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BackgroundRisk scores for predicting in-hospital major bleeding in patients with acute myocardial infarction (AMI) are rare. The Swedish web-system for the enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) score (SS), consisting of five common clinical variables, is a novel model for predicting in-hospital major bleeding. External validation of SS has not yet been completed.Methods and resultsA retrospective study recruiting consecutive East Asian patients diagnosed with AMI was conducted in the Second Affiliated Hospital, Zhejiang University. The primary endpoint was the ability of SS to predict in-hospital major bleeding, which was defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. To validate SS, the discrimination and calibration were assessed in the overall population and several subgroups. The receiver operating characteristic (ROC) curves and the areas under ROC curves (AUCs) were calculated for discrimination. The calibration of SS was evaluated with the unreliability U test. A total of 2,841 patients diagnosed with AMI during hospitalization were included, and 1.94% (55) of them experienced in-hospital major bleeding events. The AUC of SS for the whole population was only 0.60 [95% confidence interval (CI), 0.52–0.67], without an acceptable calibration (p = 0.001). Meanwhile, the highest AUC (0.72; 95% CI, 0.61–0.82) of SS for the primary endpoint was found in the diabetes subgroup, with an acceptable calibration (p = 0.87).ConclusionThis external validation study showed that SS failed to exhibit sufficient accuracy in predicting in-hospital major bleeding among East Asian patients with AMI despite demonstrating acceptable performance in the diabetic subgroup of patients. Studies to uncover optimal prediction tools for in-hospital major bleeding risk in AMI are urgently warranted.

Abstract Aimed to investigate the associations between different growth patterns with high blood pressure, and further examine the mediation effect of BMI between growth patterns and high blood pressure among children and adolescents. A total of 31581 children and adolescents aged 7–18 years were selected based on the stratified cluster sampling method. Logistics regression models were used to calculate the odds rations (ORs) and 95% confidence interval (95%CI) of the association between different growth patterns and high blood pressure. Mediation effect analyses were applied to estimate the effect of BMI on the increase of blood pressure levels in different growth patterns. In different sex and ages, compared to reference group of normal growth, blood pressure levels and prevalence of high blood pressure of the catch‐up growth were higher, but that of the catch‐down growth were lower. The prevalence of high blood pressure was 11.69%, 16.06%, and 9.68% in normal growth, catch‐up growth, and catch‐down growth, respectively. In total, compared with the normal growth pattern, the ORs (95%CI) of high blood pressure, high systolic blood pressure and high diastolic blood pressure in the catch‐up growth were 1.171(1.073,1.280), 1.110(1.001,1.230) and 1.141(1.025,1.270) (p

Abstract Background This study aims to examine interocular differences in the choroidal thickness and vascular density of the choriocapillaris in anisometropic myopes and to further explore the relationship between choroidal blood flow and myopia. Methods The sample comprised 44 participants with anisometropic myopia, aged 9 to 18 years, with normal best-corrected visual acuity. All participants underwent a series of examinations, including spherical equivalent refraction (SER) and axial length (AL), measured by a Lenstar optical biometer and optical coherence tomography angiography (OCTA) scanner. OCT measured the choroidal thickness, vascular density, and flow voids of the choriocapillaris, and a customized algorithm was implemented in MATLAB R2017a with the post-correction of AL. The choroidal thickness was measured at the fovea and 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm nasally, temporally, inferiorly, and superiorly to the fovea. The vascular density and the flow voids of the choriocapillaris were measured at a 0.6-mm-diameter central circle, and the 0.6–2.5 mm diameter circle in the nasal, temporal, inferior, and superior regions. Repeated-measured ANOVAs were used to analyze the interocular differences. Partial correlations with the K value and age adjustments were used to study the relationships between the choroidal thickness, the choriocapillaris vascular density and flow voids, the SER and AL. Results The choroidal thickness of the more myopic eyes was significantly thinner than less myopic eyes (P ≤ 0.001), and the flow voids in the more myopic eyes were more than less myopic eyes (P = 0.002). There was no significant difference in the vascular density of the choriocapillaris between the more and less myopic eyes (P = 0.525). However, when anisometropia was more than 1.50 D, the vascular density of choriocapillaris in the more myopic eyes was significantly less than the less myopic eyes (P = 0.026). The interocular difference of the choroidal thickness was significantly correlated with the interocular difference in SER and AL in the center, superior, and inferior regions but not in the nasal or temporal regions. The interocular differences of the vascular density and the flow voids of the choriocapillaris were not correlated with the interocular difference of SER and AL. Conclusions The choroidal thickness is thinner in the more myopic eyes. The flow void is increased, and the vascular density of the choriocapillaris is reduced in the more myopic eyes of children with anisometropia exceeding 1.50 D.

Abstract Background Workers in electronics manufacturers may be exposed to various occupational hazards such as isopropanol, lead, and noise. Telomeres are special segments of cap-like DNA protein complex at end of liner chromosomes in eukaryotic cells. Telomere length is a potential marker of genetic damage. The aim of this study is to evaluate the effect of occupational hazards on the relative telomere length (rTL) of peripheral blood cells of workers in an electronics manufacturer, and to explore whether relative telomere length could be a biomarker for assessing genetic damage in the electronics manufacturing industry. Methods We investigated a large-scale electronics manufacturer in the Pearl River Delta Region. We ultimately collected 699 qualified workers (248 with isopropanol exposure, 182 with lead exposure, 157 with noise exposure, and 112 controls). During physical examination of the workers, we gave them questionnaires to understand their health statuses and living habits. We also collected peripheral blood samples from these workers to test exposure levels and rTL in the leucocytes. Results The concentrations of air isopropanol in all monitored workshops was 25.3 mg/m3 and air lead smoke was 0.020 mg/m3. The maximum equivalent continuous A sound level noise exposure position was 82.2dB (A). All were lower than those in the Occupational Exposure Limits in Workplaces in China. Urinary acetone in the isopropanol exposed group was 1.04 (0, 1.50) mg/L, and cumulative urinary acetone was 1.48 (0, 5.09) mg-years/L. Blood lead levels (BLLs) were 28.57 (22.77, 37.06) µg/dL, and cumulative blood lead levels (CBLLs) were 92.75 (55.47, 165.13) µg-years/dL. rTL was different between occupational exposed workers and controls: rTL was 0.140 units (95 % CI: 0.022, 0.259) shorter in lead exposed workers and 0.467 units (95 % CI: 0.276–0.658) shorter in noise exposed workers compared to the controls. There is no statistical difference in rTL between isopropanol exposure workers and the controls. In order to elucidate the relationship between rTL and occupational hazards exposure, we divided the isopropanol exposure workers into three groups (0, ~1.43 mg/L, and >1.43 mg/L). None of the rTL difference was statistically significant among exposed workers at different uroacetone levels (P>0.05). The groups with ≥100 µg/dL blood lead had shorter rTL than the group with blood lead below 100 µg/dL (F=4.422, P=0.013). We incorporated age, gender, birthplace, race, education level, smoking, and alcohol consumption into the linear regression equation. Only blood lead concentration (X) was entered into the regression equation, yielding a multivariate linear regression equation of Y=0.397-0.124X (F=8.091, P=0.005). Workers with different hearing loss also had statistically significant differences in rTL (F=5.731, P=0.004). rTL was a protective factor for the occurrence of noise-induced hearing loss (NIHL). The longer the rTL, the lower the risk of NIHL [OR=0.64 (0.42, 0.98)]. Conclusions rTL was shorter in lead exposed workers and noise exposed workers, and it was a protective factor for the occurrence of the noise-induced hearing loss. Thus, rTL of peripheral blood may be a sensitive marker of genetic damage among workers in environments with lead and noise exposure.

