Chemical Dynamics of Selenium Nanoparticles in Archaeal Systems.

Methanogenic archaea, characterized by their cell membrane lipid molecules consisting of isoprenoid chains linked to glycerol-1-phosphate via ether bonds, exhibit exceptional adaptability to extreme environments. However, this distinct lipid architecture also complicates the interactions between methanogenic archaea and nanoparticles. This study addresses this challenge by exploring the interaction and transformation of selenium nanoparticles (SeNPs) within archaeal Methanosarcina acetivorans C2A. We demonstrated that the effects of SeNPs are highly concentration-dependent, with chemical stimulation of cellular processes at lower SeNPs concentrations as well as oxidative stress and metabolic disruption at higher concentrations. Notably, we observed the formation of a protein corona on SeNPs, characterized by the selective adsorption of enzymes critical for methylotrophic methanogenesis and those involved in selenium methylation, suggesting potential alterations in protein function and metabolic pathways. Furthermore, the intracellular transformation of SeNPs into both inorganic and organic selenium species highlighted their bioavailability and dynamic transformation within archaea. These findings provide vital insights into the nano-bio interface in archaeal systems, contributing to our understanding of archaeal catalysis and its broader applications.

Iodine-doped carbon nanotubes boosting the adsorption effect and conversion kinetics of lithium-sulfur batteries.

Compared with lithium-ion batteries (LIBs), lithium-sulfur batteries (LSBs), based on electrochemical reactions involving multi-step 16-electron transformations provide higher specific capacity (1672 mAh g-1) and specific energy (2600 Wh kg-1), exhibiting great potential in the field of energy storage. However, the inherent insulation of sulfur, slow electrochemical reaction kinetics and detrimental shuttle-effect of lithium polysulfides (LiPSs) restrict the development of LSBs in practical applications. Herein, the iodine-doped carbon nanotubes (I-CNTs) is firstly reported as sulfur host material to the enhance the adsorption-conversion kinetics of LSBs. Iodine doping can significantly improve the polarity of I-CNTs. Iodine atoms with lone pair electrons (Lewis base) in iodine-doped CNTs can interact with lithium cations (Lewis acidic) in LiPSs, thereby anchoring polysulfides and suppressing subsequent shuttling behavior. Moreover, the charge transfer between iodine species (electron acceptor) and CNTs (electron donor) decreases the gap band and subsequently improves the conductivity of I-CNTs. The enhanced adsorption effect and conductivity are beneficial for accelerating reaction kinetics and enhancing electrocatalytic activity. The in-situ Raman spectroscopy, quasi in-situ electrochemical impedance spectroscopy (EIS) and Li2S potentiostatic deposition current-time (i-t) curves were conducted to verify mechanism of complex sulfur reduction reaction (SRR). Owing to above advantages, the I-CNTs@S composite cathode exhibits an ultrahigh initial capacity of 1326 mAh g-1 as well as outstanding cyclicability and rate performance. Our research results provide inspirations for the design of multifunctional host material for sulfur/carbon composite cathodes in LSBs.

Reliability and validity of the Chinese version of the Information Security Attitude Questionnaire for nurses.

AIM: Nurses play a crucial role within medical institutions, maintaining direct interaction with patient data. Despite this, there is a scarcity of tools for evaluating nurses' perspectives on patient information security. This study aimed to translate the Information Security Attitude Questionnaire into Chinese and validate its reliability and validity among clinical nurses. DESIGN: A cross-sectional design. METHODS: A total of 728 clinical nurses from three hospitals in China participated in this study. The Information Security Attitude Questionnaire (ISA-Q) was translated into Chinese utilizing the Brislin two-way translation method. The reliability was assessed through internal consistency coefficient and test-retest reliability. The validity was determined through the Delphi expert consultation method and factor analysis. RESULTS: The Chinese version of ISA-Q consists of 30 items. Cronbach's α coefficient of the questionnaire was 0.930, and Cronbach's α coefficient of the six dimensions ranged from 0.781 to 0.938. The split-half reliability and test-retest reliability were 0.797 and 0.848, respectively. The content validity index (S-CVI) was 0.962. Exploratory factor analysis revealed a 6-factor structure supported by eigenvalues, total variance interpretation, and scree plots, accounting for a cumulative variance contribution rate of 69.436%. Confirmatory factor analysis further validated the 6-factor structure, demonstrating an appropriate model fit. CONCLUSION: The robust reliability and validity exhibited by the Chinese version of ISA-Q establish it as a dependable tool for evaluating the information security attitudes of clinical nurses. IMPLICATIONS FOR NURSING PRACTICE: The Chinese iteration of the ISA-Q questionnaire offers a profound insight into the information security attitudes held by clinical nurses. This understanding serves as a foundation for nursing managers to develop targeted intervention strategies aimed at fortifying nurses' information security attitudes, thereby enhancing patient safety.

