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Abstract Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein‐Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV‐ (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC‐associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene‐edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV‐coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV‐ and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

Objective and Approach Canada’s federated health data system along with access pathways geared toward academic research, pose challenges for knowledge Users (KUs) requiring timely, pan-Canadian evidence to inform decisions. To understand challenges and explore solutions, we conducted two use cases for a pan-Canadian health technology assessment organization and a federal agency, using health administrative data at one federal and six provincial data centres. The population-based cohort studies described socio-demographics, comorbidities, treatment patterns, service utilization and costs. One focused on spinal muscular atrophy, a rare disease and the other on dementia, a complex chronic disease. Results Administrative challenges included aligning varied ethical review and data access policies/procedures including requiring local and/or academic principal investigators and differing definitions of “research” vs. planning, evaluation, and monitoring. Data-related challenges included differences in structure, timeliness, and completeness across regions resulting in difficulty aligning constructs such as incident cases and episodes of care. Privacy requirements prohibited pooling jurisdictional estimates resulting in “small cells” that couldn’t be shared with KUs. Conclusions We provided analytic outputs from multiple regions, albeit with some differences and gaps, increasing knowledge around both diseases while developing capacity for combined analyses and gaining insight into national possibilities for data access. Implications As decision makers must rely on best available information, some data is better than none. However, to improve data-analytic services for Pan-Canadian KUs, next steps will include improving data harmonization, expanding data assets and filling data gaps, implementing common data models, and exploring options for federated and/or pooled analyses.

Abstract Background The aim of the present study was to compare the predictive accuracy of PD‐L1 immunohistochemistry (IHC), tissue or blood tumor mutation burden (tTMB, bTMB), gene expression profile (GEP), driver gene mutation, and combined biomarkers for immunotherapy response of advanced non‐small cell lung cancer (NSCLC). Methods In part 1, clinical trials involved with predictive biomarker exploration for immunotherapy in advanced NSCLC were included. The area under the curve (AUC) of the summary receiver operating characteristic (SROC), sensitivity, specificity, likelihood ratio and predictive value of the biomarkers were evaluated. In part 2, public datasets of immune checkpoint inhibitor (ICI)‐treated NSCLC involved with biomarkers were curated (N = 871). Odds ratio (OR) of the positive versus negative biomarker group for objective response rate (ORR) was measured. Results In part 1, the AUC of combined biomarkers (0.75) was higher than PD‐L1 (0.64), tTMB (0.64), bTMB (0.68), GEP (0.67), and driver gene mutation (0.51). Combined biomarkers also had higher specificity, positive likelihood ratio and positive predictive value than single biomarkers. In part 2, the OR of combined biomarkers of PD‐L1 plus TMB (PD‐L1 cutoff 1%, 0.14; cutoff 50% 0.13) was lower than that of PD‐L1 (cutoff 1%, 0.33; cutoff 50% 0.24), tTMB (0.28), bTMB (0.48), EGFR mutation (0.17) and KRAS mutation (0.47), for distinguishing ORR of patients after immunotherapy. Furthermore, positive PD‐L1, tTMB‐high, wild‐type EGFR, and positive PD‐L1 plus TMB were associated with prolonged progression‐free survival (PFS). Conclusion Combined biomarkers have superior predictive accuracy than single biomarkers for immunotherapy response of NSCLC. Further investigation is warranted to select optimal biomarkers for various clinical settings.

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is a distinctive member of the serine–threonine protein AGC kinase family and an effective kinase for cAMP signal transduction. In recent years, scuticociliate has caused a lot of losses in domestic fishery farming, therefore, we have carried out morphological and molecular biological studies. In this study, diseased guppies (Poecilia reticulata) were collected from an ornamental fish market, and scuticociliate Philaster apodigitiformis Miao et al., 2009 was isolated. In our prior transcriptome sequencing research, we discovered significant expression of the β-PKA gene in P. apodigitiformis during its infection process, leading us to speculate its involvement in pathogenesis. A complete sequence of the β-PKA gene was cloned, and quantified by quantitative reverse transcription-polymerase chain reaction to analyse or to evaluate the functional characteristics of the β-PKA gene. Morphological identification and phylogenetic analysis based on small subunit rRNA sequence, infection experiments and haematoxylin–eosin staining method were also carried out, in order to study the pathological characteristics and infection mechanism of scuticociliate. The present results showed that: (1) our results revealed that β-PKA is a crucial gene involved in P. apodigitiformis infection in guppies, and the findings provide valuable insights for future studies on scuticociliatosis; (2) we characterized a complete gene, β-PKA, that is generally expressed in parasitic organisms during infection stage and (3) the present study indicates that PKA plays a critical role in scuticociliate when infection occurs by controlling essential steps such as cell growth, development and regulating the activity of the sensory body structures and the irritability system.

Abstract The perception of fish locomotion is important for understanding their adaptive behaviors and ethological characteristics. However, the main strategy used for extracting fish attitudes involves the use of a vision-based monitoring system, which is limited in its range of observation and cannot perform tracking for long times. Here, we report the use of a wearable tagging electronic device, referred to as an underwater vest, to capture the surrounding flow field disturbances triggered by swimming or momentary postural changes. All of these goals were achieved by integrating a pair of pseudocapacitive pressure-sensing units and a flexible circuit board. Notably, additional conditions, such as variable hydraulic pressures and minimal changes in fish posture, require high stability and sensitivity of the sensing units. Thus, hybrid hydrogel electrodes were developed through cross-linking MXene with holey-reduced graphene oxide nanosheets and further modification with 1-ethyl-3-methylimidazolium dicyanamide ionic liquids, which increased the interfacial capacitance and long-term interfacial activity of the MXene. Consequently, the sensing unit exhibited ultrahigh sensitivity (S max~136,207 kPa−1) in an aquatic environment for 60 days and superior high-pressure resolution (10 Pa) within a wide working range of 1 MPa. Ultimately, an underwater vest integrated with such sensing units clearly distinguished and recorded fish locomotion. We believe that the designed device may open avenues in flow field monitoring and ocean current detection and provide new insights into the development of sensitive underwater tagging.

Abstract Background Nursing students require improvement in their intravenous infusion therapy management skills, yet traditional training models possess deficiencies. The Teaching for Understanding (TfU) Framework can enhance the teaching-learning process and support quality education. Therefore, utilizing TfU framework for training may promote the performance of nurses. Methods Utilizing a non-synchronized design, 102 nurses were recruited using a convenience sampling method. Fifty-one student nurses from August 2019 to January 2021 were designated as the control group, and 51 student nurses from February 2021 to July 2022 were included as the intervention group. The control group received traditional teaching methods, while the intervention group was trained based on TfU framework. The impact was gauged through medical education environment perception, theory and practice assessments, and learning satisfaction surveys. Results After the training, there was no significant difference between the control group and the intervention group in the theory assessment. However, the practice assessment scores of the intervention group were significantly higher than those of the control group. Compared with the control group, the learning satisfaction scores of the trained nurses in the intervention group were significantly higher, exhibiting significant differences, particularly in communication ability, teamwork cooperation, summing up capability, and interest in learning improvement. Furthermore, the scores of the learning perceptions, atmosphere, social self-perceptions, and total scores of the intervention group were significantly higher. Conclusion Training using TfU framework can heighten students’ understanding and command over knowledge and skills, fuel their learning fervor, and enhance their communication and collaboration abilities. TfU framework should be disseminated in medical education to improve the quality of education.