Abstract Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Background: The fingers’ tactile sensibility is essential in surgery, especially in microsurgery. Therefore, surgeons seeking to improve their performance often prefer certain glove brands and wearing habits. There is the need of objectively testing these glove wearing conditions and determine the effect of surgical experience with regard to tactile sensibility by comparing surgeons with non-surgeons. Methods: This cross-sectional single-center pilot-study was conducted between June and August 2021. Two groups of 27 surgeons and 27 non-surgeons underwent two-point-discrimination (2PD) and Semmes-Weinstein monofilament testing (SWMT) of both index fingers with bare hands and with wearing six different brands of surgical gloves. Different wearing conditions, such as single-gloving, double-gloving, well-fitted, under- and oversized gloves, were evaluated within and between the groups. Results: Most glove types decreased tactile sensibility (2PD and SWMT) of surgeons and non-surgeons. Interestingly, the thinnest gloves showed similar 2PD values to bare hands in both groups. Double-gloving negatively impacted SWMT, without influencing 2PD. Undersized gloves showed better 2PD and SWMT than well-fitted gloves, while oversized gloves showed no tactile drawbacks. With bare hands and certain glove conditions, the surgeons' 2PD and SWMT was significantly better than the non-surgeons’, indicating a positive effect of surgical experience on tactile sensibility. Conclusion: Our study demonstrated the positive impact of surgical experience on tactile sensibility, as demonstrated by the surgeons. The sensibility of the gloved hand varies on the surgical glove type, but favors thinner gloves, single gloving (rather than double gloving) and undersized or well-fitted gloves.

ObjectiveOur study aimed to evaluate the influence of methylenetetrahydrofolate reductase (MTHFR) polymorphism on the clinical features and therapeutic effects in patients with migraine.MethodsThe data of 135 patients with migraine were collected from January 2021 to December 2021. The MTHFR C677T polymorphism was analyzed. The pain intensity was evaluated using a numerical rating scale (NRS) during treatment. The levels of folic acid, homocysteine (Hcy), vitamin B12, interleukin-2 (IL-2), IL-4, and ferritin, and changes of NRS were compared between folic acid and conventional treatment groups stratified by different genotypes of MTHFR in migraine patients.ResultsThe levels of Hcy and ferritin in male patients were higher than that in female patients (P < 0.05); Compared with CC and CT genotype groups, the TT genotype group showed significantly higher Hcy levels (P < 0.05) and lower folic acid levels (P < 0.05); In both folic acid and conventional treatment groups, a significant decrease in NRS score was observed in different genotypes post-treatment (P < 0.05). Patients with TT genotype in the folic acid treatment group showed better therapeutic efficacy than conventional treatment group (P < 0.05). There is no significant difference in the therapeutic efficacy in other genotypes between the two groups (P > 0.05).ConclusionThe MTHFR C677T genotyping may provide a new method to guide and optimize individualized medication for migraine patients.

Background: Human serum albumin (HSA) is a commonly used medication for the treatment of sepsis. However, there is no conclusive evidence as to whether different concentrations of HSA are associated with patient prognosis. This study aimed to evaluate the association between different concentrations of HSA and 28-day mortality in patients with sepsis.Methods: The data for this retrospective study were collected from the Medical Information Mart for Intensive Care IV database. Patients with sepsis were divided into two groups according to the concentration of HSA received: 25% and 5% HSA. The primary outcome of this study was the 28-day mortality in patients with sepsis. To ensure the robustness of our findings, we used multivariate Cox regression, propensity score matching, double-robust estimation, and inverse probability weighting models.Results: A total of 76,943 patients were screened, of whom 5,009 were enrolled. 1,258 and 3,751 patients received 25% and 5% HSA, respectively. The 28-day mortality rate was 38.2% (481/1,258) for patients in the 25% HSA group and 8.7% (325/3,751) for patients in the 5% HSA group. After propensity score matching, 1,648 patients were identified. The inverse probability weighting model suggested that 5% HSA received was associated with lower 28-day mortality (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.54–0.73, p < 0.001). Subgroup and sensitivity analysis confirmed the robustness of the results.Conclusion: In patients with sepsis, 5% HSA received may be associated with a lower risk of 28-day mortality than 25% HSA. Further randomized controlled trials are required to confirm this association.

In this study, an analytical method based on the modified QuEChERS and gas chromatography tandem mass spectrometry was proposed to determine 15 phthalic acid esters in edible oils including dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, dibutyl phthalate, bis(4-methyl-2-pentyl) phthalate, bis(2-ethoxyethyl) phthalate, dipentyl phthalate, dihexyl phthalate, benzyl butyl phthalate, bis(2-n-butoxyethyl) phthalate, dicyclohexyl phthalate, di-n-heptyl phthalate, diphenyl phthalate, di-n-octyl phthalate, and dinonyl phthalate. Calibration curves with good correlation coefficients (R > 0.990) were obtained in the range of 4–2000 μg kg−1. The LODs and LOQs were from 0.02 to 8.00 μg kg−1 and from 0.07 to 26.68 μg kg−1, respectively, which were significantly lower than the previous studies. Moreover, good recoveries varied from 70.11 % to 115.33 %, while repeatability ranged from 3.97 % to 11.55 %. The results showed that DBP, DIBP, and DEHP were detected in edible oils. The foregoing findings suggested that the proposed approach might be used to detect phthalic acid esters in edible oils.