Algorithm for community security risk assessment and influencing factors analysis by back propagation neural network.

This paper aims to accurately assess and effectively manage various security risks in the community and overcome the challenges faced by traditional models in handling large amounts of features and high-dimensional data. Hence, this paper utilizes the back propagation neural network (BPNN) to optimize the security risk assessment model. A key challenge of researching community security risk assessment lies in accurately identifying and predicting a range of potential security threats. These threats may encompass natural disasters, public health crises, accidents, and social security issues. The intricate interplay of these risk factors, combined with the dynamic nature of community environments, presents difficulties for traditional risk assessment methodologies to address effectively. Initially, this paper delves into the factors influencing safety incidents within communities and establishes a comprehensive system of safety risk assessment indicators. Leveraging the adaptable and generalizable nature of the BPNN model, the paper proceeds to optimize the BPNN model, enhancing the security risk assessment model through this optimization. Subsequent comparison experiments with traditional models validate the rationality and effectiveness of the proposed model, with hidden layer nodes set at various levels like 10, 15, 20, 25, 30, and 35. These traditional models include Convolutional Neural Network (CNN), Long Short-Term Memory Network (LSTM), Bidirectional Encoder Representations from Transformers (BERT), Generative Pre-trained Transformer (GPT), and eXtreme Gradient Boosting (XGBOOST). Experimental findings demonstrate that with 20 hidden layer nodes, the optimized model achieves a remarkable final recognition accuracy of 99.1 %. Moreover, the optimized model exhibits significantly lower final function loss compared to models with different node numbers. Increasing the number of hidden layer nodes may diminish the optimized model's fit and accuracy. Comparison with traditional models reveals that the average accuracy of the optimized model in community risk identification reaches 98.5 %, with a maximum accuracy of 99.6 %. This marks an improvement of 9%-11 % in recognition accuracy across various risk factors compared to traditional models. Regarding system response time and resource utilization, the optimized model exhibits a response time ranging from 100 ms to 120 ms and consistently lower resource utilization rates across all scenarios, underscoring its efficiency in community security risk assessment. In conclusion, this experiment sheds light on the underlying mechanisms and patterns of community safety risk formation, offering novel perspectives and methodologies for researching community safety risk assessment. The paper concludes by presenting recommendations and strategies for addressing community safety risks based on experimental analysis.

The role of kinases in peripheral nerve regeneration: mechanisms and implications.

Peripheral nerve injury disease is a prevalent traumatic condition in current medical practice. Despite the present treatment approaches, encompassing surgical sutures, autologous nerve or allograft nerve transplantation, tissue engineering techniques, and others, an effective clinical treatment method still needs to be discovered. Exploring novel treatment methods to improve peripheral nerve regeneration requires more effort in investigating the cellular and molecular mechanisms involved. Many factors are associated with the regeneration of injured peripheral nerves, including the cross-sectional area of the injured nerve, the length of the nerve gap defect, and various cellular and molecular factors such as Schwann cells, inflammation factors, kinases, and growth factors. As crucial mediators of cellular communication, kinases exert regulatory control over numerous signaling cascades, thereby participating in various vital biological processes, including peripheral nerve regeneration after nerve injury. In this review, we examined diverse kinase classifications, distinct nerve injury types, and the intricate mechanisms involved in peripheral nerve regeneration. Then we stressed the significance of kinases in regulating autophagy, inflammatory response, apoptosis, cell cycle, oxidative processes, and other aspects in establishing conductive microenvironments for nerve tissue regeneration. Finally, we briefly discussed the functional roles of kinases in different types of cells involved in peripheral nerve regeneration.