Abstract Background Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. Methods The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. Results Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. Conclusion Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

ABSTRACTThe prevalence and dissemination of the plasmid-mediated fluoroquinolone (FQ) resistance gene qnr in Salmonella are considered serious public health concerns worldwide. So far, no comprehensive large-scale studies have focused on the prevalence and genetic characteristics of the qnr gene in Salmonella isolated from chickens. Herein, this study aimed to investigate the prevalence, antimicrobial resistance (AMR) patterns, and molecular characteristics of chicken-originated qnr-positive Salmonella strains from chicken farms, slaughterhouses, and markets in 12 provinces of China in 2020–2021. The overall prevalence of the qnr gene was 21.13% (56/265), with the highest prevalence in markets (36.11%, 26/72), followed in farms (17.95%, 21/117), and slaughterhouses (10.53%, 9/76). Only the qnrS and qnrB genes were detected, and the prevalence rate of the qnrS gene (19.25%, 51/265) was higher than that of the qnrB gene (1.89%, 5/265). Whole genome sequencing identified 37 distinct AMR genes and 15 plasmid replicons, and the most frequent mutation in quinolone resistance determining regions was parC (T57S; 91.49%, 43/47). Meanwhile, four different qnrS and two qnrB genetic environments were discovered among 47 qnr-positive Salmonella strains. In total, 21.28% (10/47) of the strains were capable of conjugative transfer, and all were qnrS1-positive strains, with the majority of transferable plasmids being IncHI2 types (n = 4). Overall, the prevalence of qnr-positive Salmonella strains from chickens in China and their carriage of multiple resistance and virulence genes and transferable plasmids is a major concern, which calls for continuous surveillance of qnr-positive Salmonella and the development of measures to control its prevalence and transmission.IMPORTANCESalmonella is a common foodborne pathogen responsible for 155,000 deaths annually worldwide. Fluoroquinolones (FQs) are used as first-line drugs for the treatment of Salmonella infections in several countries and regions. However, the emergence and increasing prevalence of the FQ-resistant gene qnr in Salmonella isolated from chickens have been widely reported. Gaining insight into the genetic mechanisms of AMR genes in chicken could lead to the development of preventive measures to control and reduce the risk of drug resistance. In this study, we identified qnr-positive Salmonellae isolated from chickens in different regions of China and their AMR patterns and genome-wide characteristics, providing a theoretical basis for further control of their prevalence and transmission.

Abstract Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2’-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2’-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2’-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.

Abstract Background Metastases within liver or the brain are the most common causes of mortality from lung cancer (LC). Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging but important for early patient intervention. According to mounting evidence, exosomes circulating within blood may facilitate cancer spread by transporting certain proteins for target cells. Methods Using liquid chromatography–MS/MS, we investigated the plasma exosomes’ proteomic profiles derived from 42 metastatic LC patients [16 solitary liver metastasis (LM), together with 26 solitary brain metastasis (BM)] and 25 local advanced (LA) lung cancer cases without metastasis, together with five healthy controls (HC), assessing the LM and BM pathogenesis and find potential novel organ-designated proteomic biomarkers. Using ELISA assay, we verified the expression levels of three plasma exosomal protein biomarkers in 110 LC patients, including 40 solitary LM, 32 solitary BM and 38 LA, and 25 HC. Results In total, 143 and 120 differentially expressed exosome-based proteins (DEEPs) were found to be dysregulated in LM and BM of lung cancer (LM-DEEPs, BM-DEEPs), compared for LA lung cancer samples, respectively. The bioinformatics analyses indicated the heterogeneity and homogeneity in LM-DEEPs and BM-DEEPs. They were primarily engaged within proteomic triggering cascade, ECM-receptor interaction, and the collagen-containing extracellular matrix. Regarding heterogeneity, LM-DEEPs primarily consisted of proteoglycans, lipoprotein, integrin, and heat shock protein, whereas the BM-DEEPs consisted of calcium-dependent/S100 proteins. Furthermore, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)-plasma-stemming exosome proteomics showed heterogeneity, which helped to explain some of the differences between SCLC and NSCLC's metastatic features. We also found that SELL and MUC5B could be used as diagnostic markers of BM, while APOH, CD81, and CCT5 could help diagnose LM in LC patients. Additionally, we demonstrated in a validation cohort that MUC5B and SELL could serve as biomarkers for diagnosing BM, and APOH could be a novel potential diagnostic biomarker of LM. Conclusion We presented the comprehensive and comparative plasma-stemming exosomes’ proteomic profiles from cases of LC who had isolated liver and brain metastases for the first time. We also suggested several possible biomarkers and pathogenic pathways that might be a great starting point for future research on LC metastasis.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

In the aquaculture system of ornamental fish, the interaction between bacterial microbiota and ciliate protozoa can prevent or promote disease outbreaks, and different physicochemical conditions will affect the relationships between them. We investigated the interaction between bacterial microbiota and the parasite Tetrahymena pyriformis when infecting Poecilia reticulata (guppy) under different physicochemical conditions. The abundance of T. pyriformis in water, the relative abundance of bacterial species, and histopathological observation were studied or monitored using environmental DNA (eDNA) extraction technology, the qPCR method, and 16s rRNA sequencing, respectively. The morphological identification and phylogenetic analysis of T. pyriformis were carried out. The infected guppy tissue was also stained by the hematoxylin and eosin methods. The results showed: (1) the bacterial communities of water samples were mainly composed of species assigned to Proteobacteria and Bacteroidetes, and Tabrizicola and Puniceicoccaceae were positively correlated with fish mortality, T. pyriformis abundance, and temperature. (2) Arcicella and Methyloversatilis universalis with different correlations between ciliates appeared in different treatment groups, the result of which proved that environmental factors affected the interaction between bacteria and T. pyriformis. (3) Lower temperatures and a higher pH were more beneficial for preventing disease outbreaks.

Abstract Background Osimertinib is the first‐line treatment for patients with epidermal growth factor receptor (EGFR) mutations, but the treatment options after drug resistance are limited. Previous studies have suggested that EGFR is in an immunosuppressive tumor immune microenvironment (TIME). However, the evolution of TIME after osimertinib resistance and whether this resistance can be overcome by targeting TIME needs to be further investigated. Methods The remodeling process and mechanism of TIME during the treatment with osimertinib were studied. Results The proportion of EGFRL858R+T790M mutant tumor immune infiltrating cells was extremely low. Osimertinib treatment transiently triggered inflammatory cells, but several immunosuppressive cells infiltrated after drug resistance and formed a myeloid‐derived suppressor cell (MDSC)‐enriched TIME. The programmed cell death protein‐1 monoclonal antibody was not able to reverse the MDSC‐enriched TIME. Further analysis revealed that the activation of nuclear factor‐kappa B (NF‐κB) and mitogen‐activated protein kinase (MAPK) pathways recruited a large number of MDSCs via cytokines. Finally, MDSC secreted high levels of interleukin‐10 and arginase‐1 and created an immunosuppressive TIME. Conclusions Thus, our findings lay the foundation for the evolution of TIME in osimertinib treatment, establish the mechanism of immunosuppressive TIME after osimertinib resistance, and propose potential solutions.

Since breast cancer is a heterogeneous disease, there are currently a variety of treatment methods available, including chemotherapy, endocrine therapy, molecular targeted therapy, immunotherapy, radiation therapy, etc. Breast cancer recurrence and metastasis, despite many treatment modalities, constitute a considerable threat to patients’ survival time and pose a clinical challenge that is difficult to tackle precisely. Exosomes have a very special and crucial role in the treatment of drug resistance in breast cancer as a carrier of intercellular communication in the tumor microenvironment. Exosomes and breast cancer treatment resistance have been linked in a growing number of clinical investigations in recent years. This paper covers the status of research on exosomes in the treatment of breast cancer drug resistance and offers theoretical guidance for investigating new strategies to treat breast cancer drug resistance.

