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Despite their importance as components for flexible electronics, most stretchable hydrogels suffer from incomplete recovery after deformation, are prone to failure upon long-term repeated stretching, and cannot be exploited at subzero temperatures because of the freezing of their constituent water. Consequently, strategies for circumventing these drawbacks are highly sought after. This study describes the synthesis of a doubly (chemically and physically) crosslinked hydrogel from gelatin and methacrylic acid and demonstrates the suitability of this material for the fabrication of high-performance stretchable and environment-resistant supercapacitors and strain sensors. The performance of this supercapacitor (areal capacitance = 1,210.2 mF/cm2 at a current density of 1 mA/cm2, maximum energy density = 158.8 μW⋅h/cm2, maximum power density = 659.5 μW/cm2) was superior to that of most of integrated supercapacitors reported to date and was hardly affected by stretchable, low temperatures, bending, ice-cold water and strong acid/alkali solutions or long-term storage. Additionally, a strain sensor based on the above hydrogel was capable of accurately capturing human body motions when affixed to skin and recognising mouse movement (even in humid environments) after implantation into mouse legs. Our work may pave the way to high-performance stretchable and environment-resistant wearable electronics.

Abstract This paper addresses the energy management control problem of solar power generation system by using the data-driven method. The battery-supercapacitor hybrid energy storage system is considered to smooth the power fluctuation. A new model-free control method is utilized in the stand-alone photovoltaic DC-microgrid to provide the power to meet the demand load, while guaranteeing the DC bus voltage is stable. Furthermore, the proposed data-based power management control strategy only needs I/O data. Numerical simulations with real data verify the effectiveness of the proposed method.

Abstract Background The diagnosis of peripheral isolated nodular lesions that are suspected as pulmonary tuberculosis (PTB) is challenging, which are not easily accessible via conventional bronchoscopy. This study evaluated the combined use of Xpert MTB/RIF assay and endobronchial ultrasonography with a guide sheath (EBUS-GS) for detecting MTB infection in peripheral lung bands, for early detection of PTB. Methods The clinical data of 232 patients with suspected peripheral nodular PTB who underwent EBUS-GS between June 2020 and October 2023 were retrospectively reviewed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of acid-fast bacilli smear, culture, Xpert MTB/RIF assay, and pathological examination were calculated. To assess diagnostic accuracy, the results of the four methods were directly compared with the final clinical diagnosis. Results In total, 146 and 86 patients were clinically diagnosed with peripheral nodular PTB and non-PTB, respectively. The sensitivity, specificity, PPV, NPV, and AUC values of combined Xpert MTB/RIF assay and EBUS-GS were 47.26%, 100.0%, 100.0%, 52.76%, and 0.74; those of acid-fast bacilli smear were 8.22%, 97.67%, 85.71%, 38.53%, and 0.53; those of culture were 31.51%, 100.0%, 100.0%, 46.24%, and 0.66; and those of pathological examination were 23.97%, 97.67%, 94.59%, 43.08%, and 0.61, respectively. Conclusion The diagnostic accuracy of the combined Xpert MTB/RIF assay and EBUS-GS was significantly better than that of other conventional tests. Hence, this novel technique can be routinely applied for diagnosing and managing peripheral nodular PTB.

Abstract Background This paper reviews the scope of research on kinesiophobia in patients after cardiac surgery. Further, it reviews the current situation, evaluation tools, risk factors, adverse effects, and intervention methods of kinesiophobia to provide a reference for promoting early rehabilitation of patients after cardiac surgery. Methods Guided by the scoping methodology, the Web of Science, PubMed, CINAHL, Cochrane Library, China Biomedical Literature Database, VIP Database, Wanfang Database, CNKI, and other databases were searched from database inception until July 31, 2024. The studies obtained were screened, summarised and systematically analysed by two researchers. Results Eighteen studies (16 cross-sectional studies, one qualitative study, and one randomised controlled trial) were included. The incidence of kinesiophobia in patients after cardiac surgery was 39.20–82.57%, and the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to evaluate this incidence. The influencing factors of kinesiophobia in patients after cardiac surgery included demographic characteristics, pain severity, frailty, exercise self-efficacy, disease-related factors, and psychosocial factors. Kinesiophobia led to adverse health outcomes such as reduced recovery, prolonged hospital stays, and decreased quality of life in patients after cardiac surgery, and there were few studies on intervention methods for postoperative kinesiophobia. Conclusion The kinesiophobia assessment tools suitable for patients after cardiac surgery should be improved, and intervention methods to promote the early recovery of patients after major clinical surgery and those with difficult and critical diseases should be actively researched.

Abstract Background NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. Methods Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. Results Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1β (IL-1β), alongside decreased activation of NLRP3 inflammasome and IL-1β secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. Conclusion This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

Abstract Background Microbiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules. Methods This was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve. Results A total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826). Conclusion EBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.

Abstract With an increasing affinity towards patient‐centric care, sharing real‐time sensitive data for collaboration between multiple parties with finer access control becomes critical. Most existing studies based on the blockchain technology in the medical field discuss various application scenarios and security aspects, without focusing on data ownership, secure data sharing, or finer access control. In this work, a non‐fungible token (NFT)‐based system is proposed to implement a health record marketplace. The system leverages the NFT technology to provide dual ownership along with finer access control and efficiency in data sharing. The advantage of permissioned blockchain along with InterPlanetary File System (IPFS) are taken for off‐chain data storage to improve security and efficiency. Because price determination is critical in the market, Stackelberg game theory is utilized to determine pricing strategies for both data owners and consumers. Also, to efficiently achieve finer access control, a popularity‐based adaptive NFT management scheme using reinforcement learning is proposed. Simulation experiments are carried out to demonstrate accuracy and efficiency of our proposed schemes.

Cerebral veins are responsible for the outflow drainage of brain interstitial fluid (ISF). The importance of cerebral venous drainage has been emphasized in various neurological diseases. Impaired venous outflow may lead to brain edema, blood–brain barrier (BBB) disruption, inflammatory responses and hemorrhagic complications. With the development of imaging technologies, several imaging-based signs for venous assessment are proposed. Therapies targeting cerebral venous drainage have shown beneficial outcomes in cerebral venous sinus thrombosis (CVST) in clinic, however more insight into the cellular and molecular level should be elucidated. Here we review the pathological changes following cerebral venous drainage impairment, summary the advances in image-based evaluation, address the potential molecular mechanisms, and discuss venous drainage-focused therapies. A better understanding of cerebral venous drainage and its underlying mechanism will promote the pharmacological development and clinical management of CVST.

