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Wildfires exert strong influences on the environment, ecology, economy and public security. However, the existing hourly Himawari-8 fire product produced by the Japan Meteorological Agency (JMA) presents large uncertainties and is not suitable for reliable real-time fire monitoring in China. To fill this gap, the National Satellite Meteorological Center (NSMC) proposed an adaptive hourly Himawari-8 fire product for China based on the original Himawari-8 source by employing a dynamical threshold for fire extraction and a database of ground thermal sources. According to the visually extracted reference and consistency check, we found that the NSMC-Himawari-8 fire product effectively removed a majority of false fire alarms included in the original Himawari-8 fire product. Based on a rare field-collected ground reference dataset, we evaluated the reliability of original Himawari-8 and NSMC-Himawari-8 fire products across China. The overall accuracy of the raw Himawari-8 fire product was 54 % and 59 % (not considering the omission errors), respectively. As a comparison, by identifying more real fire pixels and avoiding a majority of false fire alarms, the overall accuracy of the NSMC-Himawari-8 fire product was 80 % and 84 % (not considering the omission errors), respectively, making it an ideal source for improved real-time fire monitoring across China. This research also provides a useful reference for employing a local dataset of underlying surfaces and thermal sources to enhance the accuracy of global fire products in specific regions. The NSMC-Himawari-8 fire product can be downloaded at http://figshare.com (last access: 17 April 2023) with the following DOI: https://doi.org/10.6084/m9.figshare.21550248 (Chen et al., 2022a).

This paper considers distributed stochastic optimization, in which a number of agents cooperate to optimize a global objective function through local computations and information exchanges with neighbors over a network. Stochastic optimization problems are usually tackled by variants of projected stochastic gradient descent. However, projecting a point onto a feasible set is often expensive. The Frank-Wolfe (FW) method has well-documented merits in handling convex constraints, but existing stochastic FW algorithms are basically developed for centralized settings. In this context, the present work puts forth a distributed stochastic Frank-Wolfe solver, by judiciously combining Nesterov's momentum and gradient tracking techniques for stochastic convex and nonconvex optimization over networks. It is shown that the convergence rate of the proposed algorithm is $\mathcal{O}(k^{-\frac{1}{2}})$ for convex optimization, and $\mathcal{O}(1/\mathrm{log}_2(k))$ for nonconvex optimization. The efficacy of the algorithm is demonstrated by numerical simulations against a number of competing alternatives., Comment: 15 pages, 11 figures, 2 tables

The rapid recombination of carriers on plasmon metal nanoparticles leads to relatively low efficiency of traditional photocatalysts. The combination of a metal and a semiconductor allows to the separation of hot electrons and holes to improve photocatalytic efficiency. In this study, Au nanoparticles were integrated with semiconductor TiO2 nanoparticles of different sizes to improve the photocatalytic activity. Various techniques have been developed to study the mechanism of catalytic activity, the significance of band bending in the space-charge region within metal–semiconductor nanocomposites, and the built-in electric field. The results provide theoretical and experimental evidence for the design of a high-performance surface plasmon resonance (SPR) photocatalyst. To reveal the interface band structure, surface-enhanced Raman spectroscopy (SERS) was employed to analyze the band structure of the TiO2–metal composites. This approach was based on the electrochemical Stark effect and a molecular probe strategy, combined with X-ray photoelectron spectroscopy (XPS), Electrochemical impedance spectroscopy (EIS), and other techniques at the molecular level. The results demonstrated that charge transfer occurred spontaneously between the Au nanoparticles and TiO2, and that the TiO2–metal interface constitutes a Schottky barrier. Moreover, the size of the TiO2 nanoparticles affects the degree of band bending. Optimal state matching was achieved with TiO2 (60 nm)–Au, improving the photocatalytic activity of the nanocomposite. The photocatalytic coupling reaction of p-aminothiophenol (PATP) acted as a probe to study the catalytic performance of TiO2–metal nanocomposites. The results revealed that the introduction of TiO2 improves the SPR catalytic activity of Au, mainly through the efficient separation of electrons and holes at the TiO2–metal interface.

Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.