Aeromonas schubertii is a pathogen that severely affects aquatic animals, including the snakehead, Channa maculata. Lytic bacteriophages have been recognized as effective alternatives to antibiotics for controlling bacterial infections. However, there have been no reports of A. schubertii phages as far as we know. In this study, a lytic bacteriophage SD04, which could effectively infect A. schubertii, was isolated from pond water cultured with diseased snakehead. The SD04 phage formed small, round plaques on Petri dishes. Electron microscopy revealed a hexagonal head and a contractile tail. Based on its morphology, it may belong to the Myoviridae family. Two major protein bands with molecular weights of 50 and 38 kilodaltons were observed after the phage was subjected to SDS-PAGE. The phage showed a large average burst size, high specificity, and a broad host range. When stored at 4 °C, phage SD04 had high stability over 12 months and showed almost no variation within the first six months. All fish were healthy after both intraperitoneal injection and immersion administration of SD04, indicating the safety of the phage. After treatment with SD04, Channa maculata in both phage therapy groups and prevention groups showed high survival rates (i.e., 83.3 ± 3.3% and 100 ± 1.3%, respectively). Phage therapy inhibits bacterial growth in the liver, the target organ of the infected Channa maculat. The experimental results indicate the potential use of phage SD04 for preventing A. schubertii infection in Channa maculata.

Abstract Tetrahymenosis, caused by about 10 Tetrahymena species, is an emerging problem inflicting a significant economic loss on the aquaculture industry worldwide. However, in the order Tetrahymenida, there are many unresolved evolutionary relationships among taxa. Here we report 21 new sequences, including SSU‐rRNA, ITS1‐5.8S‐ITS2 rRNA and LSU‐rRNA, genes of 10 facultative parasitic Tetrahymena associated with tetrahymenosis, and conduct phylogenetic analyses based on each individual gene and a three‐gene concatenated dataset. The main findings are: (1) All the parasitic and facultative parasitic species cluster in borealis group. (2) With the addition of new sequences, Tetrahymena is still divided into three groups, namely the “borealis group”, the “australis group,” and the “paravorax group.” (3) the cluster pattern of all the newly sequenced facultative parasitic Tetrahymena species shows that members of the “borealis” group may be more susceptible to parasitism. (4) phylogeny based on concatenated genes show that T. pyriformis, T. setosa, and T. leucophrys have close relationship.

Abstract Salmonella is a significant foodborne zoonotic pathogen that endangers both human and animal health. The goal of this research is to gain a preliminary understanding of Salmonella contamination and antimicrobial resistance in the chicken production chain in Hubei Province, China. 1149 animal and environmental samples were collected from chicken farms, slaughterhouses, and retail markets in six cities across Hubei Province in China from 2019 to 2020, yielding Salmonella isolation rates of 4.68% (28/598), 12.21% (47/385), and 9.64% (16/166), respectively. Seventeen distinct serotypes were detected among 53 non-clonal Salmonella strains, of which Meleagridis (26.42%, 14/53) was the dominant serotype. Almost half of the strains (49.06%, 26/53) were multi-drug resistant (MDR). Whole-genome sequencing (WGS) showed that 10 resistance genes (tetA, bla TEM , parC, qnrS1, floR, aac(6′)-Iy, aph(6)-Id, aph(3″)-Ib, aac(6′)-Iaa and sul2) and 7 categories of virulence genes were present in all three links in 22 non-clonal dominant serotype strains. It was shown that Salmonella in the chicken production chain in Hubei Province had a high resistance rate to Tetracycline (TET, 73.58%), Ofloxacin (OFL, 69.81%), Florfenicol (FFC, 60.38%) and Ampicillin (AMP, 39.62%) which was consistent with the widespread use of these drugs in the husbandry industry in China. Salmonella ST types determined by MLST and serotypes determined by WGS had a one-to-one correlation. Minimum spanning tree analysis revealed that there was cross contamination of Salmonella in farms and slaughterhouses, slaughterhouses and markets, animal samples and environmental samples. This work provides useful information for the prevention and control of contamination and antimicrobial resistance of Salmonella in the chicken production chain, as well as demonstrating the dependable role of WGS in Salmonella molecular typing.

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

Viruses are non-living organisms that rely on host cellular metabolism to complete their life cycle. Siniperca chuatsi rhabdovirus (SCRV) has caused huge economic losses to the Chinese perch (Siniperca chuatsi) industry worldwide. SCRV replication is dependent on the cellular glutamine metabolism, while aspartate metabolism plays an important role in viral proliferation in glutamine deficiency. Herein, we investigated roles of asparagine metabolism in SCRV proliferation. Results showed that SCRV infection upregulated the expression of key enzymes in the aspartate metabolic pathway in CPB cells. And the key enzymes of malate-aspartic acid shuttle pathway upregulated during the virus invasion phase, and key enzymes of the asparagine biosynthesis pathway upregulated during the viral replication and release phase. When asparagine was added to the depleted medium, the SCRV copy number restored to 90% of those in replete medium, showing that asparagine and glutamine completely rescue the replication of SCRV. Moreover, inhibition of the aspartate- malate shuttle pathway and knockdown of the expression of key enzymes in the asparagine biosynthesis pathway significantly reduced SCRV production, indicating that the aspartic acid metabolic pathway was required to the replication and proliferation of SCRV. Above results provided references for elucidating pathogenic mechanism of SCRV by regulation of aspartate metabolism.

Objectives: Pharmacists in Nova Scotia have had legislated authority to prescribe since 2011. This study aimed to describe the prescribing activities of pharmacists and the characteristics of patients who used pharmacist prescribing services. Methods: Using provincial health administrative databases we identified all community pharmacists who prescribed during the study period (October 2016 to March 2020) and correspondingly patients who had medications prescribed by a pharmacist during this period. Differences in, and predictors of the quantity of pharmacist prescribing over three fiscal years (April 2017 to March 2020) were described. Pharmacist prescribing activity was compared across the fiscal years of the study period with One-way Analysis of Variance. Negative binomial regression examined patient factors associated with use of pharmacist prescribing services. Analysis was carried out using SAS ENTERPRISE GUIDE v.8.2 (SAS Institute Cary, NC, USA). Key findings: A total of 1182 pharmacist prescribers were identified, who on average prescribed 24.6, 26.3, and 32.5 (p < 0.001) times per month in fiscal years 2018, 2019, 2020, respectively. The patient cohort contained 372,203 Nova Scotians over the 3-year period. For approved common and minor ailment prescribing in Nova Scotia, gastroesophageal reflux disease, vaccines (non-travel), contraceptive management, herpes zoster treatment, and allergic rhinitis had the highest number of prescriptions over the study period. Patient factors most strongly related to receiving more prescribing services by a pharmacist included receiving income assistance without copay (Incidence rate ratio (IRR) = 1.70), having >2 comorbidities (IRR = 1.51), male sex (IRR = 1.03), and greater age (IRR = 1.01). Those from an urban area (IRR = 0.92) or having a higher income (IRR = 0.95) received fewer pharmacist prescribing services (all p < 0.0001). Conclusions: Pharmacist prescribing increased over the 3-year period. Patients who were older and those with multiple comorbidities used pharmacist prescribing services most often. Prescribing activities represent an increasingly utilized role for pharmacists in primary care.

