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Highlights Photoresponsive black phosphorus (BP)/Ti3C2Tx composites were synthesized by a self-assembly strategy. Enhanced gas sensitive property was achieved by visible light modulation. Light activated virtual sensor array was fabricated based on BP/Ti3C2Tx composite. Diagnosis of coronary heart disease was achieved with the help of machine learning.

Abstract Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

The structural heterogeneity and complexity of plant cell wall polysaccharides limit the release of phytonutrients in food processing, ultimately affecting the sensory quality, nutritional value, and shelf stability of products. Efficient enzymatic hydrolysis using plant cell wall polysaccharide-degrading enzymes (PCWPE) is a key step in overcoming the plant cell wall, a chemically complex structure composed mostly of polysaccharides, in food processing. PCWPE include cellulase, hemi-cellulase and pectinase, which specifically and efficiently hydrolyze glycosidic bonds in plant cell wall polysaccharides, significantly improving the sensory flavor and nutritional value of products, enhancing the stability of multiphase systems, and increasing the product yield. In recent years, PCWPE have been widely used in beverage processing, phytonutrient extraction, functional sugar preparation, and the processing of emerging sustainable plant-based food and thereby have become a research hotspot in the field of green food processing. This article summarizes the latest research on the mechanism of action of PCWPE, efficient enzymatic hydrolysis techniques and their application in the food industry, with a view to providing a reference for technological innovation in the field of high-quality plant-based food processing.

BackgroundOsimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib.Case summaryA 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up.ConclusionRegular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

Thermal stratification phenomena in SFRs and machine learning applications in nuclear system R&D have captured the community's attention. Existing methods, such as CFD, demand significant time and computational resources, hindering the timely prediction and management of thermal stratification in reactors. In response, this paper introduces a novel approach employing data-driven models for super real-time prediction of thermal stratification. Themodel aims to enhance the efficiency and speed of thermal stratification predictions. Refined flow field data were first obtained via CFD, revealing the transition mechanism between the dominant roles of inertial and buoyancy forces during thermal stratification formation. To select the optimal data-driven model, this paper employs the proper orthogonal decomposition (POD) method to evaluate three algorithms - k-nearest neighbor (KNN), classification and regression tree (CART), and least absolute shrinkage and selection operator (LASSO) - basedon temperature data from a temperature probe. Evaluation reveals that the POD-KNN model offers notable improvements in prediction speed while ensuring consistent accuracy, outperforming traditional numerical simulation methods for super real-time thermal stratification prediction.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P

Acquiring a comprehensive understanding of cropping patterns and their spatiotemporal distribution is crucial for sustainable agricultural development and ecological environment protection. However, the similarity of crop spectra and the diversity of ecosystem types hinder the accurate mapping of cropping patterns, especially in agricultural landscape regions. Hence, taking Xinghua County as study area, this article proposed a novel method for integrating multidimensional feature indices and phenological windows, named phenological window feature (PWF), to achieve efficient and accurate mapping of cropping patterns. In this study, we adopt a two-step approach. First, time-series curves of feature indices were constructed using Sentinel-1/2 satellite data to determine the phenological windows of different cropping patterns and construct PWF sets. Then, the ruleset threshold method (RTM) and random forest (RF) algorithms were used to map cropping patterns including wheat-rice, crayfish-rice, vegetable-rice, rice-rapeseed, rapeseed-vegetable, and year-round vegetables. The results indicate that the phenological windows extracted from the cropping patterns in the study area were 30–120, 90–135, and 200–270 days, respectively. The overall accuracies of RTM and RF, based on PWF, were 85.91% and 89.50%, respectively, and the kappa coefficients for RTM and RF were 0.831 and 0.872, respectively. In terms of classification performance, RF slightly outperformed RTM. The study demonstrates that PWF proposed in this article can be effectively utilized for mapping cropping patterns in complex agricultural landscape regions.