Hydrolysis of Mg-based materials is considered as a potential means of safe and convenient real-time control of H2 release, enabling efficient loading, discharge and utilization of hydrogen in portable electronic devices. At present work, the hydrogen generation properties of MgLi-graphite composites were evaluated for the first time. The MgLi-graphite composites with different doping amounts of expanded graphite (abbreviated as EG hereinafter) were synthesized through ball milling and the hydrogen behaviors of the composites were investigated in chloride solutions. Among the above doping systems, the 10 wt.% EG-doped MgLi exhibited the best hydrogen performance in MgCl2 solutions. In particular, the 22 h-milled MgLi-10 wt.% EG composites possessed both desirable hydrogen conversion and rapid reaction kinetics, delivering a hydrogen yield of 966 mL H2 g−1 within merely 2 min and a maximum hydrogen generation rate of 1147 mL H2 min−1 g−1, as opposed to the sluggish kinetics in the EG-free composites. Moreover, the EG-doped MgLi showed superior air-stable ability even under a 75 RH% ambient atmosphere. For example, the 22 h-milled MgLi-10 wt.% EG composites held a fuel conversion of 89% after air exposure for 72 h, rendering it an advantage for Mg-based materials to safely store and transfer in practical applications. The similar favorable hydrogen performance of MgLi-EG composites in (simulate) seawater may shed light on future development of hydrogen generation technologies.

Glaciers are crucial water resources for arid inland rivers in Northwest China. In recent decades, glaciers are largely experiencing shrinkage under the climate-warming scenario, thereby exerting tremendous influences on regional water resources. The primary role of understudying watershed scale glacier changes under changing climatic conditions is to ensure sustainable utilization of regional water resources, to prevent and mitigate glacier-related disasters. This study maps the current (2020) distribution of glacier boundaries across the Kaidu-Kongque river basin, south slope of Tianshan Mountains, and monitors the spatial evolution of glaciers over five time periods from 2000–2020 through thresholded band ratios approach, using 25 Landsat images at 30 m resolution. In addition, this study attempts to understand the role of climate characteristics for variable response of glacier area. The results show that the total area of glaciers was 398.21 km2 in 2020. The glaciers retreated by about 1.17 km2/a (0.26%/a) from 2000 to 2020. The glaciers were reducing at a significantly rapid rate between 2000 and 2005, a slow rate from 2005 to 2015, and an accelerated rate during 2015–2020. The meteorological data shows slight increasing trends of mean annual temperature (0.02°C/a) and annual precipitation (2.07 mm/a). The correlation analysis demonstrates that the role of temperature presents more significant correlation with glacier recession than precipitation. There is a temporal hysteresis in the response of glacier change to climate change. Increasing trend of temperature in summer proves to be the driving force behind the Kaidu-Kongque basin glacier recession during the recent 20 years.© 2021 China Geology Editorial Office.

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. Results This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. Conclusions This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.

IntroductionRadiotherapy (RT) is currently the main treatment for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Due to the short survival time and obvious adverse reactions of RT, we urgently need more appropriate treatment. This network meta-analysis reviewed the efficacy and adverse effects of radiotherapy-based combination therapy for patients without targeted epidermal growth factor receptor (EGFR) mutations/anaplastic lymphoma kinase (ALK) gene rearrangement NSCLC BMs, to screen out the therapy with the best efficacy.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from the earliest publication date available to 1 April 2022. STATA15.0 was used to conduct heterogeneity analysis, sensitivity analysis, forest plot analysis, and publication bias analysis.ResultsA total of 28 studies, involving 3707 patients were included in the Bayesian network meta-analysis. In the limited paired meta-analysis for head-to-head comparative trials, compared with RT-based combination therapy, RT combined with Immune checkpoint inhibitors (ICIs) showed significant overall survival (OS) benefit (HR 0.65, 95%CI 0.47–0.9, p

Round bamboo has aroused much interest in construction for its mechanical properties, but poor biological durability seriously restricts its application. In order to develop a suitable and effective preservative treatment method for round bamboo, copper naphthenate (CuN) was adopted and impregnated into round bamboo using heat-cold procedure. The distribution and retention of copper naphthenate in round bamboo were studied, and the biological durability represented by the mould and decay resistance were investigated. The results showed that the retention and fixation of copper reached 0.39 kg⋅m−3 and 85.3%, respectively. Scanning electron microscopy–energy dispersive X-ray spectrometry further disclosed an increasing trend in the composition of CuN from the end inward. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses later revealed that CuN could be fixed on bamboo in the form of hydrogen bond or complex reaction. Statistical analysis showed that the increasing concentration of CuN from 0.3% to 0.5% and 0.8% (calculated as Cu2+ content) has significant contribution against Trametes versicolor and Gloeophyllum trabeum in comparison with the untreated bamboo. Meanwhile, when the concentration of treating solution increased to 0.8 wt%, the resisting efficacy for Aspergillus niger, Penicillium citrinum and Trichoderma viride soared as high as 85.9%, 94.8% and 70.3%, respectively.

Objectives Complement activation is a critical feature in the development of systemic lupus erythematosus (SLE). Whether there are changes of complement components in the urine of SLE has not been reported. The aim of the study was to evaluate the complement-related proteins in the urine of SLE, verify differentially expressed proteins(DEPs) in the active phase of SLE, further explore their clinical application value. Methods First, we used bioinformatics and functional enrichment to screen and identify the urine protein profile of SLE patients. Then, analyzed and verified the proteins related to the complement pathway by western-blot and Parallel Reaction Monitoring (PRM) technology. Further evaluated the relationship between urinary DEPs related to complement pathway and disease activity. Results A total of 14 complement pathway-related proteins were screened for differences in expression between the active group and the stable group, eight of these DEPs were up-regulated and six were down-regulated. These DEPs may play a key role in SLE disease activity. We used PRM technology to verify the eight up-regulated proteins, and found that four of these complement proteins, namely C9, C8A, C4B, and C8G, were significantly increased in active group. Furthermore, these four DEPs were highly correlated with disease activity. In the urine of SLE patients, AUCs of 0.750, 0.840, 0.757 and 0.736 were achieved with C9, C8A, C4B, and C8G, respectively. Conclusions Complement-related DEPs in urine have a certain correlation with SLE disease activity. Urine C9, C8A, C4B and C8G present promising non-invasive biomarkers for monitoring lupus activity.