BackgroundsDupilumab has demonstrated remarkable efficacy and safety in clinical trials for moderate-to-severe atopic dermatitis (AD). However, long-term real-world evidence, especially in the Chinese population, remains limited.ObjectiveTo investigate the long-term efficacy and safety of dupilumab for moderate-to-severe AD in a real-world clinical setting in China and analyze factors that may influence its long-term treatment outcomes.MethodsThis prospective, observational real-world study included moderate-to-severe AD patients from the AD cohort of the dermatology department of Chongqing Hospital of Traditional Chinese Medicine who received dupilumab treatment for≥52 weeks. Efficacy and adverse events were assessed at baseline, weeks 4, 16, 24, and 52. Multivariate logistic regression analysis was used to identify predictive factors for achieving EASI 50 and EASI 75 at week 52.ResultsA total of 124 patients were included. At week 52, EASI, SCORAD, IGA, NRS, and DLQI scores were significantly improved compared to baseline. The proportions of patients achieving EASI-50/75 were 50.81%/29.84%, 72.58%/42.74%, 75%/53.23%, and 67.74%/41.94% at weeks 4, 16, 24 and 52, respectively. Female sex, absence of atopic comorbidities, higher baseline EASI, and medication compliance were positive predictive factors for 52-week EASI-50/75. Eosinophil elevation predicted lower EASI-50 attainment. Nineteen adverse events occurred during the 52-week period (incidence rate: 14.52%), mostly mild and manageable.ConclusionsDupilumab demonstrated significant efficacy and a low incidence of adverse events over 52 weeks in Chinese patients with moderate-to-severe AD, making it an effective and safe long-term treatment option. Predictive factors were identified to guide treatment optimization.

Objective: This study aims to investigate the current status and trends of pressure ulcer care studies over the past two decades using bibliometric and visual analysis, with the objective of providing guidelines for the development of relevant clinical practices or further research. Methods: We conducted a search on the Web of Science Core Collection database using the subject terms “pressure ulcers” or “pressure injuries” for the period from January 2002 to December 2021. Bibliometric tools such as CiteSpace (version 5.8.R3), VOS viewer (version 1.6.17) and the R software 4.0.3 were used to visualize and analyze annual publications, country, institution, author, keyword and cited literature. Results: We identified 5102 publications related to pressure ulcers during the 20-year period, including 4034 articles published in 1557 journals. The number of annual publications on the relevant topics has been increasing annually at an annual growth rate of 4.89 %. The keyword cluster analysis of these studies can be divided into four areas: epidemiology, risk assessment, caring intervention and prognostic analysis. Keyword temporal analysis revealed that the “Braden score” was the most commonly used keyword over a long-term span. The dissemination of knowledge and student training on pressure ulcers have become hot topics of research in recent years. Additionally, pressure ulcer care in COVID-19 patients has emerged as another research hotspot due to the pandemic. Conclusion: Bibliometric analyses have shown that there has been a steady increase in research on pressure ulcer care, with studies related to pressure ulcer risk scores accounting for a large portion of this research. In recent years, education on pressure ulcer-related knowledge and pressure ulcer care in COVID-19 patients have emerged as research hotspots. Future research on pressure ulcer care in the elderly may be a research hotspot as the aging population progresses.

Abstract The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Abstract Rice blast, caused by Magnaporthe oryzae (M. oryzae), is one of the most common and damaging diseases of rice that limits rice yield and quality. The mediator complex plays a vital role in promoting transcription by bridging specific transcription factors and RNA polymerase II. Here, we show that the rice mediator subunit OsMED16 is essential for full induction of the diterpenoid phytoalexin biosynthesis genes and resistance to the ascomycetous fungus M. oryzae. Mutants of Osmed16 show reduced expression of the DP biosynthesis genes and are markedly more susceptible to M. oryzae, while transgenic plants overexpressing OsMED16 increased the expression of the DP biosynthesis genes and significantly enhanced resistance to M. oryzae. Interestingly, OsMED16 is physically associated with the WRKY family transcription factor OsWRKY45, which interacts with the phytoalexin synthesis key regulator transcription factor OsWRKY62. Further, OsMED16-OsWRKY45-OsWRKY62 complex could bind to the promoter regions of phytoalexin synthesis-related genes and activate their gene expression. Our results show that OsMED16 may enhance rice tolerance to M. oryzae via directly manipulating phytoalexin de novo biosynthesis.

Abstract The surfaces of lotus leaves with micro- and nano-waxy cuticle structures are superhydrophobic and possess a self-healing ability to regain hydrophobicity after damage. Inspired by this phenomenon, the problem of water-repellent coatings used in natural environments failing to perform after damage can be solved if these coatings are endowed with rapid self-repair and self-growth functions. However, there has been almost no exploration into the hydrophobicity self-repair process in lotus leaves. The changes in surface morphology during the hydrophobicity recovery process are not understood. There is a lack of research on the hydrophobicity recovery in lotus leaves. In this study, the damage and recovery experiments on lotus leaf surfaces were carried out in an artificial climate chamber, and the water repellency recovery process and typical water repellency roughness parameters regained time were obtained. Upon analyzing the differences in the recovery process of different damage types, the recovery mechanism after lotus leaf surface damage was obtained. Finally, it was found that the microscopic roughness determined the static contact angle (WCA) of the lotus leaf surface, and the nanoscopic roughness determined the rolling angle (SA). The dual factors of the recovery of the extruded epidermal tissue and the regeneration of the epidermal wax crystals determined the hydrophobicity recovery process in damaged lotus leaves.

Objective To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB).Methods In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed.Results The Student’s t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models.Conclusion The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.

The linkage between biocides and antibiotic resistance has been widely suggested in laboratories and various environments. However, the action mechanism of biocides on antibiotic resistance genes (ARGs) spread is still unclear. Thus, 6 quaternary ammonium biocides (QACs) with different bonded substituents or alkyl chain lengths were selected to assess their effects on the conjugation transfer of ARGs in this study. Two conjugation models with the same donor (E. coli DH5α (RP4)) into two receptors, E. coli MG1655 and pathogenic S. sonnei SE6-1, were constructed. All QACs were found to significantly promote intra- and inter-genus conjugative transfer of ARGs, and the frequency was highly impacted by their structure and receptors. At the same environmental exposure level (4 × 10-1 mg/L), didecyl dimethyl ammonium chloride (DDAC (C10)) promoted the most frequency of conjugative transfer, while benzathine chloride (BEC) promoted the least. With the same donor, the enhanced frequency of QACs of intra-transfer is higher than inter-transfer. Then, the acquisition mechanisms of two receptors were further determined using biochemical combined with transcriptome analysis. For the recipient E. coli, the promotion of the intragenus conjugative transfer may be associated with increased cell membrane permeability, reactive oxygen species (ROS) production and proton motive force (PMF)-induced enhancement of flagellar motility. Whereas, the increase of cell membrane permeability and decreased flagellar motility due to PMF disruption but encouraged biofilm formation, maybe the main reasons for promoting intergenus conjugative transfer in the recipient S. sonnei. As one pathogenic bacterium, S. sonnei was first found to acquire ARGs by biocide exposure.