Biliary tract cancers (BTCs) comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses. The benefit of chemotherapy seems to have reached a bottleneck and, therefore, new effective therapeutic strategies for advanced BTCs are needed. Molecularly targeted therapies in selected patients are rapidly changing the situation. However, the low frequency of specific driver alterations in BTCs limits their wide application. Recently, immunotherapeutic approaches are also under active investigation in BTCs, but the role of immunotherapy in BTCs remains controversial.PubMed, Web of Science, and meeting resources were searched for relevant articles published from January 2017 to May 2022. The search aimed to identify current and emerging immunotherapeutic approaches for BTCs. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/.Immunotherapy in BTC patients is currently under investigation, and most of the investigations focused on the application of immune checkpoint inhibitors (ICIs). However, only a subgroup of BTCs with microsatellite-instability high (MSI-H)/DNA mismatch repair-deficient (dMMR) or tumor mutational burden-high (TMB-H) benefit from monotherapy of ICIs, and limited activity was observed in the second or subsequent settings. Nevertheless, promising results come from studies of ICIs in combination with other therapeutic approaches, including chemotherapy, in advanced BTCs, with a moderate toxicity profile. Recent studies demonstrated that compared to GEMCIS alone, durvalumab plus GEMCIS significantly improved patient survival (TOPAZ-1 trial) and that ICIs-combined chemoimmunotherapy is poised to become a new frontline therapy option, regardless of TMB and MMR/MSI status. Adoptive cell therapy and peptide- or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs. Numerous biomarkers have been investigated to define their predictive role in response to ICIs, but no predictive biomarker has been validated, except MSI-H/dMMR.The role of immunotherapy in BTCs is currently under investigation and the results of ongoing studies are eagerly anticipated. Several studies have demonstrated the safety and efficacy of ICIs in combination with chemotherapy in treatment-naive patients, such as the phase III TOPAZ-1 trial, which will change the standard care of first-line chemotherapy for advanced BTCs. However, further research is needed to understand the best combination with immunotherapy and to discover more predictive biomarkers to guide clinical practice.

Hanbi Wang,1 Zhiyuan Zhang,2 Jie Chen,1 Han Dong,3 Ying Zou,4 Wei Wang,5 Qingmei Zheng,6 Ying Feng,7 Zhangyun Tan,8 Xiaoqin Zeng,9 Yinqing Zhao,8 Yanfang Wang,1 Aijun Sun1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of International Medical Service, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, People’s Republic of China; 4Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 8Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, People’s Republic of China; 9Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnObjective: To explore the needs of obstetricians and gynecologists with different working years for the contents and forms of CME.Methods: The online questionnaire was distributed on the largest academic training platform for obstetrics and gynecology in China from April 2020 to May 2020. The survey contents mainly included the training forms and training contents of CME, as well as the mastery of diseases by doctors with different working years.Results: 4458 questionnaires were returned, of which 3954 questionnaires were included in the study. There was a significant (p < 0.001) positive correlation between the mastery of 19 diseases by obstetricians and gynecologists with different working years. After adjusting for specialist departments, hospital grades, nature of units and ages, it was found that there was no statistically significant difference between the groups in gynecological endocrine-related diseases, such as precocious puberty/delayed puberty, and there was also no statistically significant difference between the groups of shorter working years in infertility, menopausal syndrome, hyperprolactinemia and premature ovarian failure.Conclusion: The most popular training content for obstetricians and gynecologists with different working years is common gynecological endocrine diseases, of which abnormal uterine bleeding, menopausal syndrome, polycystic ovarian syndrome and cervical lesions are the most selected diseases, and the most popular form of training is online.Keywords: continuing medical education, working years, internet, obstetrics and gynecology

Peer reviewed: True, Acknowledgements: We want to thank the Lee Lab, the FinnGen study, the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), and the Genetic Epidemiology Research on Aging (GERA) for sharing data. XL: the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001). XYW: National Natural Science Foundation of China (81970494) and Key Project of Research and Development Plan of Hunan Province(2019SK2041); SCL: the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019–00977), and the Swedish Cancer Society (Cancerfonden). Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication., Funder: Cancerfonden; FundRef: http://dx.doi.org/10.13039/501100002794, BACKGROUND: Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases. METHODS: Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption. RESULTS: Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation. CONCLUSIONS: This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases. FUNDING: The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.