Red sea bream (Pagrosomus major) is one of the most popular farmed marine teleost fish species. Fish cell lines are becoming important research tool in the aquaculture field, and they are suitable models to study fish virology, immunology and toxicology. To obtain a Pagrosomus major cell line for biological studies, a continuous cell line from brain of red sea bream (designated as RSBB cell line) was established and has been successfully subcultured over 100 passages. The RSBB cell line predominantly consisted of fibroblast-like cells and multiplied well in M199 medium supplemented with 10% fetal bovine serum at 28 °C. Karyotyping analysis indicated that the modal chromosome numbers of RSBB cells was 48. After transfection with pEGFP-N1, RSBB cells showed bright green fluorescence with a transfection efficiency approaching 8%. For toxicology study, it was demonstrated that metal Cd could induce cytotoxic effects of RSBB cells, accompanied with a dose-dependent MTT conversion capacity. Morphologically, cells treated with metal Cd produced rounding, shrinking and detaching and induced both cell apoptosis and necrosis. For virology study, the RSBB cells were highly susceptible to Nervous necrosis virus (NNV) and Singapore grouper iridovirus (SGIV) with steady titers (i.e., 108.0~8.3 TCID50 mL−1 and 107.0~7.2 TCID50 mL−1 respectively). Furthermore, an obvious cytopathic effect (CPE) could be observed in RSBB cells infected with Infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdoviruses (SCRV). Meanwhile, all the infections were confirmed by polymerase chain reaction. The new brain cell line developed and characterized from red sea bream in this study could be used as an in vitro model for fish studies in the fields of toxicology and virology.

The area around Poyang Lake is the main aquaculture area in Jiangxi Province, China, and an important base for the supply of freshwater aquatic products. Aquaculture in the Poyang Lake area is severely threatened by diseases caused by bacterial pathogens, and Aeromonas veronii has been the main pathogen in recent years. In this paper, ERIC-PCR genotyping, virulence gene and antimicrobial resistance gene detection, and drug susceptibility tests were carried out on 46 A. veronii isolates obtained from aquaculture systems in the Poyang Lake area from 2016 to 2020. The results showed that the A. veronii strains in the Poyang Lake area had high genetic diversity, and 46 strains produced 36 ERIC genotypes. There were no geographical and temporal differences in the cluster analysis results and no dominant clones. All 13 virulence genes tested were detected, and all isolates had harbored 2 or more virulence genes, with a maximum of 12 virulence genes detected. Among the 22 antimicrobial resistance genes selected, 15 were detected; 97.8% of the isolates contained 2 or more antimicrobial resistance genes, with a maximum of 9 antimicrobial resistance genes. Drug susceptibility tests showed that some strains were resistant to a variety of traditionally effective drugs for Aeromomas, such as enrofloxacin and florfenicol. This study provides a reference for exploring the impact of aquaculture in the Poyang Lake area on public health.

Turbulence is ubiquitous in the planetary boundary layer (PBL), which is of great importance to the prediction of weather and air quality. Nevertheless, the profiles of turbulence in the whole PBL as observed by radar wind profilers (RWPs) are rarely reported. In this communication, the purpose was to investigate the vertical structures of turbulence dissipation rate (ε) obtained from the Doppler spectrum width measurements from two RWPs at plateau (Zhangbei) and plain (Baoding) stations in the North China Plain for the year 2021, and to tease out the underlying mechanism for the difference of ε between Zhangbei and Baoding. Under clear-sky conditions, the annual mean value of ε in the PBL over the plateau station was found to be higher than that over the plain station throughout the daytime from 0900 to 1700 local standard time. The magnitude of ε at both stations showed significant seasonal variation, with the strongest ε in summer but the weakest in winter. If a larger difference between the 2 m air temperature and surface temperature (Ta−Ts), as a surrogate of sensible heat flux, is observed, the turbulence intensity tends to become stronger. The influence of vertical wind shear on turbulence was also analyzed. Comparison analyses showed that the plateau station of Zhangbei was characterized by larger sensible heat flux and stronger wind shear compared with the plain station of Baoding. This may account for the more intense ε within the PBL of Zhangbei. Moreover, the magnitude of ε in the PBL was positively correlated with the values of both Ta−Ts and vertical wind shear. The findings highlight the urgent need to characterize the vertical turbulence structure in the PBL over a variety of surfaces in China.

Objectives: This study aimed to assess the reliability and validity of the Chinese version of the Head and Neck Information Needs Questionnaire (HaNiQ). Methods: The HaNiQ was translated into a Chinese version using internationally recognized forward- and back-translation procedures. The reliability and validity of the HaNiQ were measured using Cronbach’s α coefficient, split-half reliability, exploratory factor analysis, and Pearson correlation analysis. Results: A total of 207 patients in different head and neck cancer (HNC) stages and 174 caregivers completed the Chinese version of the HaNiQ. Internal consistencies varied between good and very well (Cronbach’s α coefficient 0.74–0.90); the split-half coefficient and the content validity index (CVI) of the questionnaire were 83.5% and 83.33%, respectively. The cumulative contribution rates of the 5 subscales in patients with HNCand their caregivers were 62.41% and 61.19%, respectively. However, there are some differences between the Chinese questionnaire for caregiver and the original questionnaire regarding the attribution of items. Items 22, 23, and 27 in the Psychosocial subscale of the English version were assigned to the Survivorship subscale in the Chinese version for caregivers. Conclusions: The results demonstrated that the Chinese version of the HaNiQ is a reliable and valid instrument for measuring the information needs of patients with HNC and that of their caregivers. Though the structure of the Chinese version was different from the English version for caregivers of HNC patients, the Chinese version of the HaNiQ appears to be reliable and would benefit from further testing.

Summary After the occurrence of nitrate‐dependent anaerobic methane oxidation (AMO) in rumen fluid culture was proved, the organisms that perform the denitrifying anaerobic methane oxidizing (DAMO) process in the rumen of dairy goat were investigated by establishing two enrichment culture systems, which were supplied with methane as the sole carbon source and NaNO3 or NaNO2 as the electron acceptor. Several Operational Taxonomic Units (OTU) belonging to Proteobacteria became dominant in the two enrichment systems. The identified Pseudomonas aeruginosa, which was isolated from the NaNO2 enrichment system, could individually perform a whole denitrifying anaerobic methane oxidizing process. Further in vitro rumen fermentation showed that supplementation with the isolated P. aeruginosa could reduce methane emissions, alleviate the nitrite accumulation and prevent the decrease in propionic acid product caused by nitrate supplementation.

The redox homeostasis system regulates many biological processes, intracellular antioxidant production and redox signaling. However, long noncoding RNAs (lncRNAs) involved in redox regulation have rarely been reported. Herein, we reported that downregulation of MAGI2-AS3 decreased the superoxide level in Human fibroblasts (Fbs), a replicative aging model, as detected by the fluorescent probes dihydroethidium (DHE) and MitoSOX™ Red. RNA pulldown combined with mass spectrometry showed that HSPA8 is a novel interacting protein of MAGI2-AS3, which was further confirmed by photoactivatable ribonucleoside–enhanced crosslinking and immunoprecipitation (PAR-CLIP). Downregulation of MAGI2-AS3 decreased the hydrogen peroxide (H2O2) content by stabilizing the HSPA8 protein level via inhibiting the protesome degradation of HSPA8. Further evidence showed that MAGI2-AS3 interacted with the C-terminal domain (CTD) of HSPA8. Downregulation of MAGI2-AS3 delayed cell senescence, while this antiaging effect was abolished by HSPA8 knockdown. The underlying molecular mechanism by which MAGI2-AS3 knockdown inhibited cell senescence was mediated via suppression of the ROS/MAP2K6/p38 signaling pathway. Taken together, these findings revealed that downregulation of lncRNA MAGI2-AS3 decreased the H2O2 content and delayed cell senescence by stabilizing the HSPA8 protein level, identifying a potential antiaging application.