Objective This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF).Design Single-centre retrospective study.Setting The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital.Participants We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023.Methods We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM.Results Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively.Conclusion The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

BackgroundThe benefits of home enteral nutrition (HEN) are increasingly recognized, with more scholars focusing on this field. This study aimed to comprehensively identify collaborative networks, analyze, and track research trends, focus on current hotspots, and accurately predict the forefront and focus of home enteral nutrition.MethodsA computer search of the Web of Science Core Collection (WoSCC) was conducted for studies related to home enteral nutrition published from January 1, 2004, to December 31, 2023, and select them in compliance with the PRISMA guidelines. The CiteSpace software was used for bibliometric visualization and comparative analysis of countries, institutions, journals, references, and keywords.ResultsA total of 1,113 documents were included, showing a steady annual increase in publication volume. The United States and the Mayo Clinic were the top publishing country and institution, with 302 and 41 papers, respectively. “CLIN NUTR” had the highest number of publications, totaling 221, while “ESPEN guideline on home enteral nutrition” was the most cited reference, with 43 citations. The most prolific author was Manpreet S with 29 papers.ConclusionThe management of HEN is a current research hotspot. The safety of HEN and how to improve patient compliance are critical areas for researchers to consider. Future research could focus on these aspects. The blurring of boundaries between hospital and home care and how to utilize telemedicine technologies to serve more patients deserve in-depth exploration. Researchers worldwide should combine their unique characteristics and advantages to strengthen international cooperation.

Studies have shown that a lot of traditional Chinese medicines could improve the immunity of the body. Dangdi oral liquid (DDO) was mainly composed of Angelica sinensis (Oliv.) Diels (Danggui), Rehmannia glutinosa Libosch. (Dihuang), Achyranthes bidentata Bl. (Niuxi), Glycyrrhiza uralensis Fisch. (Gancao). In this study, the rapid ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to identify the potentially effective compounds of DDO. Then the immune activity of DDO was measured by lymphocyte proliferation, macrophage phagocytic function, NK cell activity, delayed type hypersensitivity reaction, hemolytic plaque number, sIgA content and immune organ index. The results showed that a total of 51 compounds were identified. In addition, DDO could significantly promote the lymphocyte proliferation, improve macrophage phagocytic ability, NK cell activity, hemolytic plaque number, sIgA content and immune organ index compared with control group, and the medium dose possessed the best efficacy (P＜0.05). These results indicated that DDO could enhance the immunity of mice.

Summary: Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing. The Recursive Feature Elimination Cross-Validation and deep neural network algorithm established the CanDo classification model, which incorporated 11 methylation features (including 8 specific to the TBR1 gene), demonstrating a sensitivity of 98.6% and specificity of 97.8%. In contrast, bronchoscopic rapid on-site evaluation (bronchoscopic-ROSE) had lower sensitivity (87.7%) and specificity (80%). Further validation in 33 individuals confirmed CanDo’s discriminatory potential, particularly in challenging cases for bronchoscopic-ROSE due to pathological complexity. CanDo serves as a valuable complement to bronchoscopy for the discriminatory diagnosis and stratified management of lung tumors utilizing BWF specimens.

As a climate-sensitive region， precipitation over the Qinghai-Xizang （Tibetan） Plateau significantly impacts the water cycle and the climate of East Asia.Therefore， it is important to study its changes.Precipitation is an important variable in the global hydrological cycle and one of the major climate systems affected by climate change.To investigate the ability of the global climate models to simulate precipitation over the Qinghai-Xizang （Tibetan） Plateau and examine possible changes in future precipitation under the new model and scenarios， this paper uses the latest monthly precipitation data from the 31 climate models of the Coupled Model Intercomparison Project 6 （CMIP6） and the CN05.1 precipitation observation data set provided by the National Climate Center to evaluate the ability of the CMIP6 model to simulate precipitation over the Qinghai-Xizang （Tibetan） Plateau.Furthermore， better models are selected to project the future precipitation of the Qinghai-Xizang （Tibetan） Plateau under different Shared Socioeconomic Pathway （SSP） scenarios.The results show that the model distribution of observed precipitation over the Qinghai-Xizang （Tibetan） Plateau from 1995 to 2014 is characterized by a decrease from southeast to northwest and a summer precipitation concentration.Most of the models can simulate the precipitation distribution and seasonal trend， but almost all of them overestimate the precipitation phenomenon， and the average precipitation of multiple modes is 102% higher than that observed.In general， the latest model of CMIP6 has a poor ability to simulate precipitation over the Qinghai-Xizang （Tibetan） Plateau， and the average relative deviation index of the model from the observation is 102%， indicating that most of the models are not satisfactory， and EC-Earth3-Veg-LR， MPI-ESM1-2-LR， EC-Earth3-Veg， and MRI-ESM2-0 are selected as the better modes after quantitative analysis of all the models， which can roughly reflect the precipitation characteristics of the Qinghai-Xizang （Tibetan） Plateau.Climate models show the slowest increase of precipitation over the Qinghai-Xizang （Tibetan） Plateau under the SSP1-2.6 scenario and the fastest increase under SSP5-8.5.From SSP1-2.6 in the small radiative forcing scenario to SSP5-8.5 in the large scenario， the recent （from 2021 to 2040） precipitation increase on the plateau is difficult to find a large difference in each scenario， but there is a significant increase in the mid （from 2041 to 2060） and late （from 2081 to 2100） scenarios， indicating that carbon emission intensity has a small impact in the short term and a large impact in the long term.The future increase in precipitation mainly occurs in the area south of the Nianqing Tanggula Mountains， from a seasonal point of view， the summer increase is the largest， followed by spring and autumn， the smallest increase is in winter， so we should pay attention to the future summer and spring precipitation changes over the Qinghai-Xizang （Tibetan） Plateau and take coping measures.

As electric vehicles rapidly gain popularity, battery swapping stations have emerged as key infrastructure to enhance the convenience of electric vehicles. Accurately estimating the State of Charge (SOC) of batteries during the battery swapping process is critical for ensuring efficient operation and optimizing battery management. This paper proposes a digital twin framework and establishes a data-driven model for SOC estimation. The model, Ensemble Weighted Network (EWN), is embedded in the digital twin framework. It has three remarkable processes: multi-model ensemble, accuracy weight scaling, and time weight scaling. The multi-model ensemble combines five popular SOC estimating learners, to avoid the accuracy limitations of a single estimation model. The accuracy weight scaling and time weight scaling strategies are put forward to assign appropriate weights to each model, addressing significant fluctuations in estimation capability among different models across various periods. The results show the root mean square error, mean absolute error, and mean absolute percentage error of the model are less than 1.10%, 0.96%, and 1.92% respectively. Furthermore, we conduct experiments on public datasets to prove the proposed model has high estimation accuracy and robustness for different temperatures and battery types. Finally, the visualization of the digital twin is built, allowing operators to monitor and manage the batteries.