Under the background of the era of big data, the physical education teaching evaluation system of colleges and universities has more characteristics and manifestations of the new era. At the same time, big data also brings more requirements for the improvement of the physical education teaching evaluation system of colleges and universities. Under such an environment and trend, colleges and universities need to make certain reform measures to meet the challenges calmly according to the requirements of the new era. This paper makes a systematic study on the construction of the evaluation system of physical education teaching in colleges and universities, expounds the theoretical basis of building an efficient evaluation system of physical education teaching, analyzes the components of the evaluation system, and gives the construction path of the evaluation system of physical education teaching in colleges and universities. The purpose of this paper is to provide some reference information for physical education in higher education and the cultivation of talents' comprehensive quality.

To identify bioactive metabolites from the fruiting body of Morchella sextelata, fourteen metabolites (1–14) including one undescribed morchesexten A (1) were isolated. Their structures including absolute configurations were assigned on the basis of spectroscopic data and quantum chemical computational methods. Furthermore, the anti-inflammatory and antioxidant activities of the isolated compounds were evaluated. Compounds 10–12 showed inhibitory effects on nitric oxide (NO) production with IC50 values of 15.2 ± 2.7, 10.2 ± 1.9 and 35.3 ± 10.5 μM, respectively. Compounds 7 and 9 exhibited strong antioxidant effect with IC50 values of 6.7 ± 0.4 and 7.3 ± 0.8 μM compared with Vit C (IC50 15.4 ± 0.2 μM).

Wireless sensor networks are widely used in the field of monitoring. For data collection of sensor nodes in large-scale monitoring scenarios, UAV-assisted wireless sensor networks have emerged. For the security and validity of data collection, a blockchain-enhanced data collection framework for UAV-assisted wireless sensor networks is presented in this work. To reduce data redundancy in wireless sensor networks, a sparsity-optimized and compressed sensing-based spatiotemporal data aggregation model is built. A UAV identity authentication mechanism based on a Merkle tree is also designed to ensure the security of data transmission. By combining blockchain building and data aggregation, a disaster semantic blockchain based on a data reconstruction-directed consensus mechanism is presented. Disaster semantics are extracted by analyzing the semantic association relationship of disaster, background, event, and sensor data. The experimental results show that the blockchain-enhanced spatiotemporal data aggregation effectively increases the network life cycle and data reconstruction accuracy. The disaster situation can be described accurately through the disaster semantic blockchain.

BackgroundRecent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear.MethodsThe present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10−5) and the genome-wide statistical significance threshold (5 × 10−8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran’s Q test, and leave-one-out test, were carried out to assess the robustness of our findings.ResultsOur study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy.ConclusionThis study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.

Multiagent dynamic task assignment of forest fires is a complicated optimization problem because it requires the consideration of multiple factors, such as the spread speed of fires, firefighting speed of agents, the movement speed of agents, and the number of deployed agents. In this article, we investigate multiagent dynamic task assignment based on a forest fire point model, the objective of which is to minimize task completion time. First, we establish a model for the spread of fire and dynamic task assignments. Second, we prove that the optimal static task assignment always makes all task completion times the same under certain assumptions. Furthermore, we calculate the optimal solution to the static task assignment problem assuming no travel time for the agents, which provides the theoretical basis for the initial deployment and dynamic deployment. Third, we propose a dynamic task assignment scheme based on the global information, which ensures that every reassignment reduces the task completion time and makes all task completion times close to each other. Finally, the simulation is carried out on the MATLAB platform to verify the performance of the proposed dynamic task assignment scheme by comparing with a multistage global auction algorithm. We hope that this work provides insight for decision-makers designing reasonable assignment strategies based on the model and solving assignment optimization problem in different situations.