Abstract The toxicity issue of lead hinders large-scale commercial production and photovoltaic field application of lead halide perovskites. Some novel non- or low-toxic perovskite materials have been explored for development of environmentally friendly lead-free perovskite solar cells (PSCs). This review studies the substitution of equivalent/heterovalent metals for Pb based on first-principles calculation, summarizes the theoretical basis of lead-free perovskites, and screens out some promising lead-free candidates with suitable bandgap, optical, and electrical properties. Then, it reports notable achievements for the experimental studies of lead-free perovskites to date, including the crystal structure and material bandgap for all of lead-free materials and photovoltaic performance and stability for corresponding devices. The review finally discusses challenges facing the successful development and commercialization of lead-free PSCs and predicts the prospect of lead-free PSCs in the future.

ABSTRACT Largemouth bass (Micropterus salmoides) is an important and fast-growing aquaculture species in China. In 2017, an epidemic associated with severe mortality occurred in fingerlings of largemouth bass in Guangdong, China. The causative pathogen was identified and named as largemouth bass Birnavirus (LBBV) by virome analysis, viral isolation, electron microscopy, genome sequencing, Western blot, indirect immunofluorescence, experimental challenge, and so on. Virome sequencing results showed that the relative abundance reads related to the family Birnaviridae were the highest, occupied ∼25% of the total viral reads. Electron microscopy revealed large numbers of nonenveloped virus particles in the spleen of diseased fish with a diameter of about 53 nm. LBBV was isolated and propagated in Chinese perch brain cells and induced a typical cytopathic effect. LBBV was stable to chloroform, heat, and 5-bromo-2′-deoxyuridine, but sensitive to acid (pH 3.0). The complete genome of LBBV was comprised of segment A with a size 3525 bp and segment B with a size 2737 bp. Phylogenetic analysis basing on RdRp and VP2 protein sequences revealed that LBBV were clustered into one clade with Lates calcarifer Birnavirus (LCBV), sharing 98.7% or 91.9% sequence identity with LCBV, respectively, but only sharing 59.7% and 52.7% sequence identity with Blosnavirus, suggesting that LBBV and LCBV probably belonged to a new genus. Challenge experiments results indicated that clinical disease symptoms similar to those observed naturally were replicated and the cumulative mortality reached 100% at 3 dpi by i.p. injection. The investigation of prevalence of LBBV infection showed that 41.5% (17/41) sample pools collected from diseased ponds was positive during 2017-2020, indicating that an emerging outbreak of this disease may be spreading within the largemouth bass in China. Above results confirmed that LBBV is a novel Birnavirus associated with massive mortality for fingerlings of largemouth bass. This provides a basis for prevention and control of this emerging viral disease. IMPORTANCE Pathogen isolation and identification are vital for emerging infectious outbreaks. Here we report the isolation, determination and characterization of a novel largemouth bass Birnavirus (LBBV) associated with massive mortality in largemouth bass. And genome of LBBV is determined and analyzed. Based on phylogenetic and alignment analysis of genome, we suggest LBBV belongs to a new genus (designated as Perbirnavirus genus) in Birnaviridae family. Our findings will provide a basis for the further study on prevention and control of this emerging viral disease.

ABSTRACT Under oxidative stress, viruses prefer glycolysis as an ATP source, and glutamine is required as an anaplerotic substrate to replenish the TCA cycle. Infectious spleen and kidney necrosis virus (ISKNV) induces reductive glutamine metabolism in the host cells. Here we report that ISKNV infection the increased NAD+/NADH ratio and the gene expression of glutaminase 1 (GLS1), glutamate dehydrogenase (GDH), and isocitrate dehydrogenase (IDH2) resulted in the phosphorylation and activation of mammalian target of rapamycin (mTOR) in CPB cells. Inhibition of mTOR signaling attenuates ISKNV-induced the upregulation of GLS1, GDH, and IDH2 genes expression, and exhibits significant antiviral activity. Moreover, the expression of silent information regulation 2 homolog 3 (SIRT3) in mRNA level is increased to enhance the reductive glutamine metabolism in ISKNV-infected cells. And those were verified by the expression levels of metabolic genes and the activities of metabolic enzymes in SIRT3-overexpressed or SIRT3-knocked down cells. Remarkably, activation of mTOR signaling upregulates the expression of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene, leading to increased expression of SIRT3 and metabolic genes. These results indicate that mTOR signaling manipulates reductive glutamine metabolism in ISKNV-infected cells through PGC-1α-dependent regulation of SIRT3. Our findings reveal new insights on ISKNV–host interactions and will contribute new cellular targets to antiviral therapy. IMPORTANCE Infectious spleen and kidney necrosis virus (ISKNV) is the causative agent of farmed fish disease that has caused huge economic losses in fresh and marine fish aquaculture. The redox state of cells is shaped by virus into a favorable microenvironment for virus replication and proliferation. Our previous study demonstrated that ISKNV replication induced glutamine metabolism reprogramming, and it is necessary for the ISKNV multiplication. In this study, the mechanistic link between the mTOR/PGC-1α/SIRT3 pathway and reductive glutamine metabolism in the ISKNV-infected cells was provided, which will contribute new insights into the pathogenesis of ISKNV and antiviral treatment strategies.

The LIM domain family genes play a crucial role in various tumors, including non-small-cell lung cancer (NSCLC). Immunotherapy is one of the most significant treatments for NSCLC, and its effectiveness largely depends on the tumor microenvironment (TME). Currently, the potential roles of LIM domain family genes in the TME of NSCLC remain elusive. We comprehensively evaluated the expression and mutation patterns of 47 LIM domain family genes in 1089 NSCLC samples. Using unsupervised clustering analysis, we classified patients with NSCLC into two distinct gene clusters, i.e., the LIM-high group and the LIM-low group. We further investigated the prognosis, TME cell infiltration characteristics, and immunotherapy in the two groups. The LIM-high and LIM-low groups had different biological processes and prognoses. Moreover, there were significant differences in TME characteristics between the LIM-high and LIM-low groups. Specifically, enhanced survival, immune cell activation, and high tumor purity were demonstrated in patients of the LIM-low group, implying an immune-inflamed phenotype. Moreover, the LIM-low group had higher immune cell proportion scores than the LIM-high group and was more responsive to immunotherapy than the LIM-low group. Additionally, we screened out LIM and senescent cell antigen-like domain 1 (LIMS1) as a hub gene of the LIM domain family via five different algorithms of plug-in cytoHubba and the weighted gene co-expression network analysis. Subsequently, proliferation, migration, and invasion assays demonstrated that LIMS1 acts as a pro-tumor gene that promotes the invasion and progression of NSCLC cell lines. This is the first study to reveal a novel LIM domain family gene-related molecular pattern associated with the TME phenotype, which would increase our understanding of the heterogeneity and plasticity of the TME in NSCLC. LIMS1 may serve as a potential therapeutic target for NSCLC.