As more and more transmission lines need to pass through areas with heavy icing, the problem of transmission line faults caused by ice and snow disasters frequently occurs. Existing ice coverage monitoring methods have defects such as the use of a single monitoring type, low accuracy of monitoring results, and an inability to obtain ice coverage data over time. Therefore, this study proposes a new algorithm for detecting the icing status of transmission lines. The algorithm uses two-dimensional multifractal detrended fluctuation analysis (2D MF-DFA) to determine the optimal sliding-window size and wave function and accurately segment and extract local feature areas. Based on the local Hurst exponent (Lh(z)) and the power-law relationship between the fluctuation function and the scale at multiple continuous scales, the ice-covered area of a transmission conductor was accurately detected. By analyzing and calculating the key target pixels, the icing thickness was accurately measured, achieving accurate detection of the icing status of the transmission lines. The experimental results show that this method can accurately detect ice-covered areas and the icing thickness of transmission lines under various working conditions, providing a strong guarantee for the safe and reliable operation of transmission lines under severe weather conditions.

Climate change has significantly altered in the distribution of plant and animal species, potentially resulting in either species expansion or extinction. The genus Chimonanthus, an economically significant and endemic group in China, holds substantial medicinal and ornamental value; however, its wild resources are limited. There is a paucity of knowledge regarding the distribution characteristics of the genus Chimonanthus species and the critical ecological factors influencing habitat suitability. Utilizing species distribution data and environmental variables, we performed simulations and analyses to identify suitable habitats, evaluate the primary environmental factors influencing distribution, determine potential distribution areas and centroids, and predict changes in suitable areas under three future climate scenarios (SSP-126, SSP-245, SSP-585) employing MaxEnt and ArcGIS. These findings indicated that the Area Under Curve (AUC) values exceeded 0.97 for all five Chimonanthus species, suggesting that the model predictions are highly accurate. The primary environmental variables influencing the distribution of C. grammatus are temperature, particularly isothermality (BIO3), and the mean temperature of warmest quarter (BIO10). However, precipitation of warmest quarter (BIO18) was an important environmental factor limiting the distributions of C. praecox, C. nitens, C. salicifolius and C. zhejiangensis. In the current period, the area of habitat suitability for C. praecox is the largest, at 2,498,600 km2, while that for C. zhejiangensis is the smallest, at 700,400 km2. The five Chimonanthus species are distributed mainly in southern China under the current climate scenario and will migrate to higher latitudes under future climate scenarios. C. nitens had high niche overlap and range overlap with C. zhejiangensis and C. salicifolius, respectively. A similar situation occurs between C. zhejiangensis and C. salicifolius. These findings suggest that there may be strong interspecific competition among adjacent species. Our results indicate that the establishment of nature reserves at current distribution sites within optimal areas is crucial for the conservation of germplasm resources, particularly for C. grammatus and C. salicifolius. The data generated from this research can serve as a valuable reference for the selection of in situ conservation sites, the determination of appropriate planting locations, the scientific introduction of species, and the development of long-term conservation and management strategies for Chimonanthus.

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.

Chlorpyrifos is one of the most widely used broad-spectrum insecticides in agriculture. Given its potential toxicity and residue in food (e.g., tea), establishing a rapid and reliable method for the determination of chlorpyrifos residue is crucial. In this study, a strategy combining surface-enhanced Raman spectroscopy (SERS) and intelligent variable selection models for detecting chlorpyrifos residue in tea was established. First, gold nanostars were fabricated as a SERS sensor for measuring the SERS spectra. Second, the raw SERS spectra were preprocessed to facilitate the quantitative analysis. Third, a partial least squares model and four outstanding intelligent variable selection models, Monte Carlo-based uninformative variable elimination, competitive adaptive reweighted sampling, iteratively retaining informative variables, and variable iterative space shrinkage approach, were developed for detecting chlorpyrifos residue in a comparative study. The repeatability and reproducibility tests demonstrated the excellent stability of the proposed strategy. Furthermore, the sensitivity of the proposed strategy was assessed by estimating limit of detection values of the various models. Finally, two-tailed paired t-tests confirmed that the accuracy of the proposed strategy was equivalent to that of gas chromatography–mass spectrometry. Hence, the proposed method provides a promising strategy for detecting chlorpyrifos residue in tea.

Objective: To elucidate the chemical profile of Xanthocerais lignum’s extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. Methods: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum–effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. Results: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. Conclusions: This research clarifies Xanthocerais lignum’s pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.