The peroxisome proliferator-activated receptor gamma (PPARγ) are nuclear receptors with distinct roles in energy metabolism and immunity. Although extensively studied in mammals, immunomodulatory roles of this molecule in teleost fish remain to be investigated. In this study, large yellow croaker (Larimichthys crocea) PPARγ (LcPPARγ) sequence was cloned, which encodes a polypeptide of 541 amino acids that include signature domains belonging to the nuclear receptor superfamily. Phylogenetically, LcPPARγ was most closely related to PPARγ derived from European sea bass (Dicentrarchus labrax). Quantitative analysis shown a ubiquitous expression of this molecule, with highest expression level detected in the intestine. The expression of LcPPARγ was decreased in the intestine, muscle, body kidney, spleen and head kidney-derived monocytes/macrophages (MO/MФs) over the course of Vibrio alginolyticus (V. alginolyticus) infection. In contrast, an up-regulation of LcPPARγ was observed in head kidney-derived MO/MФs following docosahexaenoic acid (DHA) treatment. This increase in LcPPARγ leads to an up-regulation of LcCD11b and LcCD18 and an enhancement of complement-mediated phagocytosis. Furthermore, cytokine secretions of V. alginolyticus-stimulated MO/MФs were modulated following LcPPARγ activations that up-regulated the expression of LcIL-10, while decreased the expression of LcIL-1β, LcTNF-α and LcTGF-β1. Overall, our results indicated that LcPPARγ plays a role in regulating functions of MO/MФs and likely contribute to MO/MФs polarization.

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2(+)) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST(+)), but not protein kinase C-δ-expressing (PKC-δ(+)), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2(+) neurons. The SST(+) neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST(+) GABAergic neurons, but not PKC-δ(+) GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeA(SST)–DpMe(VGLUT2) circuit that regulates licking behavior and promotes water intake. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-021-00817-2.

This research aimed to study the inhibitory effect of Glurenorm (gliquidone) on epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells based on the diabetic nephropathy (DN) model. In this study, 30 specific pathogen-free (SPF) mice were selected to construct DN model and randomly rolled into groups A, B, and C, with 10 mice in each group. Low-dose, mediumdose, and high-dose Glurenorm were administered intragastrically. The results showed that the serum urea nitrogen content (7.23±0.39 mmol/L, 6.18±0.46 mmol/L) of control and C group was considerably inferior to A group (8.01±0.48 mmol/L), and the content of C group was greatly lower than controls (P < 0.05). The creatinine clearance rate (2.97±0.44 mL/min, 4.02±0.31 mL/min) of mice in control and C group was notably superior to A group (2.18±0.38 mL/min), and that of C group was obviously higher versus controls (P < 0.05). After 5 weeks of intragastric intervention by Glurenorm, the body mass of the mice in control and C group was evidently lower relative to A group, and that of C group was obviously higher versus controls (P < 0.05). Mice in control and C group were remarkably lower in body mass at the 7th week after Glurenorm intervention versus A group, and C group was relatively lower versus controls (P < 0.05). In short, EMT played an important role in promoting the occurrence and progression of renal fibrosis. Glurenorm can reduce the progression of renal fibrosis, inhibit EMT of renal tubular epithelial cells, and effectively protect kidney function.

BACKGROUND: The anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC. METHODS: In this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA–IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m(2) once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles. RESULTS: Between May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively. CONCLUSIONS: In women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

Understanding how plant pathogenic fungi adapt to their hosts is of critical importance to securing optimal crop productivity. In response to pathogenic attack, plants produce reactive oxygen species (ROS) as part of a multipronged defense response. Pathogens, in turn, have evolved ROS scavenging mechanisms to undermine host defense. Thioredoxins (Trx) are highly conserved oxidoreductase enzymes with a dithiol-disulfide active site, and function as antioxidants to protect cells against free radicals, such as ROS. However, the roles of thioredoxins in Verticillium dahliae, an important vascular pathogen, are not clear. Through proteomics analyses, we identified a putative thioredoxin (VdTrx1) lacking a signal peptide. VdTrx1 was present in the exoproteome of V. dahliae cultured in the presence of host tissues, a finding that suggested that it plays a role in host-pathogen interactions. We constructed a VdTrx1 deletion mutant ΔVdTrx1 that exhibited significantly higher sensitivity to ROS stress, H2O2, and tert-butyl hydroperoxide (t-BOOH). In vivo assays by live-cell imaging and in vitro assays by western blotting revealed that while VdTrx1 lacking the signal peptide can be localized within V. dahliae cells, VdTrx1 can also be secreted unconventionally depending on VdVps36, a member of the ESCRT-II protein complex. The ΔVdTrx1 strain was unable to scavenge host-generated extracellular ROS fully during host invasion. Deletion of VdTrx1 resulted in higher intracellular ROS levels of V. dahliae mycelium, displayed impaired conidial production, and showed significantly reduced virulence on Gossypium hirsutum, and model plants, Arabidopsis thaliana and Nicotiana benthamiana. Thus, we conclude that VdTrx1 acts as a virulence factor in V. dahliae.