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto’s thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto’s thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto’s thyroiditis.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2–5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Aflatoxin B1 (AFB1) is kind of a common mycotoxin in food and feedstuff. Aquafeeds are susceptible to contamination of AFB1. In teleost fish, the spleen and head kidney are key immune organ. Moreover, the fish skin is a critical mucosal barrier system. However, there was little study on the effects of dietary AFB1 on the immune response of these immune organs in fish. This study aimed to explore the impacts of oral AFB1 on the immune competence and its mechanisms in the skin, spleen, and head kidney of grass carp. Our work indicated that dietary AFB1 reduced antibacterial compounds and immunoglobulins contents, and decreased the transcription levels of antimicrobial peptides in grass carp immune organs. In addition, dietary AFB1 increased the transcription levels of pro-inflammatory cytokines and reduced the transcription levels of anti-inflammatory cytokines in the grass carp immune organs, which might be regulated by NF-κB and TOR signaling, respectively. Meanwhile, we evaluated the content of AFB1 in the grass carp diet should not exceed 29.48 μg/kg diet according to the levels of acid phosphatase and lysozyme. In summary, dietary AFB1 impaired immune response in grass carp skin, spleen, and head kidney.

BackgroundExtensive epidemiological studies have highlighted the correlation between serum phosphate and cardiovascular diseases. The present study aims to determine whether genetically predicted serum phosphate is causally associated with the distinct subtypes of cardiovascular events through the use of Mendelian randomization (MR) analysis.MethodsIndependent and strongly correlated single-nucleotide polymorphisms (SNPs) for serum phosphate were extracted from publicly available genome-wide association studies. Summary statistics of cardiovascular diseases were derived from large-scale consortiums, including HERMES and FinnGen biobank. MR-Egger, weighted median, inverse variance weighted, pleiotropy residual sum and outlier (MR-PRESSO) methods and MR using robust adjusted profile score (MR-RAPS) were employed to analyze causality. The sensitivity analyses comprised heterogeneity, horizontal pleiotropy, and leave-one-out approaches; these were used to ensure the stability of the results.ResultsOur study demonstrated that increased genetically predicted serum phosphate is causally associated with a higher risk of valvular heart disease (VHD) [For VHD including rheumatic fever: odds ratio (OR) = 2.45; 95% confidence interval (CI), 1.52–3.94; p = 0.0002; for non-rheumatic VHD: OR = 6.58; 95% CI, 2.50–17.32; p = 0.0001]. However, no causal association was detected between serum phosphate and other common cardiovascular diseases (including coronary heart disease, heart failure, atrial fibrillation, and essential hypertension).ConclusionsThe results indicate strong causality between serum phosphate and valvular heart disease. Serum phosphate-lowering therapy within the physiological range may represent a novel therapeutic method for valvular heart disease.

Sclerotinia sclerotiorum, a worldwide distributed fungal pathogen, causes serious adverse effects on the yield and seed quality of rapeseed. Polygalacturonase-inhibiting proteins (PGIPs) can protect the cell wall from degradation by pathogen-secreted polygalacturonases (PGs). The present study found several PGIPs from Oryza sativa, especially OsPGIP6 and 3 have much higher inhibitory activities to SsPGs than BnPGIP2 from Brassica napus. Among them, OsPGIP1, 4, 6 can significantly elevate the resistance of transgenic Arabidopsis to S. sclerotiorum. Subsequently, OsPGIP1, 3, 4, 6 were subjected to SSR resistance assay in transgenic rapeseed plants. Among which, OsPGIP6 showed the highest resistance to S. sclerotiorum. At 48 h after detached leaves inoculation, the lesion area of OE-OsPGIP6 rapeseed plants is only 17.93% of the non-transgenic line, and 22.17, 21.32, 52.78, 56.47%, compared to OE-BnPGIP2, OE-OsPGIP1, OE-OsPGIP2, OE-OsPGIP4, respectively. Furthermore, the lesion area of OE-OsPGIP6 reached 10.11% compared to WT at 72 hpi. Also, the lesion length on the stem of OE-OsPGIP6 plants was reduced by 36.83% compared to WT. These results reveal that OsPGIP family, especially OsPGIP6, has a great potential in rapeseed S. sclerotiorum-resistance breeding.

Objectives To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2ndG/3rdG) inhibitors versus first-generation (ALK-1stG) inhibitors.Design The study is in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Randomised controlled trials (RCTs) published up to 3 November 2021 were retrieved from PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov.Setting RCTs from any country and healthcare setting.Participants Patients with advanced ALK-positive NSCLC with or without brain metastases.Interventions and comparisons The interventions were ALK-2ndG/3rdG; the control arm was ALK-1stG or crizotinib.Primary and secondary outcome measures Primary outcomes included median progression-free survival and median OS. Secondary outcomes included systemic objective response rate, intracranial response rate and rate of grade ≥3 adverse events (AEs).Results A total of 12 RCTs involving 3156 patients were analysed. Compared with ALK-1stG (crizotinib), ALK-2ndG (alectinib, brigatinib, ceritinib and ensartinib) significantly improved the OS (HR: 0.72, 95% CI: 0.57 to 0.90, p=0.004) and intracranial response of patients with any brain metastases, especially with measurable (diameter ≥10 mm) brain metastases. Network meta-analysis demonstrated that ALK-3rdG (lorlatinib) had superior efficacy for patients with brain lesions, but performed a distinct side-effect profile. Moreover, alectinib showed superior efficacy and lower toxicity in ALK-positive NSCLC.Conclusion Treatment with ALK-2ndG inhibitors significantly improved OS compared with crizotinib, and alectinib has less severe AEs than any other ALK inhibitors with moderate-high efficacy. The limited OS follow-up and inadequate sample sizes might contribute to having no statistically significant difference in OS of lorlatinib versus crizotinib. More high-quality and longer follow-up RCTs are warranted to prove our findings.PROSPERO registration number CRD42021292245.

BackgroundRed blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.MethodsWe conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.ResultsA total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.ConclusionOur study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.

In recent years, mannose oligosaccharide (MOS) as a functional additive is widely used in aquaculture, to enhance fish immunity. An evaluation of the effect of dietary MOS supplementation on the immune barrier function and related signaling molecules mechanism of grass carp (Ctenopharyngodon idella) was undertaken in the present study. Six diets with graded amounts of MOS supplementation (0, 200, 400, 600, 800, and 1000 mg/kg) were fed to 540 grass carp over 60 days. To examine the immune response and potential mechanisms of MOS supplementation on the intestine, a challenge test was conducted using injections of Aeromonas hydrophila for 14 days. Results of the study on the optimal supplementation with MOS were found as follows (1) MOS enhances immunity partly related to increasing antibacterial substances content and antimicrobial peptides expression; (2) MOS attenuates inflammatory response partly related to regulating the dynamic balance of intestinal inflammatory cytokines; (3) MOS regulates immune barrier function may partly be related to modulating TLRs/MyD88/NFκB and TOR/S6K1/4EBP signalling pathways. Finally, the current study concluded that MOS supplementation could improve fish intestinal immune barrier function under Aeromonas hydrophila infected conditions.