Abstract Air gap impulse discharge characteristics of railway tunnel‐catenary at high‐altitude are of great significance to the electrical insulation design. The existing altitude correction methods for non‐uniform air gaps are not applicable to tunnel‐catenary. To investigate the impulse discharge characteristics of the tunnel‐catenary, a typical structural model was built in an artificial climate chamber. Different altitudes were simulated by adjusting the atmospheric pressure. The 50% breakdown voltages of the 300–700 mm tunnel‐catenary gap were tested at 243–4000 m. The test found that the altitude/atmospheric pressure and gap length have an evident effect on the 50% impulse breakdown voltage, and the influence of humidity is relatively small. The polarity effect was analysed by streamer theory. The {d, P, h} parameter method was employed to obtain the fitting formulas for the impulse breakdown voltage. A high‐altitude correction method for the tunnel‐catenary breakdown voltage based on 1 km altitude was proposed. Field natural tests were conducted to verify the accuracy of the proposed method. The results show that the breakdown voltage obtained by the correction method has an average error of 3.66% in the results of the field tests, indicating that the method has engineering application prospects.

Abstract Background Sepsis is a severe syndrome of organ dysfunction that often leads to cardiac dysfunction and endangers life. The role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in LPS-induced myocardial injury is unclear. The purpose of this study was to assess the role of ALDH2 in lipopolysaccharide (LPS)-induced myocardial injury and the regulatory mechanism and to identify potential therapeutic strategies for treating this condition. Methods An in vivo model was established by 12 h of LPS (10 mg/kg, intraperitoneal injection) stimulation, and an in vitro model was generated by stimulating H9C2 cells with LPS (10 μg/ml) for 12 h. We then used the ALDH2 activator Alda-1 and the ALDH2 inhibitor daidzin to assess their effects on LPS-induced cardiac injury. Cardiac function in mice was evaluated by using cardiac ultrasound. We used various methods to evaluate inflammation, apoptosis, and oxidative stress, including ELISA, flow cytometry, JC-1 staining, Western blotting, and DCFH-DA staining. Additionally, we used a small interfering RNA (siRNA) to knock down cyclic GMP-AMP synthase (cGAS) to further investigate the relationship between ALDH2 and cGAS in LPS-induced cardiac injury. Results LPS-induced cardiac dysfunction and increased the levels of the cardiac injury markers creatine kinase-MB (CKMB) and lactate dehydrogenase (LDH) in vivo. This change was accompanied by an increase in reactive oxygen species (ROS) levels, which exacerbated the oxidative stress response and regulated apoptosis through cleaved caspase-3, BAX, BCL-2. The expression of inflammatory cytokines such as IL-6/IL-1β/TNF-α was also upregulated. However, these effects were reversed by pretreatment with Alda-1 via the inhibition of cGAS/stimulator of interferon genes (STING) signaling pathway. Interestingly, LPS, Alda-1 and daidzin altered the activity of ALDH2 but did not regulate its protein expression. Knocking down cGAS in H9C2 cardiomyocytes alleviated LPS-induced cardiac inflammation, apoptosis, and ROS production and weakened the synergistic effect of daidzin. Conclusion We demonstrated that ALDH2 alleviated LPS-induced cardiac dysfunction, inflammation, and apoptosis through the cGAS/STING signaling pathway, thereby protecting against LPS-induced cardiac injury. This study identifies a novel therapeutic approach for treating sepsis-induced cardiomyopathy (SIC).

Abnormal heating will reduce the insulation performance of composite insulators or even cause insulator fracture, and the abnormal heating phenomenon is more serious under high-humidity conditions. Therefore, in this paper, the voltage withstand test of abnormal heating composite insulators caused by aging and damp sheath, decay-like core rod, and contamination were carried out under different ambient humidity. The heating and discharge of composite insulators were observed by infrared thermal imager and ultraviolet imager, and its temperature characteristics were analyzed from the aspects of heating range, heating shape, and temperature difference. In addition, in order to study the abnormal heating mechanism of composite insulators, the micro-morphology, chemical groups and dielectric properties of the silicon rubber of composite insulators with aging and damp sheath and the decay-like core rod were also measured. It is found that the temperature characteristics of the three types of abnormal heating composite insulators are different, and the temperature difference increases with the increase of humidity. The deterioration of silicone rubber and core rod material is the internal reason for the abnormal heating of composite insulators, and high-humidity conditions will exacerbate the heating phenomenon.

Background/Objectives: Physiologically based pharmacokinetic (PBPK) absorption models are instrumental for assessing drug absorption prior to clinical food effect studies, though discrepancies in predictive and actual outcomes are observed. This study focused on immediate release formulations of weakly basic water-insoluble compounds, namely rivaroxaban, ticagrelor, and PB-201, to investigate factors that could improve the predictive accuracy of PBPK models regarding food effects. Methods: Comprehensive in vitro experimental results provided the basis for the development of mechanistic absorption models, which were then combined with mechanistic disposition models to predict the systemic exposure of the model drugs in both fasted and fed states. Results: The developed PBPK models showed moderate to high predictive accuracy for food effects in Caucasian populations. For the Chinese population, the ticagrelor model’s initial overestimation of fed-state absorption was addressed by updating the permeability parameters from Caco-2 cell assays to those derived from parallel artificial membrane permeability assays in FaSSIF and FeSSIF media. This refinement was also applied to the rivaroxaban and ticagrelor models, leading to a more accurate representation of absorption in Caucasians. Conclusions: This study highlights the importance of apparent permeability in enhancing the predictive accuracy of PBPK absorption models for weakly basic water-insoluble compounds. Furthermore, the precipitation of PB-201 in the two-stage transfer experiments suggests that precipitation may not be a universal phenomenon for such compounds in vivo. Consequently, the precipitation rate constant, a theoretically essential parameter, should be determined based on experimental evidence to avoid overparameterization and ensure robust predictive accuracy of PBPK models.

Abstract Verticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production.