The Vlasov–Poisson equation is one of the most fundamental models in plasma physics. It has been widely used in areas such as confined plasmas in thermonuclear research and space plasmas in planetary magnetospheres. In this study, we explore the feasibility of the physics-informed neural networks for solving forward and inverse Vlasov–Poisson equation (PINN-Vlasov). The PINN-Vlasov method employs a multilayer perceptron (MLP) to represent the solution of the Vlasov–Poisson equation. The training dataset comprises the randomly sampled time, space, and velocity coordinates and the corresponding distribution function. We generate training data using the fully kinetic PIC simulation rather than the analytical solution to the Vlasov–Poisson equation to eliminate the correlation between data and equations. The Vlasov equation and Poisson equation are concurrently integrated into the PINN-Vlasov framework using automatic differentiation and the trapezoidal rule, respectively. By minimizing the residuals between the reconstructed distribution function and labeled data, and the physically constrained residuals of the Vlasov–Poisson equation, the PINN-Vlasov method is capable of dealing with both forward and inverse problems. For forward problems, the PINN-Vlasov method can solve the Vlasov–Poisson equation with given initial and boundary conditions. For inverse problems, the completely unknown electric field and equation coefficients can be predicted with the PINN-Vlasov method using little particle distribution data.

Changes in terrestrial net primary productivity (NPP) with climate were thought to arise from the direct effects of temperature and precipitation on plant metabolism. However, the change of NPP may be due to the indirect effect of global hydrothermal pattern changes caused by climate change on vegetation distribution. To prove this hypothesis, this study uses land outside Antarctica as the study area, combines temperature and precipitation into standard scores, classifies the globe into four hydrothermal types: warm-wet, warm-dry, cold-wet and cold-dry, analyses changes in hydrothermal patterns since 2000, relates them to changes in NPP, to explains the relationship between changes in global hydrothermal patterns and NPP of vegetation. We found that climate warming reduced the area difference of the four hydrothermal types, which led to the increase of vegetation NPP. The mechanism is mainly manifested in a convergence model of hydrothermal pattern of dry wet transformation (i.e. dry to wet, wet to dry). This shows that the global water and heat distribution has a balanced trend, which is shown as a better resource allocation scheme. This perspective provides a new explanation for the increase in global NPP in terms of global hydrothermal resource allocation, which could enhance the understanding of the impact of global warming on terrestrial vegetation productivity and improve the predictions of global carbon cycle models.

Treatment with immune checkpoint inhibitors (ICIs) has considerably improved prognosis in multiple cancers. However, regardless of PD-L1 expression and TMB, better predictive biomarkers are required to identify ICI-responsive patients. We analyzed a pan-cancer cohort as the discovery cohort to identify the role of Max’s giant associated protein (MGA) mutation in the outcome of ICI treatment in different types of cancers. A pooled lung adenocarcinoma (LUAD) cohort was considered as the validation cohort. Another two LUAD cohorts who received conventional treatment were included for prognostic analysis and mechanism exploration. In the discovery cohort, MGA mutation was a favorable survival biomarker for patients with LUAD than in those with other types of cancers. MGA mutation was positively correlated with the TMB score. The results of the validation cohort were consistent with those of the discovery cohort. Patients with MGA mutation in the TMB-low subgroup had longer survival. Two LUAD cohorts who received standard treatment showed that the MGA mutation was not a prognostic biomarker for standard treatment. Mechanically, we found that the co-mutant genes did not affect the prognostic role of MGA mutation. Gene-set enrichment analysis revealed that genes belonging to the immunodeficiency pathway were enriched in the MGA wild-type group in LUAD. Moreover, activated NK cells were more enriched in the MGA mutant LUAD group. In conclusion, our results demonstrated that MGA mutation was an independent predictive biomarker for ICI therapy. These results may provide a novel insight into identifying potential patients with LUAD for ICI therapy.

Chemical and electrical thrusters are generally utilized to control the attitude and orbit of spacecraft in aerospace. When they are firing, the exhaust expands into the vacuum environment, known as the vacuum plume. The plume flow can collide with spacecraft surfaces due to sufficient expansion, exerting adverse effects on the spacecraft, such as heating load, force/torque, contamination, and sputtering. Therefore, it is vital to investigate the vacuum plume to ensure the function and safety of the spacecraft. This review introduces the ground test and numerical simulation methods of the vacuum plume for chemical and electrical thrusters. The vacuum environment, invasive, and non-invasive (optical) measurements of the ground test are concluded. Numerical simulation of plume flow and its effects is exampled. The hybrid CFD-DSMC (computational fluid dynamics and direct simulation Monte Carlo) algorithm is employed to simulate the gas plume flow spanning continuum and transitional and free molecular flow regimes for chemical thrusters. By contrast, the PIC-DSMC (particle-in-cell plus direct simulation Monte Carlo) algorithm is used for the plasma plume flow containing charged particles exhausted by electrical thrusters. Moreover, the topics of fast prediction of the vacuum plume, plume–surface interaction, and plume–Lunar/Mars regolith interaction are proposed for future research.

Purpose: Previous studies have found that there are significant changes in functional network properties for patients with moderate to severe carotid artery stenosis. Our study aimed to explore the topology properties of brain functional network in asymptomatic patients with carotid plaque without significant stenosis.Methods: A total of 61 asymptomatic patients with carotid plaque (mean age 61.79 ± 7.35 years) and 25 healthy control subjects (HC; 58.12 ± 6.79 years) were recruited. General data collection, carotid ultrasound examination and resting state functional magnetic resonance imaging were performed on all subjects. Graph-theory was applied to examine the differences in the brain functional network topological properties between two groups.Results: In the plaque group, Eloc(P = 0.03), γ (P = 0.01), and σ (P = 0.01) were significantly higher than in the HC group. The degree centrality of left middle frontal gyrus and the nodal efficiency of left middle frontal gyrus and right inferior parietal angular gyrus were significantly higher in the plaque group than in HC. The degree centrality and betweenness centrality of right middle temporal gyrus, as well as the nodal efficiency of right middle temporal gyrus, were significantly lower in the plaque group than in HC.Conclusions: The brain functional networks of patients with carotid plaques differ from those of healthy controls. Asymptomatic patients with carotid plaques exhibit increased local and global connectivity, which may reflect subtle reorganizations in response to early brain damage.

BackgroundThe endoplasmic reticulum oxidoreductin-1-like (ERO1L) gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia, however, the role of ERO1L in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in lung adenocarcinoma (LUAD).MethodsIn this study, raw datasets (including RNA-seq, methylation, sgRNA-seq, phenotype, and survival data) were obtained from public databases. This data was analyzed and used to explore the biological landscape of ERO1L in immune infiltration. Expression data was used to characterize samples. Using gene signatures and cell quantification, stromal and immune infiltration was determined. These findings were used to predict sensitivity to immunotherapy.ResultsThis study found that ERO1L was significantly overexpressed in LUAD in comparison to normal tissue. This overexpression was found to be a result of hypomethylation of the ERO1L promoter. Overexpression of ERO1L resulted in an immune-suppressive TIME via the recruitment of immune-suppressive cells including regulatory T cells (Tregs), cancer associated fibroblasts, M2-type macrophages, and myeloid-derived suppressor cells. Using the Tumor Immune Dysfunction and Exclusion (TIDE) framework, it was identified that patients in the ERO1Lhigh group possessed a significantly lower response rate to immunotherapy in comparison to the ERO1Llow group. Mechanistic analysis revealed that overexpression of ERO1L was associated with the upregulation of JAK-STAT and NF-κB signaling pathways, thus affecting chemokine and cytokine patterns in the TIME.ConclusionsThis study found that overexpression of ERO1L was associated with poor prognoses in patients with LUAD. Overexpression of ERO1L was indicative of a hypoxia-induced immune-suppressive TIME, which was shown to confer resistance to immunotherapy in patients with LUAD. Further studies are required to assess the potential role of ERO1L as a biomarker for immunotherapy efficacy in LUAD.