Coronary heart disease (CHD) is a type of cardiovascular disease with the highest mortality rate worldwide. Percutaneous transluminal coronary intervention (PCI) is the most effective method for treating CHD. However, in-stent restenosis (ISR), a long-term complication after PCI, affects the prognosis of patients with CHD. Previous studies have suggested that hypersensitivity reactions induced by metallic components may be one of the reasons of this complication. With the emergence of first- and second-generation drug-eluting stents (DES), the efficacy and prognosis of patients with CHD have greatly improved, and the incidence of ISR has gradually decreased to less than 10%. Nevertheless, DES components have been reported to induce hypersensitivity reactions, either individually or synergistically, and cause local inflammation and neointima formation, leading to long-term adverse cardiovascular events. In this article, we described the relationship between ISR and hypersensitivity from different perspectives, including its possible pathogenesis, and discussed their potential influencing factors and clinical significance.

BackgroundAs a metabolic disease, any abnormality in the aerobic oxidation pathway of glucose may lead to the occurrence of diabetes. This study aimed to investigate the changes in proteins related to aerobic oxidative metabolism in urinary exosomes of diabetic patients and normal controls of different ages, and to further verify their correlation with the pathogenesis of diabetes.MethodsSamples were collected, and proteomic information of urinary exosomes was collected by LC-MS/MS. ELISA was used to further detect the expression of aerobic and oxidative metabolism-related proteins in urinary exosomes of diabetic patients and normal controls of different ages, and to draw receiver operating characteristic (ROC) curve to evaluate its value in diabetes monitoring.ResultsA total of 17 proteins involved in aerobic oxidative metabolism of glucose were identified in urinary exosome proteins. Compared with normal control, the expressions of PFKM, GAPDH, ACO2 and MDH2 in diabetic patients were decreased, and the expression of IDH3G was increased. The concentrations of PFKM, GAPDH and ACO2 in urinary exosomes were linearly correlated with the expression of MDH2 (P

BackgroundAs one of the key criteria to differentiate benign vs. malignant tumors in ovarian and other solid cancers, tumor-stroma reaction (TSR) is long observed by pathologists and has been found correlated with patient prognosis. However, paucity of study aims to overcome subjective bias or automate TSR evaluation for enabling association analysis to a large cohort.Materials and methodsServing as positive and negative sets of TSR studies, H&E slides of primary tumors of high-grade serous ovarian carcinoma (HGSOC) (n = 291) and serous borderline ovarian tumor (SBOT) (n = 15) were digitally scanned. Three pathologist-defined quantification criteria were used to characterize the extents of TSR. Scores for each criterion were annotated (0/1/2 as none-low/intermediate/high) in the training set consisting of 18,265 H&E patches. Serial of deep learning (DL) models were trained to identify tumor vs. stroma regions and predict TSR scores. After cross-validation and independent validations, the trained models were generalized to the entire HGSOC cohort and correlated with clinical characteristics. In a subset of cases tumor transcriptomes were available, gene- and pathway-level association studies were conducted with TSR scores.ResultsThe trained models accurately identified the tumor stroma tissue regions and predicted TSR scores. Within tumor stroma interface region, TSR fibrosis scores were strongly associated with patient prognosis. Cancer signaling aberrations associated 14 KEGG pathways were also found positively correlated with TSR-fibrosis score.ConclusionWith the aid of DL, TSR evaluation could be generalized to large cohort to enable prognostic association analysis and facilitate discovering novel gene and pathways associated with disease progress.

The Bagridae fish family holds significant economic value and enjoys a high demand in the commercial market due to its desirable characteristics, such as delicious meat, fewer muscle spines, and a pleasing flavor. In recent years, the Bagridae has experienced rapid development in the seed industry in response to industry demands. Researchers have conducted extensive studies on genetic breeding in the Bagridae, employing a comprehensive breeding approach that combines conventional breeding techniques with innovative new technologies and cooperative efforts. In this review, we present an overview of the market situation and discuss various breeding processes applied to the Bagridae, including selective breeding, genetic engineering breeding, cell engineering breeding, molecular marker-assisted breeding, and hybrid breeding. Additionally, we focus on introducing the cultivation methods for two new Bagridae varieties. Furthermore, we explore and summarize the breeding conditions, genetic background, heterosis, comprehensive breeding technology, stress resistance, and metabolic nutrition of hybrid Bagridae catfishes. Overall, noticeable heterosis has been observed in the breeding of the hybrid yellow catfish “Huangyou-1”, which exhibits promising market prospects and economic benefits for aquaculture. Our study aims to underscore the importance of harnessing the heterosis of catfish, particularly the Pelteobagrus and Bagridae species. Consequently, this review provides an update on the current available information regarding the seed industry of the Bagridae fish family.

The paper discussed the use of machine learning (ML) and quantum chemistry calculations to predict the transition state and yield of copper-catalyzed P–H insertion reactions. By analyzing a dataset of 120 experimental data points, the transition state was determined using density functional theory (DFT). ML algorithms were then applied to analyze 16 descriptors derived from the quantum chemical transition state to predict the product yield. Among the algorithms studied, the Support Vector Machine (SVM) achieved the highest prediction accuracy of 97%, with over 80% correlation in Leave-One-Out Cross-Validation (LOOCV). Sensitivity analysis was performed on each descriptor, and a comprehensive investigation of the reaction mechanism was conducted to better understand the transition state characteristics. Finally, the ML model was used to predict reaction plans for experimental design, demonstrating strong predictive performance in subsequent experimental validation.

This study was designed to examine the protective effects of the extract of mulberry (Morus alba L.) leaves (EML) on crucian carp (Carassius auratus) against a high stocking density, Cu exposure and trichlorfon exposure, which adversely impact fish growth performance, feed intake and fish locomotion. High stocking densities decreased the activities of amylase, lipase, trypsin, Na+/K+-ATPase and alkaline phosphatase (AKP), and increased the content of malonaldehyde (MDA) in fish digestive organs, indicating an impairment of the digestive function and a disturbance of the antioxidant status. Cu exposure increased the activities of glutamate–oxaloacetate transaminase (GOT) and glutamate–pyruvate transaminase (GPT) in fish digestive organs, suggesting the activation of amino acid metabolism. Furthermore, trichlorfon exposure reduced the activities of lactate dehydrogenase (LDH), glutathione reductase (GR), GOT and GPT, and the capacities of the anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR) in fish muscles, indicating a disruption of the bioenergetic homeostasis and antioxidant status. Our present study indicates that dietary EML supplementation relieved the detrimental effects induced by these stressors.