Abstract Background Coronary artery ectasia is defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adjacent normal segment. The etiology of coronary artery ectasia is diverse, and rarely complicated with immunoglobulin G4-related disease (IgG4-related disease). A limited number of cases have been reported, with insidious onset, slow progression but poor prognosis. Case presentation we report a patient with coronary artery ectasia combined with IgG4-related disease. He has been diagnosed with IgG4-related disease 5 years after his first percutaneous coronary intervention (PCI). Despite routine treatment with steroids, he develops a large coronary aneurysm and eventually died. Conclusions It is suggested that a thorough evaluation should be performed when coronary artery ectasia is diagnosed. The factors such as manifestations of coronary artery thickening, typical imaging features, other aortas involvement, increased serum IgG4 level, etc. should be considered for early diagnosis of key etiologies.

Objective·To screen the human-mouse chimeric antibodies that neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and analyse the key amino acid site changes in their light chain.Methods·Antibody heavy chain gene-humanized mice were immunized with the spike protein of SARS-CoV-2. Enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay were performed to analyse the antibody titer in serum level. Flow cytometry was used to sort plasma cells and germinal center (GC) B cells from the mouse spleen and lymph nodes, and the proportions of different B cells were analysed. RNA was extracted to construct a mouse-origin antibody light chain gene library, which was paired with the knocked-in human-origin antibody heavy chain gene for antibody expression. ELISA was employed to screen for high-affinity chimeric antibodies. Amino acid changes in the light chain of high-affinity chimeric antibodies were analysed by comparing them with mouse-origin germline antibody light chain genes. Chimeric antibodies with single amino acid changes in the light chain were constructed and expressed, and their affinity and neutralization abilities were tested through ELISA and pseudovirus neutralization experiments. By comparing the affinity and neutralization abilities of the chimeric antibodies with or without single amino acid changes in the light chain, the key single amino acid change was analysed.Results·Compared to unimmunized mice, the immunized mice showed an increased titer of specific antibodies against SARS-CoV-2 on the serum level, along with an elevated proportion of plasma cells and GC B cells in the spleen and lymph nodes. ELISA showed that a high-affinity chimeric antibody was screened from GC B cells in the mouse spleen. The light chain of the antibody had a 76th serine-to-isoleucine substitution and a 98th phenylalanine deletion. Another ELISA showed that the chimeric antibody exhibited high affinity, the antibody without amino acid change on the light chain and the antibody with only the 98th phenylalanine deletion showed low affinity, and the antibody with only the 76th serine-to-isoleucine substitution demonstrated intermediate affinity between the chimeric antibody and the antibody without amino acid change on the light chain. Pseudovirus neutralization experiments revealed that the chimeric antibody had a half-maximal inhibitory concentration (IC50) of 0.995 ng/μL; the antibody with only the 76th serine-to-isoleucine substitution had an IC50 of 1.724 ng/μL, indicating a slight decrease in neutralization ability; the antibody with only the 98th phenylalanine deletion had an IC50 of 71.05 ng/μL; the antibody without amino acid change on the light chain had an IC50 of 42.06 ng/μL, suggesting weak neutralization ability.Conclusion·For the screened human-mouse chimeric antibodies that neutralize SARS-CoV-2 in this study, the key amino acid change determining the neutralization ability of the chimeric antibody is the 76th serine-to-isoleucine substitution.

Abstract Background Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1. Case presentation We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis. Conclusion A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.

Lipid peroxidation and redox imbalance are hallmarks of ferroptosis, an iron-dependent form of cell death. Growing evidence suggests that dysregulation in glycolipid metabolism and iron homeostasis substantially contribute to the development of hepatocellular carcinoma (HCC). However, there is still a lack of comprehensive understanding regarding the specific transcription factors that are capable of coordinating glycolipid and redox homeostasis to initiate the onset of ferroptosis. We discovered that overexpression of SOX8 leads to impaired mitochondria integrate, increased oxidative stress, and enhanced lipid peroxidation. These effects can be attributed to the inhibitory impact of SOX8 on de novo lipogenesis, glycolysis, the tricarboxylic acid cycle (TCA), and the pentose phosphate pathway (PPP). Additionally, upregulation of SOX8 results in reduced synthesis of NADPH, disturbance of redox homeostasis, disruption of mitochondrial structure, and impairment of the electron transport chain. Furthermore, the overexpression of SOX8 enhances the process of ferroptosis by upregulating the expression of genes associated with ferroptosis and elevating intracellular levels of ferrous ion. Importantly, the overexpressing of SOX8 has been observed to inhibit the proliferation of HCC in immunodeficient animal models. In conclusion, the findings suggest that SOX8 has the ability to alter glycolipid and iron metabolism of HCC cells, hence triggering the process of ferroptosis. The results of our study present a novel strategy for targeting ferroptosis in the therapy of HCC.