Abstract Background Abnormally regulated long non-coding RNAs (lncRNAs) functions in cancer emphasize their potential to serve as potential targets for cancer therapeutic intervention. LncRNA ASBEL has been identified as oncogene and an anti-sense transcript of tumor-suppressor gene of BTG3 in triple-negative breast cancer (TNBC). Results Herein, multicomponent self-assembled polyelectrolyte nanocomplexes (CANPs) based on the polyelectrolytes of bioactive hyaluronic acid (HA) and chitosan hydrochloride (CS) were designed and prepared for the collaborative modulation of oncogenic lncRNA ASBEL with antago3, an oligonucleotide antagonist targeting lncRNA ASBEL and hydrophobic curcumin (Cur) co-delivery for synergetic TNBC therapy. Antago3 and Cur co-incorporated CANPs were achieved via a one-step assembling strategy with the cooperation of noncovalent electrostatic interactions, hydrogen-bonding, and hydrophobic interactions. Moreover, the multicomponent assembled CANPs were ulteriorly decorated with a near-infrared fluorescence (NIRF) Cy-5.5 dye (FCANPs) for synchronous NIRF imaging and therapy monitoring performance. Resultantly, MDA-MB-231 cells proliferation, migration, and invasion were efficiently inhibited, and the highest apoptosis ratio was induced by FCANPs with coordination patterns. At the molecular level, effective regulation of lncRNA ASBEL/BTG3 and synchronous regulation of Bcl-2 and c-Met pathways could be observed. Conclusion As expected, systemic administration of FCANPs resulted in targeted and preferential accumulation of near-infrared fluorescence signal and Cur in the tumor tissue. More attractively, systemic FCANPs-mediated collaborative modulating lncRNA ASBEL/BTG3 and Cur co-delivery significantly suppressed the MDA-MB-231 xenograft tumor growth, inhibited metastasis and extended survival rate with negligible systemic toxicity. Our present study represented an effective approach to developing a promising theranostic platform for combating TNBC in a combined therapy pattern.

Objective: To investigate the evolution of inflammation under conditions and the effects of ginsenosides on macrophages subjected to the simulated weightlessness, with the aim of mitigating the inflammation. Methods: Initially, genes related to weightlessness, inflammation, and immunity were identified in the GeneCards database. Then, Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) protein network analysis was conducted to determine the core targets involved in the weightlessness-induced inflammation. Subsequently, Label-Free Quantitative (LFQ) proteomics was carried out to discern the distinctive genes within ginsenoside-treated Tohoku Hospital Pediatrics-1 (THP-1) cells. Next, utilizing the outcomes of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the biological processes and signaling pathways in which ginsenosides predominately engaged were scrutinized, and the primary targets of ginsenosides in combating weightlessness-induced inflammation were examined. Finally, enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α from lipopolysaccharide (LPS)-induced THP-1 cells under simulated weightlessness conditions, as well as during the weightlessness recovery period following treatment with ginsenosides. Results: A total of 2 933 genes associated with inflammation, 425 genes linked to weightlessness, and 4 564 genes connected to immunity were retrieved from the GeneCards database. Protein-protein interaction (PPI) networks were generated to identify pivotal targets associated with weightlessness-induced inflammation such as IL-1β, IL-6, TNF, and albumin (ALB). It was found that ginsenosides primarily participated in the regulation of various inflammation-related signaling pathways and pathways related to pathogenic microorganism infections. Moreover, it has a significant impact on the expression of proteins such as cluster of differentiation 40 (CD40), IL-1β, and poly ADP-ribose polymerase 1 (PARP1). As revealed in the simulated weightlessness cell test, ginsenosides exhibited a remarkable capacity to attenuate the secretion of inflammatory factors, specifically IL-6 and TNF-α (P < 0.000 1), in THP-1 macrophages following induction by LPS under simulated weightlessness conditions. In addition, it reduced the secretion of IL-1β, IL-6, IL-8, and TNF-α (P < 0.000 1) during the weightlessness recovery phase. Conclusion: Weightlessness can disrupt several inflammation-related signaling pathways, but ginsenosides were shown to mitigate the release of various inflammatory factors in macrophages subjected to simulated weightlessness, thereby exerting a protective role against inflammation. This study has laid a theoretical groundwork for further exploring the potential application of ginsenosides in safeguarding against LPS induced inflammation in a weightlessness environment.

The development and utilization of clean energy is becoming more extensive, and wind power generation is one of the key points of this. Occasionally, wind turbines are faced with various extreme environmental impacts such as icing, lightning strikes and so on. In particular, the icing of wind turbines increases icing–wind loads, and results in a reduced power output. And blades broken down lead to large-area shutdown accidents caused by high-speed rotating, which seriously affects the reliability and equipment safety of wind power generation. Relevant institutions and researchers at home and abroad have carried out a lot of research on this. This paper summarizes the formation and influencing factors of wind turbine icing, the influence of icing on wind power generation, and defense technologies. First, it introduces the formation conditions and mechanisms of icing in wind farm regions and the relationship between meteorological and climatic characteristics and icing, and analyzes the key influence factors on icing. Then, the impact of icing on wind turbines is explained from the aspects of mechanical operation, the power curve, jeopardies and economic benefits. And then the monitoring and safety status of wind turbines icing is analyzed, which involves collecting the relevant research on anti-de-icing in wind power generation, introducing various anti/de-icing technologies, and analyzing the principle of icing defense. Finally, this paper summarizes wind turbine icing and its defense technologies, and puts forward the future research direction based on the existing problems of wind power generation icing.

Abstract Unclean air discharge refers to the discharge phenomenon of a large number of polluting gases, droplets or solid particles floating in the air, which will cause insulation breakdown and safety accidents for the power transmission equipment that have been left outdoors for a long time. In order to investigate the effects of particle concentration, particle size and dielectric constant on DC breakdown characteristics of unclean air gap, a self‐made discharge chamber was designed in this study. The air was filtered and passed into the discharge chamber to remove the influence of impurities contained in the air on the experimental results. Then, solid particles with different concentration, particle size and particle dielectric constant were added to the discharge chamber to carry out the DC positive polarity breakdown characteristic experiment. The experimental results show that compared with dry clean air, the presence of solid particle increases the breakdown voltage of the gap, and the increase proportion of breakdown voltage is related to the particle concentration, particle size and particle dielectric constant. With the same particle type and particle size, the increase proportion of breakdown voltage increases with the higher concentration, which up to 10.49%. For further investigating, the fluid mechanics model was selected to simulate the process of streamer discharge in unclean air. The results show that compared with dry clean air, the presence of particles enhances the gap discharge ionisation process, but also enhances the adsorption of particles, and the latter has stronger effect than the former, thus increases the gap breakdown voltage. At the same time, the enhancement of adsorption effect increases the electric field intensity of the gap and speeds up the development process of streamer discharge.