In this study, a fast and non-destructive method was proposed to analyze rapeseed quality parameters with the help of NIR hyperspectral imaging spectroscopy and chemometrics. Hyperspectral images were acquired in the reflectance mode. Meanwhile, the region of interest was extracted from each image by the regional growth algorithm. The kernel partial least square regression was used to build prediction models for crude protein content, oil content, erucic acid content, and glucosinolate content of rapeseed. The results showed that the correlation coefficients were 0.9461, 0.9503, 0.9572, and 0.9335, whereas the root mean square errors of prediction were 0.5514%, 0.5680%, 2.8113%, and 10.3209 µmol/g for crude protein content, oil content, erucic acid content, and glucosinolate content, respectively. It demonstrated that NIR hyperspectral imaging is a promising tool to determine rapeseed quality parameters in a rapid and non-invasive manner.

The objective of this study was to investigate the effects of Scoparia dulcis extract (SDE) on stress induced by high stocking density and Cu and trichlorfon exposure in crucian carp (Carassius auratus). The results showed that these stressors exerted detrimental effects in fish, such as inhibition of growth performance, reduced feed intake, and interruption of fish locomotion. Under high stocking density, dietary SDE supplementation increased the content of reduced glutathione (GSH) and the activities of amylase, catalase (CAT), and glutathione reductase (GR) and decreased the content of malonaldehyde (MDA) in the intestine of crucian carp. A similar trend was presented in the hepatopancreas under Cu exposure. Dietary SDE supplementation enhanced the activities of CAT, superoxide dismutase (SOD), glutathione peroxidase (GPx), lactate dehydrogenase, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase in the muscle of crucian carp under trichlorfon exposure. The optimum dietary SDE supplementation levels were 4.07, 4.33, and 3.95 g kg−1 diet based on the recovery rate of weight gain (RWG), feed intake (FI), and inhibitory rate of rollover (IR) for crucian carp under high stocking density and Cu and trichlorfon exposure, respectively. Overall, dietary supplementation with SDE may be a useful nutritional strategy for relieving these stresses in aquatic animals.

A tree skeleton reflects the geometric and structural characteristics of a tree. Terrestrial laser scanning (TLS) provides an effective means to construct tree skeletons that can capture the surface and topological features of trees. However, it is difficult to construct a tree skeleton located at the geometric centre of the tree with a detailed hierarchy of branches because of the natural intricate topology of the tree and the defects of the tree point cloud scanned by TLS. In this study, we presented a tree-skeletonization method based on density-based spatial clustering of applications with noise (DBSCAN) using TLS data. First, outliers were removed using DBSCAN, and the point-traversal order of each point was recorded. Next, a tree point cloud was divided into several tree slices using contour planes, and several tree segments were obtained by applying DBSCAN to each tree slice. Tree skeleton points were retrieved from each tree segment after the point-inversion transformation. Then, the adjacent relationship between skeleton points and the flow weight of each skeleton point was calculated based on the point-traversal order. After that, the skeleton points were classified into stems and different levels of branch points using the flow weights of the skeleton points, and the branch hierarchies were identified. Finally, the tree skeleton was optimized using the angle consistency. The positional deviation dp and directivity deviation dd were presented in this study to verify the validity of the constructed tree skeleton. From the visualization results, the constructed tree skeleton effectively reflected the geometrical structure and branch hierarchies of the tree. The averages of dp and dd were 0.418 cm and 8.474 degrees, respectively. The results demonstrated the validity of the presented method. It will help improve the visualization and accurate measurement of trees.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage defects remains challenging in terms of maintaining chondrogenic phenotype during in vitro chondrocyte expansion. Growth factor supplementation has been found supportive in improving ACI outcomes by promoting chondrocyte redifferentiation. Here, we analysed the chondrogenic growth factor concentrations in the human blood-derived secretome of Hypoxia Preconditioned Serum (HPS) and assessed the effect of HPS-10% and HPS-40% on human articular chondrocytes from osteoarthritic cartilage at different time points compared to normal fresh serum (NS-10% and NS-40%) and FCS-10% culture conditions. In HPS, the concentrations of TGF-beta1, IGF-1, bFGF, PDGF-BB and G-CSF were found to be higher than in NS. Chondrocyte proliferation was promoted with higher doses of HPS (HPS-40% vs. HPS-10%) and longer stimulation (4 vs. 2 days) compared to FCS-10%. On day 4, immunostaining of the HPS-10%-treated chondrocytes showed increased levels of collagen type II compared to the other conditions. The promotion of the chondrogenic phenotype was validated with quantitative real-time PCR for the expression of collagen type II (COL2A1), collagen type I (COL1A1), SOX9 and matrix metalloproteinase 13 (MMP13). We demonstrated the highest differentiation index (COL2A1/COL1A1) in HPS-10%-treated chondrocytes on day 4. In parallel, the expression of differentiation marker SOX9 was elevated on day 4, with HPS-10% higher than NS-10/40% and FCS-10%. The expression of the cartilage remodelling marker MMP13 was comparable across all culture conditions. These findings implicate the potential of HPS-10% to improve conventional FCS-based ACI culture protocols by promoting the proliferation and chondrogenic phenotype of chondrocytes during in vitro expansion.

Based on previous researches, we further investigated the multi-silique trait in rapeseed (Brassica napus L.) line zws-ms. In this study, we used a relatively comprehensive list of flowering related genes in rapeseed and compared them between zws-ms and its near-isogenic line (NIL) zws-217. Genes were studied on genome, transcriptome and proteome levels and then we focused on genes with non-synonymous single nucleotide polymorphism (SNP) or frame-shift insertion-deletion (InDel), finding some genes on the list which changes their sequences. Then, combined with their annotation and the information of their orthologs, certain genes such as BnaA09g05900D, ortholog of AGAMOUS-LIKE 42 (AGL42), which encodes an MADS-box protein, were assumed as probably responsible for the multi-silique trait. Also, we analyzed the Differentially Accumulated Proteins (DAPs) between zws-ms and zws-217, revealing some genes involved in homologous recombination and mismatch repair pathways. Since the development of flowers/siliques is crucial to crops and it influences the yield of rapeseed, this study paved a way to deeply understand the mechanism of the multi-pistil flower formation, which may facilitate researches on rapeseed production in future.