Using case-based learning supported by role-playing situational teaching method in endocrine physiology education.

Embedding clinically relevant learning experience to basic science subjects is desired for the preclinical phase of the undergraduate medical education. The present study aims to modify case-based learning (CBL) with role-playing situational teaching method and assess the student feedback and learning effect. 176 sophomore students majoring in clinical medicine from Harbin Medical University were randomly divided into two groups: the control group (n=90) who received the traditional hybrid teaching, and the experimental group (n=86), who received the role-playing situational teaching. Students in the experimental group were given a one-week pre-class preparation to dramatize a hyperthyroidism scenario through online autonomous learning of thyroid physiology, and performed the patient's consultation process in class, followed by a student presentation about key points of lecture content and a question-driven discussion. A posttest and questionnaire survey were conducted after class. The test scores of the two groups had no statistical differences, whereas the rate of excellence (high scores) of the experimental group was significantly higher than that of the control group. Furthermore, the record of online self-directed learning engagements was significantly improved in the experimental group. In the questionnaire, more than 70% of the students showed positive attitudes towards the role-playing situational teaching method and were willing to participate in other chapters of the physiology course. Such results show that CBL supported by role-playing situational teaching method encourages active learning and improves the application of basic knowledge of physiology, which can be incorporated in the preclinical curriculums to bridge the gap between theory and practice.

Modifying soil bacterial communities in saline mudflats with organic acids and substrates.

Aims: The high salinity of soil, nutrient scarcity, and poor aggregate structure limit the exploitation and utilization of coastal mudflat resources and the sustainable development of saline soil agriculture. In this paper, the effects of applying exogenous organic acids combined with biological substrate on the composition and diversity of soil bacterial community were studied in moderately saline mudflats in Jiangsu Province. Methods: A combination of three exogenous organic acids (humic acid, fulvic acid, and citric acid) and four biological substrates (cottonseed hull, cow manure, grass charcoal, and pine needle) was set up set up on a coastal saline mudflat planted with a salt-tolerant forage grass, sweet sorghum. A total of 120 kg ha-1 of organic acids and 5,000 kg ha-1 of substrates were used, plus two treatments, CK without application of organic acids and substrates and CK0 in bare ground, for a total of 14 treatments. Results: No significant difference was found in the alpha diversity of soil bacterial community among all treatments (p ≥ 0.05), with the fulvic acid composite pine needle (FPN) treatment showing the largest increase in each index. The beta diversity differed significantly (p < 0.05) among all treatments, and the difference between citric acid-grass charcoal (CGC) and CK treatments was greater than that of other treatments. All treatments were effective in increasing the number of bacterial ASVs and affecting the structural composition of the community. Citric acid-cow manure (CCM), FPN, and CGC treatments were found to be beneficial for increasing the relative abundance of Proteobacteria, Chloroflexi, and Actinobacteria, respectively. By contrast, all treatments triggered a decrease in the relative abundance of Acidobacteria. Conclusion: Among the 12 different combinations of exogenous organic acid composite biomass substrates applied to the coastal beach, the CGC treatment was more conducive to increasing the relative abundance of the salt-tolerant bacteria Proteobacteria, Chloroflexi and Actinobacteria, and improving the community structure of soil bacteria. The FPN treatment was more conducive to increase the species diversity of the soil bacterial community and adjust the species composition of the bacterial community.

Nitrogen Effects Endowed by Doping Electron-Withdrawing Nitrogen Atoms into Polycyclic Aromatic Hydrocarbon Fluorescence Emitters.