Clogging of sump strainers that filter the recirculation water in containment after a loss-of-coolant accident (LOCA) seriously impedes the continued cooling of nuclear reactor cores. In experiments examining the corrosion of aluminium alloy 6061, a common material in containment equipment, in borated solutions simulating the water chemistry of sump water after a LOCA, we found that Fe-bearing intermetallic particles, which were initially buried in the Al matrix, were progressively exposed as corrosion continued. Their cathodic nature vis-à-vis the Al matrix provoked continuous trenching around them until they were finally released into the test solution. Such particles released from Al alloy components in a reactor containment after a LOCA will be transported to the sump entrance with the recirculation flow and trapped by the debris bed that typically forms on the strainer surface, potentially aggravating strainer clogging. These Fe-bearing intermetallic particles, many of which had a rod or thin strip-like geometry, were identified to be mainly the cubic phase αc-Al(Fe,Mn)Si with an average size of about 2.15 μm; 11.5 g of particles with a volume of about 3.2 cm3 would be released with the dissolution of every 1 kg 6061 aluminium alloy. Keywords: Aluminium corrosion, Strainer clogging, Intermetallic, Loss-of-coolant accident

Abstract The present study was performed to evaluate the effects of different concentration of rumen-protected methionine (RPMet) with a low level of crude protein (CP) using rumen simulation technology on many parameters. The experiment was assigned randomly into four treatments: (1) high protein diet (163.39 g/kg CP) without RPMet (HP); (2) low protein diet (146.33 g/kg CP) without RPMet (LP); (3) low protein diet, supplement with low RPMet (RPMet: 0.11 g/kg) (LPLMet); and (4) low protein diet, supplement with high RPMet (RPMet: 0.81 g/kg) (LPHMet), mixed with 20 g basal diet in each fermenter. Based on National Research Council (NRC) (Nutrient requirements of dairy cattle, National Academies Press, Washington, DC, 2001) recommendation for dairy ruminants HP diet was formulated as positive normal control and LP as a negative control. Results demonstrated that CP disappearance was found significantly higher (P 0.05) with LP. However, neutral detergent fiber (NDF) and gross energy (GE) were found a parallel among supplement groups compared to HP and higher than LP. Furthermore, microbial crude protein, total and short chain fatty acids were found similar in LPHMet and HP and found significantly higher than LPLMet and LP. The R. albus population of LPHMet found parallel to HP and pointedly higher than LP in a solid and liquid fraction. Daily production of ammonia nitrogen, total gas, and methane were higher in HP than LP, LPLMet, and LPHMet. Overall, results concluded that values of digestibility, rumen fermentation, microbial crude protein, and R. albus population were similar of LPHMet to that of HP group. However, production of ammonia-N, total gas, and methane volume were significantly higher in the HP group than LPLMet, LPHMet, and LP groups. In conclusion, rumen-protected methionine is a good feed supplement to low dietary protein in the level of 0.81 g/kg.

Abstract Background Increasing evidence has demonstrated that mesenchymal stem cells (MSCs) play a role in the construction of tumor microenvironments. Co-culture between tumor cells and MSCs provides an easy and useful platform for mimicking tumor microenvironments and identifying the important members involved in tumor progress. The long non-coding RNAs (lncRNAs) have been shown to regulate different tumorigenic processes. In this study, we aimed to examine functional lncRNA deregulations associated with breast cancer malignancy instigated by MSC-MCF-7 co-culture. Methods The microarrays were used to profile the expression changes of lncRNAs in MCF-7 cells during epithelial-mesenchymal transition (EMT) induced by co-culture with MSCs. We found that an intergenic lncRNA KB-1732A1.1 (termed LincK, partly overlapped with GASL1) was significantly elevated. To investigate the biological function of LincK, the expression of EMT markers, cell migration, invasion, proliferation, and colony formation were evaluated in vitro and xenograft assay in nude mice were performed in vivo. Furthermore, we detected LincK expression in clinical samples using RNAscope® technology and verified aberrant expression of LincK in breast cancer data sets from The Cancer Genome Atlas (TCGA) by bioinformatic analysis. The underlying mechanisms of LincK were investigated using mRNA microarray analyses, Western blot, RNA pull down, and RNA immunoprecipitation. Results LincK induced an EMT progress in breast cancer cells (BCC) MCF-7, MDA-MB-453, and MDA-MB-231. The depletion of LincK decreased the growth, migration, and invasion in BCC, whereas the overexpression of LincK exerted the opposite effects. Moreover, knockdown of LincK repressed tumorigenesis, and ectopic expression of LincK promoted tumor growth in MCF-7 xenograft model. LincK ablation in MDA-MB-231 cells dramatically impaired lung metastasis when incubated intravenously into nude mice. Further, LincK was frequently elevated in breast cancer compared with normal breast tissue in clinical samples. Mechanistically, LincK may share common miRNA response elements with PBK and ZEB1 and regulate the effects of miR-200 s. Conclusion LincK plays a significant role in regulating EMT and tumor growth and could be a potential therapeutic target in breast cancer.

Profiling the vertical atmospheric structure for typhoons remains challenging. Here, the atmospheric dynamic and thermodynamic structures were investigated during the passage of Typhoon Sinlaku (2020) over Xisha Islands in the South China Sea for the period 28 July to 2 August 2020, mainly based on two-way rawinsonde and dropsonde measurements in combination with surface-based automatic weather station observations, disdrometer measurements, and Himawari-8 geostationary satellite images. The study period was divided to three stages: the formation stage of tropical depression (pre-TD), tropical depression (TD), and tropical storm (TS). The wind speed and local vertical wind shear reached the maximum value at 3 km above mean sea level (AMSL) before the typhoon approached the Xisha islands. Pseudo-equivalent potential temperature (θse) was found to decrease with the altitude below 2 km AMSL; temperature inversions occurred frequently within this altitude range, particularly during the TS stage. This seemed a typical capping inversion that indicated a downward motion above 2 km AMSL. The temperature increased slightly with the development of Typhoon Sinlaku (2020) at altitudes of 8–10 km AMSL. This indicated that our observations presumably captured the air mass warmed by the condensation, which was a good signature of an upper air in the tropical cyclone. In addition, wind speed (particularly in the lower stratosphere), specific humidity, and equivalent potential temperature escalated significantly when the tropical depression strengthened into Typhoon Sinlaku (2020), which indicated that the typhoon constantly obtained energy from the sea surface during its passage over the study region. The thermodynamic and dynamic structures of atmosphere advance our understanding of the inner structure of typhoons during the different evolutionary stages.