Background Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. Methods Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. Results During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10–5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted 3 for PM2.5 and NO2, –5/m BC and 3 association was inverse for all outcomes. Including noise attenuated all outcome associations, though many remained significant. Across outcomes, noise was robust to adjustment to air pollutants (e.g. natural mortality 1.037 (1.033, 1.042) per 10 dB Lden total transportation noise, after including BC). Conclusion Long-term exposure to air pollution and transportation noise in Switzerland contribute to premature mortality. Considering co-exposures revealed the importance of local traffic-related pollutants such as NO2, BC and transportation noise.

Background We aimed to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. Methods We collected nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients. The enrolled patients were randomly divided into training and validation cohorts. Lasso regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration and clinical effectiveness of the model. Results A total of 2,020 patients were included. The median OS was 56.50 months (95% CI, 50.36–62.65 months). In the training cohort of 1,425 patients, through Lasso regression cross-validation, thirteen characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5- and 10-year OS were 0.848, 0.826, 0.814 and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723–8.397; log-rank P P

Acquired brain injury (ABI) is the most common disease of the nervous system, involving complex pathological processes, which often leads to a series of nervous system disorders. The structural destruction and dysfunction of the Neurovascular Unit (NVU) are prominent features of ABI. Therefore, understanding the molecular mechanism underlying NVU destruction and its reconstruction is the key to the treatment of ABI. SUMOylation is a protein post-translational modification (PTM), which can degrade and stabilize the substrate dynamically, thus playing an important role in regulating protein expression and biological signal transduction. Understanding the regulatory mechanism of SUMOylation can clarify the molecular mechanism of the occurrence and development of neurovascular dysfunction after ABI and is expected to provide a theoretical basis for the development of potential treatment strategies. This article reviews the role of SUMOylation in vascular events related to ABI, including NVU dysfunction and vascular remodeling, and puts forward therapeutic prospects.

Background To understand the shared genetic basis between colorectal cancer (CRC) and other cancers and identify potential pleiotropic loci for compensating the missing genetic heritability of CRC. Methods We conducted a systematic genome-wide pleiotropy scan to appraise associations between cancer-related genetic variants and CRC risk among European populations. Single nucleotide polymorphism (SNP)-set analysis was performed using data from the UK Biobank and the Study of Colorectal Cancer in Scotland (10 039 CRC cases and 30 277 controls) to evaluate the overlapped genetic regions for susceptibility of CRC and other cancers. The variant-level pleiotropic associations between CRC and other cancers were examined by CRC genome-wide association study meta-analysis and the pleiotropic analysis under composite null hypothesis (PLACO) pleiotropy test. Gene-based, co-expression and pathway enrichment analyses were performed to explore potential shared biological pathways. The interaction between novel genetic variants and common environmental factors was further examined for their effects on CRC. Results Genome-wide pleiotropic analysis identified three novel SNPs (rs2230469, rs9277378 and rs143190905) and three mapped genes (PIP4K2A, HLA-DPB1 and RTEL1) to be associated with CRC. These genetic variants were significant expressions quantitative trait loci in colon tissue, influencing the expression of their mapped genes. Significant interactions of PIP4K2A and HLA-DPB1 with environmental factors, including smoking and alcohol drinking, were observed. All mapped genes and their co-expressed genes were significantly enriched in pathways involved in carcinogenesis. Conclusion Our findings provide an important insight into the shared genetic basis between CRC and other cancers. We revealed several novel CRC susceptibility loci to help understand the genetic architecture of CRC.

Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic options. To explore phosphatase and tension homology deleted on chromosome ten (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second line efficacy of bortezomib in PTEN-deficient advanced ICC patients. Methods: Between July 1, 2017, and June 30, 2021, a total of 130 patients with advanced ICC were screened by PTEN immunohistochemical staining and 16 patients were enrolled. Patients with PTEN deficiency who had progressed after gemcitabine combined cisplatin received single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Results: The median time of follow up was 4.63 months (95% CI: 0.7~17.2 months). Among the 16 enrolled patients, 13 of them had completed treatment with bortezomib at least 2 cycles and been evaluated. The ORR was 23% (3/13) and disease control rate was 54% (7/13). The median progress-free survival (mPFS) was 2.95 months (95% CI: 2.1~5.1 months) and the median overall survival (mOS) was 7.2 (95% CI: 0.7~21.6 months) months in the intent-to-treat patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining score of 0 were more likely to benefit from bortezomib than those with staining score > 0. Conclusions: Bortezomib yielded encouraging objective response and a favorable overall survival as a second-line therapy in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising treatment option in selected ICC patients with PTEN deficiency. Trial Registration: ClinicalTrials.gov (NCT03345303).

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Underwater marine object detection, as one of the most fundamental techniques in the community of marine science and engineering, has been shown to exhibit tremendous potential for exploring the oceans in recent years. It has been widely applied in practical applications, such as monitoring of underwater ecosystems, exploration of natural resources, management of commercial fisheries, etc. However, due to complexity of the underwater environment, characteristics of marine objects, and limitations imposed by exploration equipment, detection performance in terms of speed, accuracy, and robustness could be degraded dramatically when conventional approaches are used. Deep learning has been found to have significant impact on a variety of applications, including marine engineering. In this context, we offer a review of deep-learning-based underwater marine object detection techniques. Underwater object detection can be performed by different sensors, such as acoustic sonar, or optical camera. In this paper, we prefer to focus on vision-based object detection due to some significant competitive advantages. To facilitate a thorough understanding of this subject, we organize research challenges of vision-based underwater object detection into Four categories, namely image quality degradation, small object detection, poor generalization, and real-time detection. We review recent advances in underwater marine object detection and highlight advantages and disadvantages of existing solutions for each challenge. In addition, we examine the most extensively used datasets in detail and critically. Comparative studies with previous reviews, notably approaches that leverage artificial intelligence, and future trends on this hot topic are also presented. * This work has been published on Sensors.

Background Cancer patients have a high incidence of malnutrition, but traditional nutritional screening tools have low sensitivity and specificity, so they cannot properly stratify patient prognosis. Thus, we aimed to identify the nutritional indexes associated with patient prognosis, construct a prognostic model, and develop a nomogram for predicting individual survival probability. Methods Based on real-world data, patients admitted to the Department of Chemotherapy & Radiotherapy in Taizhou Cancer Hospital from January 1, 2017, to July 1, 2020, were included in the analysis. We collected nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients. The enrolled patients were randomly divided into training and validation cohorts in a 7:3 ratio. Lasso regression cross-validation was used in the training cohort to determine the variables to include in the Cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration and clinical effectiveness of the model. Results A total of 2,020 patients were included. The median follow-up time was 33.48 months (IQR, [15.79, 56.73] months), and the median OS was 56.50 months (95% CI, 50.36–62.65 months). In the training cohort of 1,425 patients, through Lasso regression cross-validation, thirteen characteristics were included in the model: sex, age, baseline weight, food intake reduction grade, emerging disease, ECOG performance status, hospitalization frequency, prealbumin, albumin, clinical stage, hemoglobin suppression grade, platelet suppression grade, and liver function classification. Based on these factors, a Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5- and 10-year OS were 0.848, 0.826, 0.814 and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723–8.397; log-rank P P