Abstract Background Intra-tumoral heterogeneity (ITH) is a distinguished hallmark of cancer, and cancer stem cells (CSCs) contribute to this malignant characteristic. Therefore, it is of great significance to investigate and even target the regulatory factors driving intra-tumoral stemness. c-Myc is a vital oncogene frequently overexpressed or amplified in various cancer types, including breast cancer. Our previous study indicated its potential association with breast cancer stem cell (BCSC) biomarkers. Methods In this research, we performed immunohistochemical (IHC) staining on sixty breast cancer surgical specimens for c-Myc, CD44, CD24, CD133 and ALDH1A1. Then, we analyzed transcriptomic atlas of 1533 patients with breast cancer from public database. Results IHC staining indicated the positive correlation between c-Myc and BCSC phenotype. Then, we used bioinformatic analysis to interrogate transcriptomics data of 1533 breast cancer specimens and identified an intriguing link among c-Myc, cancer stemness and copper-induced cell death (also known as “cuproptosis”). We screened out cuproptosis-related characteristics that predicts poor clinical outcomes and found that the pro-tumoral cuproptosis-based features were putatively enriched in MYC-targets and showed a significantly positive correlation with cancer stemness. Conclusion In addition to previous reports on its oncogenic roles, c-Myc showed significant correlation to stemness phenotype and copper-induced cell toxicity in breast cancer tissues. Moreover, transcriptomics data demonstrated that pro-tumoral cuproptosis biomarkers had putative positive association with cancer stemness. This research combined clinical samples with large-scale bioinformatic analysis, covered description and deduction, bridged classic oncogenic mechanisms to innovative opportunities, and inspired the development of copper-based nanomaterials in targeting highly heterogeneous tumors.

Objectives: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. Methods: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. Results: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of

Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

Triple-negative breast cancer (TNBC) is one of the major clinical problems to be solved urgently, because of its high malignancy, poor targeted therapy effect and easy occurrence of drug resistance and metastasis. Here, methyltransferase DNMT1 was identified as a key factor mediating PTX resistance for TNBC. Decitabine (DEC), an inhibitor of DNMT1, can inhibit the proliferation and metastasis of TNBC cells and reverse PTX resistance. In this study, we reported a new delivery system (DEC/PTX NPs@αPD-L1) co-loaded with DEC and PTX modified by anti-PD-L1 monoclonal antibody (αPD-L1), which can overcome drug resistance and metastasis through multi-mode synergistic effect. αPD-L1 increases the enrichment of nanoparticles in tumor tissue through active targeting effect, and blocks PD-L1 on the surface of TNBC cells, thereby activating anti-tumor immune while enhancing internalization of nanoparticles by tumor cells. Inside tumor cells, DEC inhibits EMT process and cancer stem cells to overcome PTX resistance and metastasis. PTX can not only exerts direct tumor killing effect, but also inhibit Treg cells from remodeling immune microenvironment, and induces efficient immunogenic death in cooperation with DEC. This delivery system, realizing tumor-specific synchronized chemoimmunotherapy, represents a promising therapeutic platform for TNBC.

ABSTRACT Fusarium sacchari is one of the primary pathogens causing pokkah boeng disease in sugarcane in China. Common fungal extracellular membrane (CFEM) domain-containing proteins only exist in fungi and play a significant role in the interaction of pathogens and plants. However, the CFEM proteins in F. sacchari were not identified and functionally resolved. Of the 20 FsCFEM proteins identified from the genome of F. sacchari, 16 FsCFEM genes were cloned, while 4 FsCFEM proteins (Fs06761, Fs08184, Fs10706, and Fs13617) were identified as effector proteins that could suppress the programmed cell death triggered by BCL2-associated X protein in Nicotiana benthamiana. Subcellular localization analysis revealed that these four effectors could enter plant cells and are mainly located in the cell membrane and nucleus. By the yeast YTK12 secretion system, the signal peptides of four CFEM proteins were functionally verified. The expression levels of these four effector proteins were significantly increased in the F. sacchari-infected sugarcane plants. Through fungal gene knockout, three genes (Fs06761, Fs08184, and Fs13617) were found to be important pathogenic factors for pathogens. Our results support that the FsCFEM effector proteins were virulence effectors and might be involved in regulating plant immunity. IMPORTANCE Common fungal extracellular membrane (CFEM) domain-containing protein has long been considered an essential effector, playing a crucial role in the interaction of pathogens and plant. Strategies aimed at understanding the pathogenicity mechanism of F. sacchari are eagerly anticipated to ultimately end the spread of pokkah boeng disease. Twenty FsCFEM proteins in the genome of F. sacchari have been identified, and four FsCFEM effector proteins have been found to suppress BCL2-associated X protein-triggered programmed cell death in N. benthamiana. These four effector proteins have the ability to enter plant cells and inhibit plant immunity. Furthermore, the expression of these four FsCFEM effector proteins significantly increases during the infection stage, with the three of them playing an essential role in achieving full virulence. These study findings provide a direction toward further exploration of the immune response in sugarcane. By applying these discoveries, we can potentially control the spread of disease through techniques such as host-induced gene silencing.

Abstract Background Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG. Results In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3+CD8+ murine T cells. Conclusion Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine.

3He is a splendid neutron detection material due to its high neutron reaction cross section, gaseous state, and nonelectronegative and nonpoisonous nature. With the worldwide problem of the “3He supply crisis” arising, boron-lined gaseous neutron detectors are being widely used in neutron detection to replace 3He neutron detectors. In this work, to reduce the scattering neutron background coming from the substrate of a boron-lined neutron detector in the application of neutron scattering, a new design of the boron-lined gaseous neutron detector composed of a boron-lined multichip converter and a multiwire proportional chamber was proposed. The electron drift efficiency matrix simulated by Garfield++ (Version 2023.4) and the values and positions of electron energy deposition simulated by Geant4 were obtained. The α, 7Li, and total charged particle energy deposition spectra were acquired via coupling calculations of the electron drift efficiency matrix and the values and positions of electron energy deposition, and the width of the slit was selected as 3 mm. The boron-lined multilayer converter neutron detector (BMCND) was tested using a 241Am–239Pu mixture α source, and the total count rate of α charged particles was measured as 599.5 s−1, which is 89% of the theoretical α particle emission rate of 672.9 s−1. The drift voltage experiments showed that 1200 V is enough to acquire a relatively ideal count, and a 2500 V drift voltage was confirmed, considering the higher count and instrument safety. We also performed the neutron detection experiments using a photo-neutron source, and a characteristic spectrum shape of “two stairs” was measured. When borated polyethylene was used to shield the BMCND, the detected total count decreased while keeping the characteristic spectrum shape, demonstrating that the BMCND was equipped with the ability to detect neurons, indicating that BMCNDs have the potential to be an outstanding 3He alternative neutron detector.