Recently, wireless power transfer (WPT) technology has attracted much attention and shown rapid development. However, a fundamental challenge emerges in practical applications: how to achieve robust power transfer against the variation of operating conditions, such as the fluctuation of transfer distance, as well as the relative orientation of resonant coils. In this article, we theoretically propose and experimentally demonstrate that the robustness of a parity-time (PT) asymmetric system with unbalanced gain-loss working in a weak coupling region can be improved significantly, compared with that of a PT-symmetric system with balanced gain-loss working in a strong coupling region under the premise that the system works at a fixed optimal frequency. A pure real mode known as bound state in the continuum (BIC) in the weak coupling region of the PT-asymmetric system is adopted to ensure the high efficiency and stability of the WPT and break the limitations of balanced gain-loss of the PT-symmetric system. The better robustness performance originates from the orthogonal state with a pure real eigenmode embedded in the weak coupling region. Further experiments also verify that the PT-asymmetric system can achieve higher efficiency than that of the PT-symmetric system. In addition, we discuss the performance of the WPT system based on the theories of coupled mode theory (CMT) and circuit theory (CT); the BIC in the framework of CMT and a perfect impedance matching condition in the framework of CT for efficient power transfer are consistent. We also conducted power experimental verification of 30 watts, and found the efficiency between the coils can reach over 90% in dynamic scenarios, which meets expectations. The presented framework extends the field of non-Hermitian physics, bridges the gap between the non-ideal PT-symmetric system and a practical engineering application, and introduces a novel WPT mechanism for flexible application scenarios. Our results could provide instructive significance for practical applications of the WPT system in the long term.

Abstract Background Fractional flow reserve (FFR) is a widely used gold standard to evaluate ischemia-causing lesions. A new method of non-invasive approach, termed as AccuFFRct, for calculating FFR based on coronary computed tomography angiography (CCTA) and computational fluid dynamics (CFD) has been proposed. However, its diagnostic accuracy has not been validated. Objectives This study sought to present a novel approach for non-invasive computation of FFR and evaluate its diagnostic performance in patients with coronary stenosis. Methods A total of 54 consecutive patients with 78 vessels from a single center who underwent CCTA and invasive FFR measurement were retrospectively analyzed. The CT-derived FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of AccuFFRct and CCTA in detecting hemodynamically significant coronary artery disease (CAD) was evaluated using the invasive FFR as a reference standard. Results Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for AccuFFRct in detecting FFR ≤ 0.8 on per-patient basis were 90.7, 89.5, 91.4, 85.0 and 94.1%, respectively, while those of CCTA were 38.9, 100.0, 5.71, 36.5 and 100.0%, respectively. The correlation between AccuFFRct and FFR was good (r = 0.76 and r = 0.65 on per-patient and per-vessel basis, respectively, both p

Abstract As an essential component of power transformers, the detection and diagnosis of incipient partial discharge (PD) activities of bushings are of great significance. A 35‐kV oil‐impregnated paper (OIP) bushing is investigated. The bushing is modelled by coaxial theory and electromagnetic (EM) simulation. As the paths of PD‐induced ultra‐high frequency (UHF) signal propagating in the bushing are OIPs and oil gap, small attenuation during signal propagation is seen. Since OIP is composed of heterogeneous media compared with pure oil, there will be relatively less UHF signal leakage from OIPs, whereas more leakage from the oil gap. This leakage provides the possibility of non‐contact detection outside the bushing by UHF method. PD measurements with UHF method are carried out on the bushing. Then, the minimum energy method is used to extract time‐difference‐of‐arrival (TDOA), and Chan algorithm is adopted to locate points of UHF signal radiation. High accuracy locating with a small error of 15 cm has been achieved. The contactless UHF method‐based tests have demonstrated the effectiveness of online monitoring and locating of bushing PD.

Vibrational spectroscopy is one of the most commonly applied techniques for determining molecular structures. Conventional applications often involve extensive expertise or expensive first-principles computational effort in order to establish one-to-one spectrum-structure relationships. Here we developed a machine-learning protocol to correlate spectral fingerprints with local molecular structures. Our protocol enables not only quick and accurate prediction of infrared (IR) absorption and Raman vibrational spectra based on molecular structures, but more importantly, also enables structure recognition of chemical groups from vibrational spectral features. IR and Raman spectral features arising from different selection rules were recurrently fed to the model to achieve a nearly zero error rate in structure recognition. Both the spectrum prediction and structure recognition models have good transferability, implying a high possibility of being extended to various spectral or non-spectral characteristics. This machine learning protocol may provide impovements to real-time field applications in many areas of spectroscopy.

Abstract This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium‐potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood‐brain barrier and blood‐brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.

Limited strength and ductile joints for bonding γ-TiAl intermetallics are one of the main concerns on γ-TiAl applications in the aerospace industry. In this study, a new ductile brazing filler with TiZrCuNi system was developed by an established model for calculating the electrons distribution of the unit cell for the filler. Three kinds of fillers with fixed amount of Cu and Ni as 25 wt.%, but different Zr level (25, 18, 10 wt.%) were designed. It was found that the filler diffusion was affected by the filler composition, which was insufficient with high Zr content up to 37.5 wt.%. And the defects such as the voids and the cracks were observed with medium Zr level as 25 wt.% and brazing temperature as 1000 °C. The sound joints by Zr as 18 wt.% and 10 wt.% filler at 950 °C and 980 °C respectively were achieved with tensile strength as 520 MPa–570 MPa at room temperature. This tensile strength was remained as 495 MPa in average at 600 °C. The strong joints were attributed to the fine, randomly oriented Ti3Al grains and evenly distributed elements at the interfaces.

Abstract As an environmentally friendly and high-density energy carrier, hydrogen has been recognized as one of the ideal alternatives for fossil fuels. One of the major challenges faced by “hydrogen economy” is the development of efficient, low-cost, safe and selective hydrogen generation from chemical storage materials. In this review, we summarize the recent advances in hydrogen production via hydrolysis and alcoholysis of light-metal-based materials, such as borohydrides, Mg-based and Al-based materials, and the highly efficient regeneration of borohydrides. Unfortunately, most of these hydrolysable materials are still plagued by sluggish kinetics and low hydrogen yield. While a number of strategies including catalysis, alloying, solution modification, and ball milling have been developed to overcome these drawbacks, the high costs required for the “one-pass” utilization of hydrolysis/alcoholysis systems have ultimately made these techniques almost impossible for practical large-scale applications. Therefore, it is imperative to develop low-cost material systems based on abundant resources and effective recycling technologies of spent fuels for efficient transport, production and storage of hydrogen in a fuel cell-based hydrogen economy.