Unveiling innovative mechanisms to design new highly efficient fluorescent materials and, thereby, fabricate high-performance organic light-emitting diodes (OLEDs) is a concerted endeavor in both academic and industrial circles. Polycyclic aromatic hydrocarbons (PAHs) have been widely used as fluorescent emitters in blue OLEDs, but device performances are far from satisfactory. In response, we propose the concept of "nitrogen effects" endowed by doping electron-withdrawing nitrogen atoms into PAH fluorescence emitters. The presence of the n orbital on the imine nitrogen is conducive to promoting electron coupling, which leads to increased molar absorptivity and an accelerated radiative decay rate of emitters, thereby facilitating the Förster energy transfer (FET) process in the OLEDs. Additionally, electronically withdrawing nitrogen atoms enhances host-guest interactions, thereby positively affecting the FET process and the horizontal orientation factor of the emitting layer. To validate the "nitrogen effects" concept, cobalt-catalyzed multiple C-H annulation has been utilized to incorporate alkynes into the imine-based frameworks, which enables various imine-embedded PAH (IE-PAH) fluorescence emitters. The cyclization demonstrates notable regioselectivity, thereby offering a practical tool to precisely introduce peripheral groups at desired positions with bulky alkyl units positioned adjacent to the nitrogen atoms, which were previously beyond reach through the Friedel-Crafts reaction. Blue OLEDs fabricated with IE-PAHs exhibit outstanding performance with a maximum external quantum efficiency (EQEmax) of 32.7%. This achievement sets a groundbreaking record for conventional blue PAH-based fluorescent emitters, which have an EQEmax of 24.0%.

Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials.

Objectives: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC. Methods: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0. Results: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate. Conclusions: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

Identification of key molecules in the formation of portal vein tumor thrombus in hepatocellular carcinoma based on single cell transcriptomics and in vitro experiments.

Background: The presence of portal vein tumor thrombus (PVTT) is a significant indicator of advanced-stage hepatocellular carcinoma (HCC). Unfortunately, the prediction of PVTT occurrence remains challenging, and there is a lack of comprehensive research exploring the underlying mechanisms of PVTT formation and its association with immune infiltration. Methods: Our approach involved analyzing single-cell sequencing data, applying high dimensional weighted gene co-expression network analysis (hdWGCNA), and identifying key genes associated with PVTT development. Furthermore, we constructed competing endogenous RNA (ceRNA) networks and employed weighted gene co-expression network analysis (WGCNA), as well as three machine-learning techniques, to identify the upstream regulatory microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) of the crucial mRNAs. We employed fuzzy clustering of time series gene expression data (Mfuzz), gene set variation analysis (GSVA), and cell communication analysis to uncover significant signaling pathways involved in the activation of these important mRNAs during PVTT development. In addition, we conducted immune infiltration analysis, survival typing, and drug sensitivity analysis using The Cancer Genome Atlas (TCGA) cohort to gain insights into the two patient groups under study. Results: Through the implementation of hdWGCNA, we identified 110 genes that was closely associated with PVTT. Among these genes, TMEM165 emerged as a crucial candidate, and we further investigated its significance using COX regression analysis. Furthermore, through machine learning techniques and survival analysis, we successfully identified the upstream regulatory miRNA (hsa-miR-148a) and lncRNA (LINC00909) that targeted TMEM165. These findings shed light on the complex regulatory network surrounding TMEM165 in the context of PVTT. Moreover, we conducted CIBERSORT analysis, which unveiled correlations between TMEM165 and immune infiltration in HCC patients. Specifically, TMEM165 exhibited associations with various immune cell populations, including memory B cells and CD8+ T cells. Additionally, we observed implications for immune function, particularly in relation to immune checkpoints, within the context of HCC. Conclusions: The regulatory axis involving TMEM165, hsa-miR-148a, and LINC00909 emerges as a crucial determinant in the development of PVTT in HCC patients, and it holds significant implications for prognosis. Furthermore, alterations in the TMEM165/hsa-miR-148a/LINC00909 regulatory axis exhibit a strong correlation with immune infiltration within the HCC tumor microenvironment, leading to immune dysfunction and potential failure of immunotherapy.

Artificial neural network optimisation of natural deep eutectic solvent extraction process of Danshen-Gegen and cytotoxicity study.