The safety of geotechnical engineering in cold region depends on the stability of supporting structure. Wet shotcrete technology (WST) has the advantages of less dust on the working surface, low rebound and high strength of shotcrete layer, so it has been gradually applied in roadway support of broken surrounding rock. In the cold environment, the decrease of the curing temperature of WST will have an impact on the development of shotcrete strength, but the influence of this temperature difference has not been fully considered in the current engineering practice. Aiming at the phenomenon of small thickness, low strength, and easy cracking of shotcrete in the application of WST in a mine in alpine environment, the temperature effect study on the strength evolution of WST was carried out. The research puts forward the optimization measures for WST support in the alpine environment, which effectively improves the structural strength of the shotcrete, the support repair rate is greatly reduced, and the support efficiency is significantly improved, it also provides reference for WST construction under similar engineering conditions.

To examine the strength and mechanical characteristics of self-compacting tailings, a direct shear test was conducted under various consolidation states and moisture contents to determine the cohesion and internal friction angle of the tailings. The degree of cohesion and the internal friction angle of unsaturated tailings increased initially before declining as the moisture content rose. The maximum cohesion and internal friction angle were reached when the moisture content was around 14%. When combined with the Coulomb shear strength formula and the tailings self-weight compaction model, the expressions for the active pressure and passive pressure of tailings at any height on the lateral restraint were obtained. An improvement in cohesion and the internal friction angle of unsaturated tailings was seen with increased consolidation stress, which became stable when the consolidation stress was greater than 1 MPa. The limited equilibrium method was used to establish the three-dimensional mechanical equilibrium of the cemented body. A strength model of cementation at the open stoping stage with subsequent filling was developed after the three-dimensional strength analytical model of cementation in step 1 was modified. The difference between the design value and the measured value was 0.2 MPa. The strength of the one-step cemented backfill design, as well as the design and erection of the backfill retaining wall, was supported technically and theoretically by this study.

Tibetan Plateau (TP) is strongly impacted by accelerated anthropogenic warming that already exceeds natural variability. However, the spatial differences in climate and ecosystem response in TP between anthropogenic and natural forcings are unclear. Here, the Köppen–Trewartha climate classification is applied to examine the shifts in terrestrial climate regimes and vegetation distribution in TP by analyzing the WorldClim high-resolution downscaled climate dataset for the mid-Holocene (MH, ∼6 cal ka BP), the present-day (PD, 1960–1990), and in the future (2050s) under the Representative Concentration Pathway (RCP) 4.5 and RCP8.5 scenarios. The results show that the polar climate and the dry climate occupied more than 70% of TP area in the three periods. The MH, dominated by the natural forcing, is featured as having less distribution of dry climate than the PD. The anthropogenic change will promote a transition from a cold climate type to a warmer climate type in the 2050s. The precipitation change is responsible for the differences in climate types between the MH and PD, while warming dominates the evolution of climate types across TP in the 2050s. Moreover, vegetation types can be represented by major climate types in a large proportion of TP. In particular, polar climate regions correspond well to the areas of meadows, and the dry climate regions correspond to the steppes and deserts areas. The large changes in the climate regimes of TP suggest an extensive (shrinking) area of meadows (steppes) under natural forcing and a shrinking area of meadows under anthropogenic warming.

Yeast β-glucan is a polysaccharide purified from the Saccharomyces cerevisiae cell wall, and its multiple biological activities are essential for immune regulation. However, the effect of β-glucan on the intestinal immune response during colitis-associated colorectal cancer (CAC) is unclear. Here, we explore the possible role of β-glucan in the development of CAC. Wild type (WT) mice with CAC induced by azoxmethane (AOM) and dextran sodium sulfate (DSS) had fewer tumors than untreated mice after oral β-glucan because of increased antitumor dendritic cells (DCs) in the tumor microenvironment, resulting in more CD8+ T cells and the production of related cytokines. β-glucan also increased resistance to DSS-induced chronic colitis by reshaping the inflammatory microenvironment. These data suggest that β-glucan improves experimental intestinal inflammation and delays the development of CAC. Therefore, β-glucan is feasible for treating chronic colitis and CAC in clinical practice.