an energy storage basis of pseudocapacitance, while MWCNTs and the micro/mesopore structure in MWCNT-APP-Fe provide a double-layer energy storage platform. As expected, on base of the dual energy storage mechanism, the symmetric supercapacitor assembled with MWCNT-APP-Fe has a higher specific capacity (Cs, 421 F g-1 at 1 mV s-1) as well as a long-lasting stability of 94.8% capacity retention with 99% Coulombic efficiency after 10,000 cycles at 20 mV s-1. More notably, the relevant aqueous Zn2+ hybrid supercapacitor provides a high capacity (Cm) of 191 mAh g-1 at 0.5 A g-1 and a long duration of over 2000 cycles at 50 A g-1, with a capacity retention of 92.4%. In summary, MWCNT-APP-Fe with a dual energy storage mechanism enables a potential application as an electrode material for high-performance supercapacitor.