Natural deep eutectic solvents (NaDESs) are environmentally friendly and efficient for the componential extraction of traditional Chinese medicine compared to conventional organic solvents. In this study, NaDES was screened and employed to extract Danshen-Gegen (DG), and the extraction process was optimised by response surface methodology (RSM) and artificial neural networks (ANN) model. Besides, the in vitro security of extracts of DG were evaluated in PC12 cells. As a result, Betaine-Urea (Bet-Ur) was screened as extraction solvent and ANN model was more accurate than RSM model in optimising the extraction parameter. The extraction process optimised by ANN was as follows: 70% NaDES concentration, 80 mg/mL solid to liquid ratio, 67 °C ultrasonic temperature, and 33 min of ultrasonic time. The comprehensive value of extraction yield was 0.7251 ± 0.84%. IC50 of Bet-Ur, NaDES DG extract and aqueous DG extract were 0.15%, 0.3% and 10% (v/v).

Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity.

BACKGROUND: Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. METHODS: A Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. RESULTS: Of 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25-75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. CONCLUSIONS: Serum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.

Biochar boosted high oleic peanut production with enhanced root development and biological N fixation by diazotrophs in a sand-loamy Primisol.

Peanut yield and quality face significant threats due to climate change and soil degradation. The potential of biochar technology to address this challenge remains unanswered, though biochar is acknowledged for its capacity to enhance the soil microbial community and plant nitrogen (N) supply. A field study was conducted in 2021 on oil peanuts grown in a sand-loamy Primisol that received organic amendments at 20 Mg ha-1. The treatments consisted of biochar amendments derived from poultry manure (PB), rice husk (RB), and maize residue (MB), as well as manure compost (OM) amendment, compared to no organic amendment (CK). In 2022, during the second year after amendment, samples of bulk topsoil, rooted soil, and plants were collected at the peanut harvest. The analysis included the assessment of soil quality, peanut growth traits, microbial community, nifH gene abundance, and biological N fixation (BNF) rate. Compared to the CK, the OM treatment led to an 8 % increase in peanut kernel yield, but had no effect on kernel quality in terms of oil production. Conversely, both PB and MB treatments increased kernel yield by 10 %, whereas RB treatment showed no change in yield. Moreover, all biochar amendments significantly improved oilseed quality by 10-25 %, notably increasing the proportion of oleic acid by up to 70 %. Similarly, while OM amendment slightly decreased root development, all biochar treatments significantly enhanced root development by over 80 %. Furthermore, nodule number, fresh weight per plant, and the nifH gene abundance in rooted soil remained unchanged under OM and PB treatments but was significantly enhanced under RB and MB treatments compared to CK. Notably, all biochar amendments, excluding OM, increased the BNF rate and N-acetyl-glucosaminidase activity. These changes were attributed to alterations in soil aggregation, moisture retention, and phosphorus availability, which were influenced by the diverse physical and chemical properties of biochars. Overall, maize residue biochar contributed synergistically to enhancing soil fertility, peanut yield, and quality while also promoting increased root development, a shift in the diazotrophic community and BNF.

Assisted reproductive technology and neurodevelopment in children at one year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at one year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3,531 pregnancies with 3,840 cohort children who completed neurodevelopment assessment at one year of age, including 1,906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24%-34% decrease in the risk for noncompetent development in three domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSIONS: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Genome Mining Leads to Diverse Sesquiterpenes with Anti-inflammatory Activity from an Arctic-Derived Fungus.

With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypella sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7 possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15 exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8 inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8 also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.

Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Dynamic assessment of community resilience in China: empirical surveys from three provinces.

Background: Strengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China. Methods: A community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled. Results: The results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p < 0.05). In 2015, connection and caring achieved the highest score, while disaster management achieved the highest score in 2022, with resources and transformative potential ranking the lowest in their scores in both years. Generally, residents presented a high awareness of disaster risks. However, only a small proportion of residents that were surveyed had participated in any "community-organized epidemic prevention and control voluntary services" (34.9%). Analysis shows that core influencing factors of community resilience include: High sensitivity towards major epidemic-related information, particular attention to various kinds of epidemic prevention and control warning messages, participation in epidemic prevention and control voluntary services, and formulation of epidemic response plans. In this study, we have constructed Community Resilience Governance System Framework in China, which included community resilience risk awareness, community resilience governance bodies, community resilience mechanisms and systems. Conclusion: During the pandemic, community resilience in China underwent significant changes. However, community capital was, is, and will be a weak link to community resilience. It is suggested that multi-stages assessments of dynamic change trends of community resilience should be further performed to analyze acting points and core influencing factors of community resilience establishment at different stages.