Abstract Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

ABSTRACT Fusarium sacchari is one of the primary pathogens causing Pokkah Boeng disease (PBD) in sugarcane in China. Pectate lyases (PL), which play a critical role in pectin degradation and fungal virulence, have been extensively studied in major bacterial and fungal pathogens of a wide range of plant species. However, only a few PLs have been functionally investigated. In this study, we analyzed the function of the pectate lyase gene, FsPL, from F. sacchari. FsPL is a key virulence factor of F. sacchari and can induce plant cell death. FsPL also triggers the pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) response in Nicotiana benthamiana, as reflected by increases in reactive oxygen species (ROS) production, electrolyte leakage, and callose accumulation, as well as the upregulation of defense response genes. In addition, our study also found that the signal peptide of FsPL was necessary for induced cell death and PTI responses. Virus-induced gene silencing showed that FsPL-induced cell death in Nicotiana benthamiana was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1. Thus, FsPL may not only be a critical virulence factor for F. sacchari but may also induce plant defense responses. These findings provide new insights into the functions of pectate lyase in host-pathogen interactions. IMPORTANCE Pokkah Boeng disease (PBD) is one of the main diseases affecting sugarcane in China, seriously damaging sugarcane production and economic development. Therefore, it is important to clarify the pathogenic mechanisms of this disease and to provide a theoretical basis for the breeding of PBD-resistant sugarcane strains. The present study aimed to analyze the function of FsPL, a recently identified pectate lyase gene from F. sacchari. FsPL is a key virulence factor of F. sacchari that induces plant cell death. Our results provide new insights into the function of pectate lyase in host-pathogen interactions.

To improve the accuracy of gear fault diagnosis and overcome the low diagnostic accuracy of the model caused by manual parameter selection, a combined diagnostic model based on time-frequency fusion features is combined with the improved global search whale optimization algorithm (GSWOA) to optimize the fault diagnosis capability of the kernel extreme learning machine (KELM). First, the time-domain and frequency-domain features of the gear fault state are extracted separately, and feature vectors are constructed through feature fusion, which overcomes the limitations of single features. Second, the GSWOA based on three strategies is used to optimize the regularization coefficient C and kernel function parameter γ of KELM, and a GSWOA-KELM fault diagnosis model is built to avoid the problem of low fault diagnosis accuracy caused by the manual selection of KELM parameters. Finally, the public dataset from Southeast University is taken to verify the performance of the proposed model by comparing it with KELM, SSA-KELM, and WOA-KELM models. The experimental results demonstrate that the improved time-frequency fusion features-based GSWOA-KELM model shows faster convergence speed and stronger global search ability. Compared with KELM, SSA-KELM, and WOA-KELM models, the performance of the proposed model has been improved by 11.33%, 8.67%, and 1.33%, respectively.

Abstract Lung cancer has been one of the leading causes of cancer-related death worldwide, and non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer morbidity, yet the pathogenesis of NSCLC has not been fully elucidated. Recently, long-chain non-coding RNA (lncRNA) has attracted widespread attention. LncRNA is a type of non-coding RNA whose transcript length exceeds 200 nucleotides. After constant research, academics updated their understanding of lncRNA, especially its role in the biological processes of cancer cells, including epigenetic regulation, cell proliferation, and cell differentiation. Notably, examination of lncRNAs could serve as potential hallmarks for clinicopathological features, long-term prognosis, and drug sensitivity. Therefore, it is necessary to explore the functions of lncRNA in NSCLC and innovate potential strategies against NSCLC based on lncRNA-related research. Herein, we reviewed the functions of lncRNA in the occurrence, diagnosis, treatment, and prognosis of NSCLC, which not only help promote a comprehensive view of lncRNA in NSCLC, but also shed light on the potential of lncRNA-based diagnosis and treatment of NSCLC.

Abstract Background Against the background of an aging population, older adults living alone in cities are increasingly dependent. However, their use of home and community-based services in China is unsatisfactory. This study attempted to figure out why older adults living alone in cities do not actively seek assistance in China. Methods In-depth interviews were conducted. A total of 29 older adults were recruited. Content analysis was used to analyze the interview data. Results Three themes were identified. (1) Desire for independence, despite hardship: The lives of older adults involve many inconveniences, but they preferred to solve problems by themselves, instead of asking for help; (2) Desire to not overburden jiaren (meaning family in Chinese): older adults did not want to disturb families or burden children with caring responsibilities. Moreover, previous experience of failing to obtain care made them reluctant to seek help from jiaren; (3) Desire to not bother wairen (meaning people other than family in Chinese): The lack of trust caused by being unfamiliar with wairen, and the fear of being a burden to others if they were not able to reciprocate, made older adults reluctant to seek help from wairen. Conclusions Changes in social, economic, and demographic structures have led to gradual failure of family care. Older adults accustomed to an “acquaintance society” have not yet adapted to seeking help from the community. When addressing the problem of care for older adults living alone in cities, it is important to focus on the profound impact of social change.

Abstract. Background:. The CHA2DS2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA2DS2–VASc score in stroke and all-cause mortality. Methods:. Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA2DS2–VASc score model. Results:. Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA2DS2–VASc score significantly improved the discrimination and reclassification power of the CHA2DS2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA2DS2–VASc model for predicting all-cause mortality. Conclusions:. Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA2DS2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

BackgroundAryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) belongs to the b HLH- PAS domain transcription factor family and is one of the key clock genes that control the circadian rhythm. ARNTL2 plays an important role in human biological functions. However, its role in various tumors, especially in the tumor immune microenvironment (TIME) and immunotherapy, remains unclear.MethodsWe integrated data from cancer patients from multiple databases, including the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI, with data from a large clinical study, three immunotherapy cohorts, and in vitro experiments to investigate the involvement of ARNTL2 expression in cancer prognosis and immune response.ResultsARNTL2 displayed abnormal expression within most malignant tumors, and is significantly associated with poorer survival and pathologic staging. Through gene-set enrichment analysis (GSEA) and gene-set variation analysis (GSVA), we found that ARNTL2 not only regulates cell cycle-related functions to promote cell proliferation but also regulates autoimmunity-related functions of the innate and adaptive immune systems, and other immune-related signaling pathways. In addition, ARNTL2 overexpression contributes to an immunosuppressive tumor microenvironment that plays a key role in immunosuppression-related features, such as the expression of immunosuppression-related genes and pathways and the number of immunosuppressive-infiltrating cells, including regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). The group of patients with low ARNTL2 expression who received immune checkpoint inhibitors (ICI) therapy had better response rates and longer survival when compared to those with high ARNTL2 expression.ConclusionThe findings of this study suggest that ARNTL2 is a potential human oncogene that plays an important role in tumorigenesis and cancer immunity. Elevated ARNTL2 expression indicates an immunosuppressive tumor microenvironment. Targeting ARNTL2 in combination with ICI therapy could bring more significant therapeutic benefits to patients with cancer. Our study sheds light on the remarkable potential of ARNTL2 in tumor immunity and provides a novel perspective for anti-tumor strategies.