α-CsPbI3 nanocrystals (NCs) with poor stability prevent their wide applications in optoelectronic fields. Ca2+ (1.00 Å) as a new B-site doping ion can successfully boost CsPbI3 NC performance with both improved phase stability and optoelectronic properties. With a Ca2+/Pb2+ ratio of 0.40%, both phase and photoluminescence (PL) stability could be greatly enhanced. Facilitated by increased tolerance factor, the cubic phase of its solid film could be maintained after 58 days in ambient condition or 4 h accelerated aging process at 120°C. The PL stability of its solution could be preserved to 83% after 147 days in ambient condition. Even using UV light to accelerate aging, the T50 of PL could boost 1.8-folds as compared to CsPbI3 NCs. Because Ca2+ doping can dramatically decrease defect densities of films and reduce hole injection barriers, the red light-emitting diodes (LEDs) exhibited about triple enhancement for maximum the external quantum efficiency (EQE) up to 7.8% and 2.2 times enhancement for half-lifetime of LED up to 85 min. We believe it is promising to further explore high-quality CsPbI3 NC LEDs via a Ca2+-doping strategy.

The impact of drought on terrestrial ecosystem Gross Primary Productivity (GPP) is strong and widespread; therefore, it is important to study the response of terrestrial ecosystem GPP to drought. In this paper, we compared the correlations of Sun-induced Chlorophyll fluorescence (SIF), Enhanced Vegetation Index (EVI), and Normalized Differential Vegetation Index (NDVI) with the drought index sc_PDSI, estimated GPP in Yunnan Province, China, based on SIFTOTAL data (SIF data with canopy effects eliminated), and analyzed the response characteristics of GPP to drought for one mega-drought event (2009–2011) in combination with the sc_PDSI drought index. The results show that SIF is more sensitive to drought than the NDVI and EVI; the correlation between the GPP estimated based on SIF data (GPPSIF) and the actual observed flux values (R2 = 0.83) is better than GPPGLASS and GPPLUE, and the RMSE is also lower than those two products. This drought has a serious impact on GPP, and the monthly average values of the effect of drought on GPP (GPPd) in Yunnan Province in 2009, 2010, and 2011 are −11.37 gC·m−2·month−1, −23.48 gC·m−2·month−1 and −17.92 gC·m−2·month−1, which are 8.6%, 17.48% and 13.85% of the monthly average in a normal year, respectively. The spatial variability of GPP response to drought is significant, which is mainly determined by the degree, and duration of the drought, the vegetation type, the topography, and anthropogenic factors. In conclusion, GPPSIF quickly and accurately reflects the process of this drought, and this study helps to elucidate the response of GPP to drought conditions and provides more scientific information for drought prediction and ecosystem management.

Abstract Congenital heart disease (CHD) is the major cause of morbidity/mortality in infancy and childhood. Using a mouse model to uncover the mechanism of CHD is essential to understand its pathogenesis. However, conventional 2D phenotyping methods cannot comprehensively exhibit and accurately distinguish various 3D cardiac malformations for the complicated structure of heart cavity. Here, a new automated tool based on microcomputed tomography (micro‐CT) image data sets known as computer‐assisted cardiac cavity tracking (CACCT) is presented, which can detect the connections between cardiac cavities and identify complicated cardiac malformations in mouse hearts automatically. With CACCT, researchers, even those without expert training or diagnostic experience of CHD, can identify complicated cardiac malformations in mice conveniently and precisely, including transposition of the great arteries, double‐outlet right ventricle and atypical ventricular septal defect, whose accuracy is equivalent to senior fetal cardiologists. CACCT provides an effective approach to accurately identify heterogeneous cardiac malformations, which will facilitate the mechanistic studies into CHD and heart development.

Antimicrobials inhibit cecal fermentation when preventing rabbit from infection. This study aimed to evaluate the effect of supplementation with two combinations of alternative to antimicrobial (combination I: 1 × 109 cfu/kg Bacillus subtilis + 2 g/kg fructooligosaccharide; combination II: 2 g/kg acidifier and 0.6 g/kg essential oil) by stages on rabbit's growth performance and cecal fermentation. Two hundred and forty 15-day-old male kits with similar body weight were distributed randomly to five groups, which were control (basal diet), ZnB (addition of 0.1 g/kg bacitracin zinc in basal diet), II (addition of combination II), I-II (addition of combination I during days 15-35, addition of combination II during days 36-77), and I-II-I (supplemented with combination I during days 15-35 and 57-77, supplemented with combination II during days 36-56). Each group had 6 replicates. One healthy rabbit from each replicate was slaughtered at day 35 and day 77. The results showed: (1) at day 35, the two combinations and bacitracin zinc all inhibited ileal Escherichia coli (P < 0.05), decreased cecal pH, and increased total volatile fatty acid concentration (P < 0.05). Combination І decreased duodenal crypt depth and increased duodenal villi height to crypt depth ratio (VCR) (P < 0.05); (2) at day 77, I-II-I group had more cecal total bacteria than control (P < 0.05). Mode I-II or I-II-I increased cecal Bacteroides-Prevotella (P < 0.05) compared with ZnB. Mode I-II-I shortened duodenal crypt depth and increased VCR compared with control or ZnB (P < 0.05); (3) after weaning, modes I-II-I and I-II had better or similar effect on decreasing diarrhoea and mortality rate compared with ZnB. In conclusion, both modes had better or similar effect on decreasing diarrhoea and mortality rate compared with inclusion of antimicrobial or combination II alone during the whole trial, and mode I-II-I showed better effect than mode I-II.

Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P

The aim of this work was to investigate the dispersibility of kaolinite-rich coal gangue in rubber matrix, the mechanical properties and thermal stability of coal gangue/styrene butadiene rubber (SBR) composites, and to compare these properties to those of the same coal gangue but had undergone thermal activation and modification. Several experimental techniques, such as X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric-differential scanning calorimetry (TG-DSC), laser-scattering particle analyzer were adopted to characterize the coal gangue particles and then the obtained composites. The results demonstrated the raw coal gangue (RCG) was mainly composed of kaolinite. Calcination led to amorphization of thermal activated coal gangue (ACG), increased hydrophilicity and void volume, and decreased pH. The grain size of ACG became coarser than RCG, but ACG turned loose confirmed by higher degree of refinement after grinding. Modification enhanced the hydrophobicity of the coal gangue and improved its dispersibility than fillers without modification. Calcined samples had better dispersibility than uncalcined fillers. Additionally, the coal gangue treated by calcinating, grinding and modifying (MGA) had the best dispersion in rubber matrix. Either calcination or modification could improve the mechanical properties and thermal stability of coal gangue filled rubber, while the performance of MGA reinforced SBR (MGA-SBR) was the best. The enhanced performance of the MGA-SBR was owed to better dispersion of particles as well as stronger interactions between particles and rubber macromolecules.

Infectious spleen and kidney necrosis virus (ISKNV) resulted in severe systemic diseases with high morbidity and mortality in Siniperca chuatsi. Vaccination is the primary method for effective prevention and control of these diseases. The development of inactivated ISKNV vaccines made some progress, but the technique of quality evaluation is scarce. Herein, a measurement of the MCP (major capsid protein) antigen concentration for the inactivated ISKNV vaccine was developed by double-antibody sandwich ELISA. Firstly, mouse monoclonal antibodies against ISKNV particles and MCP were generated. Then, a double-antibody sandwich ELISA was developed using the monoclonal antibody 1C8 1B9 as the capture antibody and Biotin-3B12 6B3 as the detection antibody. A standard curve was generated using the MCP concentration versus OD value with the linear range of concentration of 4.69~300 ng/mL. The assay sensitivity was 0.9 ng/mL. The antigen content of three batches of inactivated ISKNV vaccines was quantitatively detected using the double-antibody sandwich ELISA. The results showed that MCP antigen contents of inactivated ISKNV vaccines were positively correlated with the viral titers. The newly established double-antibody sandwich ELISA provided a useful tool for the detection of antigen quality for ISKNV inactivated vaccines.