Abstract Background Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Thus, the aim of this study was to investigate the protective effect and mechanism of sodium butyrate (SB) on RV-induced apoptosis of IPEC-J2 cells. Results The RV infection led to significant cell apoptosis, increased the expression levels of ER stress (ERS) markers, phosphorylated protein kinase-like ER kinase (PERK), eukaryotic initiation factor 2 alpha (eIF2α), caspase9, and caspase3. Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis. The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78 (GRP78), PERK, and eIF2α. In addition, SB treatment restrained the ERS-mediated apoptotic pathway, as indicated by downregulation of C/EBP homologous protein (CHOP) mRNA level, as well as decreased cleaved caspase9 and caspase3 protein levels. Furthermore, siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis. Conclusions These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2α signaling pathway via GPR109a, which provide new ideas for the prevention and control of RV.

Abstract Power transformers play a vital role in power transmission systems from the energy source to the consumption center. In situ diagnostics of the performance of power transformers provides a variety of benefits to ensure reliable electricity transmission. Immunity to electromagnetic interference, high sensitivity, high insulation as well as small dimensions of optical sensing make it very attractive for applications in power transformer monitoring. This paper presents a critical review of various diagnostic methods for power transformers such as partial discharge, dissolved gases, temperature and other important sensing, and optical detection. The advantages and disadvantages of different monitoring methods are carefully discussed and assessed. Finally, the existing technical barriers and future prospects of optical monitoring methods for power transformers are presented.

BackgroundContinuously growing of HIV incidence among men who have sex with men (MSM), as well as the low rate of HIV testing of MSM in China, demonstrates a need for innovative strategies to improve the implementation of HIV prevention. The use of machine learning algorithms is an increasing tendency in disease diagnosis prediction. We aimed to develop and validate machine learning models in predicting HIV infection among MSM that can identify individuals at increased risk of HIV acquisition for transmission-reduction interventions.MethodsWe extracted data from MSM sentinel surveillance in Zhejiang province from 2018 to 2020. Univariate logistic regression was used to select significant variables in 2018–2019 data (P < 0.05). After data processing and feature selection, we divided the model development data into two groups by stratified random sampling: training data (70%) and testing data (30%). The Synthetic Minority Oversampling Technique (SMOTE) was applied to solve the problem of unbalanced data. The evaluation metrics of model performance were comprised of accuracy, precision, recall, F-measure, and the area under the receiver operating characteristic curve (AUC). Then, we explored three commonly-used machine learning algorithms to compare with logistic regression (LR), including decision tree (DT), support vector machines (SVM), and random forest (RF). Finally, the four models were validated prospectively with 2020 data from Zhejiang province.ResultsA total of 6,346 MSM were included in model development data, 372 of whom were diagnosed with HIV. In feature selection, 12 variables were selected as model predicting indicators. Compared with LR, the algorithms of DT, SVM, and RF improved the classification prediction performance in SMOTE-processed data, with the AUC of 0.778, 0.856, 0.887, and 0.942, respectively. RF was the best-performing algorithm (accuracy = 0.871, precision = 0.960, recall = 0.775, F-measure = 0.858, and AUC = 0.942). And the RF model still performed well on prospective validation (AUC = 0.846).ConclusionMachine learning models are substantially better than conventional LR model and RF should be considered in prediction tools of HIV infection in Chinese MSM. Further studies are needed to optimize and promote these algorithms and evaluate their impact on HIV prevention of MSM.

BackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10−8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10−5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.ResultsBased on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 – 1.10, P = 1.67 × 10−4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75–0.93, P = 7.76 × 10−4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74–0.92, P = 4.15 × 10−4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.ConclusionOur findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species — peristaltic contraction–inhibiting bacterium (PIB) — that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

IntroductionThe relationship between the characteristics of puberty growth and the stature (height and overweight and obesity) in late adolescence was not clear. We aimed to explore the effects of puberty growth patterns on the stature in late adolescence.MethodsA total of 13,143 children from a longitudinal cohort from 2006 to 2016 in Zhongshan city of China were included. The Preece–Baines growth curve was fitted for each individual child, and the age at peak height velocity (APHV), peak height velocity (PHV), and age at take-off (TOA) were obtained from the Preece–Baines model. To compare the difference in height in late adolescence (at 18 years old) at different pubertal height growth patterns (height spurt timing, intensity, and duration), the height at baseline was matched by using the propensity score matching. The log-binomial model was applied to assess the association between the three pubertal height growth patterns (timing, intensity, and duration) and overweight and obesity status in late adolescence, controlling the urbanity and body mass index (BMI) at baseline.ResultsAfter matching the baseline height, boys and girls in three pubertal patterns with early timing (P < 0.01), small intensity (P < 0.01), and short duration (P < 0.01) of height spurt had the lowest final height in the late adolescence. A 16% increase and 45% increase of risk for overweight and obesity were significantly associated with the early APHV in boys and girls, respectively, relative risk (RR) in boys, 1.16(95% confidence interval, CI: 1.03–1.30), P = 0.011; RR in girls, 1.45(1.21–1.75), P < 0.001. A 21% increase and 59% increase of risk for overweight and obesity were significantly associated with small PHV in boys and girls, respectively, RR in boys, 1.21(1.07–1.36), P < 0.001; RR in girls, 1.59(1.30–1.95), P < 0.001; and an 80% increase of risk for overweight and obesity with small spurt duration in girls (RR = 1.80; 95% CI: 1.49, 2.18; P < 0.001).ConclusionPubertal growth patterns, including earlier puberty onset timing, smaller puberty intensity, and shorter puberty spurt duration, had a positive association with lower height risks and higher overweight and obesity risks in late adolescence.

Ditchless rice-crayfish co-culture is an emerging model of rice-crayfish farming that circumvents the potential hazards of digging ditches in traditional rice-crayfish farming. However, due to the complex interactions among crayfish, ambient microbiota, and environmental variables, it is necessary to assess the differences in bacterial structure between ditchless and traditional rice-crayfish culture. In this study, the crayfish culture area in the Sichuan basin was selected as the study area, and the bacterial communities of two rice-crayfish culture systems were compared by high-throughput sequencing of 16S rDNA. The results showed that the ditchless system had lower water depth, higher dissolved oxygen, lower total ammonia nitrogen and lower morbidity. There are intuitive differences in the composition of environmental bacterial communities due to environmental changes, even if they are similar in composition at the phylum level. Microbiota in sediments from ditchless systems appear to produce less ammonia nitrogen. The abundance of the pathogens colonizing the intestine of ditchless crayfish was lower than ditched one, and the composition was similar to water. Ditch-farmed crayfish appear to be more susceptible to environmental microbes and have a more fragile intestinal structure. Water depth and dissolved oxygen are the main environmental factors that determine the distribution of microbiota. This study is the first to investigate the bacterial ecology of a ditchless rice- crayfish farming system. The results show that the ditchless rice-crayfish culture model has a more superior bacterial system than the traditional rice-crayfish culture.