Metaverse has rekindled human beings’ desire to further break space-time barriers by fusing the virtual and real worlds. However, security and privacy threats hinder us from building a utopia. A metaverse embraces various techniques, while at the same time inheriting their pitfalls and thus exposing large attack surfaces. Blockchain, proposed in 2008, was regarded as a key building block of metaverses. it enables transparent and trusted computing environments using tamper-resistant decentralized ledgers. Currently, blockchain supports Decentralized Finance (DeFi) and Non-fungible Tokens (NFT) for metaverses. However, the power of a blockchain has not been sufficiently exploited. In this article, we propose a novel trustless architecture of blockchain-enabled metaverse, aiming to provide efficient resource integration and allocation by consolidating hardware and software components. To realize our design objectives, we provide an On-Demand Trusted Computing Environment (OTCE) technique based on local trust evaluation. Specifically, the architecture adopts a hypergraph to represent a metaverse, in which each hyperedge links a group of users with certain relationship. Then the trust level of each user group can be evaluated based on graph analytics techniques. Based on the trust value, each group can determine its security plan on demand, free from interference by irrelevant nodes. Besides, OTCEs enable large-scale and flexible application environments (sandboxes) while preserving a strong security guarantee.

BackgroundCuproptosis is a novel form of programmed cell death that disrupts the tricarboxylic acid (TCA) cycle and mitochondrial function. The mechanism of cuproptosis is quite different from that of common forms of cell death such as apoptosis, pyroptosis, necroptosis, and ferroptosis. However, the potential connection between cuproptosis and tumor immunity, especially in lung adenocarcinoma (LUAD), is poorly understood.MethodsWe used machine learning algorithms to develop a cuproptosis-related scoring system. The immunological features of the scoring system were investigated by exploring its association with clinical outcomes, immune checkpoint expression, and prospective immunotherapy response in LUAD patients. The system predicted the sensitivity to chemotherapeutic agents. Unsupervised consensus clustering was performed to precisely identify the different cuproptosis-based molecular subtypes and to explore the underlying tumor immunity.ResultsWe determined the aberrant expression and prognostic relevance of cuproptosis-related genes (CRGs) in LUAD. There were significant differences in survival, biological function, and immune infiltration among the cuproptosis subtypes. In addition, the constructed cuproptosis scoring system could predict clinical outcomes, tumor microenvironment, and efficacy of targeted drugs and immunotherapy in patients with LUAD. After validating with large-scale data, we propose that combining the cuproptosis score and immune checkpoint blockade (ICB) therapy can significantly enhance the efficacy of immunotherapy and guide targeted drug application in patients with LUAD.ConclusionThe Cuproptosis score is a promising biomarker with high accuracy and specificity for determining LUAD prognosis, molecular subtypes, immune cell infiltration, and treatment options for immunotherapy and targeted therapies for patients with LUAD. It provides novel insights to guide personalized treatment strategies for patients with LUAD.

Abstract Background Cyclic GMP-AMP synthase (cGAS) is a crucial DNA sensor and plays an important role in host antiviral innate immune responses. During hepatitis B virus (HBV) infection, the cGAS signaling pathway can suppress HBV replication. As an important regulatory protein of HBV, hepatitis B virus X protein (HBx) may serve as an antagonistic character to the cGAS/STING signaling pathway. In this study, we aim to investigate the functional role of HBx in the cGAS/STING signaling pathway. Methods The effects of HBx on IFN-β promoter activity were measured by Dual-luciferase reporter assays. Ubiquitination and autophagy were analyzed by Western-blot and Co-immunoprecipitation assays. Results Our results show that HBx down-regulates IFN-I production by directly promoting ubiquitination and autophagy degradation of cGAS. Conclusions HBV can antagonize host cGAS DNA sensing to promote HBV replication and provide novel insights to develop novel approaches against HBV infection.

Abstract Background The increased number of older adults living alone has created a substantial care need. However, the utilization rate of services and facilities to meet these needs are surprisingly low. Many of older adults experience difficulties accessing these services, although it remains unclear how these obstacles impede access to services. This study explored the obstacles and difficulties experienced by urban older adults in seeking community care. Methods A phenomenological study was carried out and participatory observation and in-depth interviews were employed to investigate the process of seeking care of older adults in urban communities. A total of 18 urban community-dwelling older adults aged 75 years and over were included. Data collected were analysed by content analysis. Results We identified the pathways by which senior-only households sought community care and encountered obstacles. (1) lack of community care information: older adults did not know where and how to get services, even though the care institutions scattered throughout the community; (2) limited mobility: older adults often suffered from various chronic diseases, which physically hindered their access to care resources; (3) complex process of achieving care: the functional fragmentation and geographical dispersion of care institutions made the care-seeking process challenging and confusing for older adults; (4) incomprehension of needs expression: limited interaction time and communication barriers between staff of institutions and the older adults were the final obstacle. Only by surmounting these obstacles one by one can older adults access the care resources effectively. Conclusions When older adults in the community initiated calls for help, they encountered several obstacles. Their physiological and social disadvantages limited their ability to seek care physically. Lack of integration and clear guidance in the process of providing community care exacerbated these difficulties. Reform of care services should focus on the visibility and accessibility of services for older adults.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1β. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Background:A. chinense frequently used in Miao medicine to treat rheumatic diseases. However, as a famous toxic herb, Alangium chinense and its representative components exhibit ineluctable neurotoxicity, thus creating significant challenges for clinical application. The combined application with compatible herbs in Jin-Gu-Lian formula attenuates such neurotoxicity according to the compatible principle of traditional Chinese medicines.Purpose: We aimed to investigate the detoxification of the compatible herbs in Jin-Gu-Lian formula on A. chinense-induced neurotoxicity and investigate its mechanism.Methods: Neurobehavioral and pathohistological analysis were used to determine the neurotoxicity in rats administered with A. chinense extract (AC), extract of compatible herbs in Jin-Gu-Lian formula (CH) and combination of AC with CH for 14 days. The mechanism underlying the reduction of toxicity by combination with CH was assessed by enzyme-linked immunosorbent assays, spectrophotometric assays, liquid chromatography tandem-mass spectrometry and real-time reverse transcription-quantitative polymerase chain reaction.Results: Compatible herbs attenuated the AC-induced neurotoxicity as evidenced by increased locomotor activity, enhanced grip strength, the decreased frequency of AC-induced morphological damage in neurons, as well as a reduction of neuron-specific enolase (NSE) and neurofilament light chain (NEFL) levels. The combination of AC and CH ameliorated AC-induced oxidative damage by modulating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). AC treatment significantly reduced the levels of monoamine and acetylcholine neurotransmitters in the brains of rats, including acetylcholine (Ach), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), and serotonin (5-HT). Combined AC and CH treatment regulated the abnormal concentrations and metabolisms of neurotransmitters. Pharmacokinetic studies showed that the co-administration of AC and CH significantly decreased plasma exposure levels of two main components of AC, as evidenced by the reduction of maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) compared to AC. In addition, the AC-induced downregulation in mRNA expression of cytochrome P450 enzymes was significantly reduced in response to combined AC and CH treatment.Conclusion: Compatible herbs in Jin-Gu-Lian formula alleviated the neurotoxicity induced by A. chinense by ameliorating oxidative damage, preventing abnormality of neurotransmitters and modulating pharmacokinetics.