In the era of big data, data centers with high energy consumption, interconnectivity, and load flexibility have developed rapidly. However, due to data privacy issues, the traditional power-system operational reliability assessment (ORA) struggles to precisely consider the load flexibility of data centers, leading to inaccurate evaluation. To this end, this article proposes an ORA method considering the load flexibility of data centers via the energy consumption elastic space. By transforming the inner operation constraints of data centers into an equivalent elastic space, the ORA does not require any private data to complete the evaluation. Specifically, the energy consumption model of data centers is established to accurately describe the load flexibility. Then, based on multi-parametric programming techniques, the energy consumption elastic space of data centers is characterized by data centers’ power demand constraints, which do not involve privacy data, and no privacy concerns exist. Finally, the ORA model and the evaluation method based on the energy consumption elastic space can be constructed. With a lot of data center operation constraints being replaced by power demand constraints, the proposed method can complete an evaluation faster without accuracy loss. Its effectiveness is validated through simulations using the IEEE RTS 24-bus system and a provincial 661-bus system.

Background: The purpose of this study was to evaluate the ability of the systemic immune-inflammation index (SII) to predict the prevalence of stroke in the American population. Methods: A cross-sectional research study of 53,600 people was carried out utilizing information from the U.S. National Health and Nutrition Examination Survey (NHANES) database. Participants were divided into three groups based on the tertiles of their SII levels: SII-low, SII-median, and SII-high. Logistic regression analysis was used to investigate SII and the prevalence of stroke. Subgroup analyses, sensitivity analyses, and restricted cubic spline (RCS) analysis were also carried out. Results: A total of 2368 patients with stroke were found among the participants in this cross-sectional study. The high SII group had a substantially greater prevalence of stroke compared to the low SII group (odds ratio [OR] = 1.18, 95% confidence interval [CI] 1.01, 1.42). The risk of stroke decreased by 34% for every unit rise in log-transformed SII (OR 1.30, 95% CI 0.99, 1.70). A positive linear connection between SII levels and the prevalence of stroke was revealed using RCS analysis (p for non-linearity = 0.387). Conclusions: This cross-sectional study utilizing large-scale data from NHANES provides the first evidence of a significant association between higher SII levels and increased prevalence of stroke. These findings highlight the relevance of SII as a potential predictive marker for stroke.

Optical remote sensing satellites provide rapid access to regional topsoil salinization mapping. However, mapping topsoil salinization based on spectral reflectance is always affected by background material like vegetation cover, straw mulching and soil types. In light of these challenges, this study investigates the potential of image fusion, where images of original and bare soil pixels were combined, to minimize the impact of vegetation cover on topsoil salinity mapping. A case study was presented for the typical vegetation cover area using synchronized Sentinel-2 MSI image (named original image) and 255 ground-truth data collected in October 2020, aligning with periods of vegetation cover and salt return. Furthermore, to obtain novel bare soil pixels, multi-temporal Sentinel-2 MSI images were acquired during two distinct intervals: March to May and September to November, spanning the years from 2018 to 2021. The synthetic soil image (SYSI) was obtained by extracting bare soil pixels from multi-temporal images. Two images (original, SYSI) were fused with non-negative matrix factorization (NMF) method, named SYSIfused. Then, the stacking machine algorithm was used for soil salinity mapping under different soil types, with evaluating the impact of SYSIfused on the accuracy of soil salinity prediction. The results showed the SYSIfused outperformed the original image (the R2 of the best models increased by 0.054–0.242, RMSE and MAE decreased by 0.049–0.780 and 0.012–0.546, respectively). Based on the SYSIfused, the order of the effect of soil types was coastal bog solonchaks > alluvial soil > cinnamon soil > coral saline soil > overall samples, and their roles in improving the R2 of the model were 0.141, 0.085, 0.022, 0.012, respectively. Besides, stacking models with the SYSIfused provided the best prediction performances (R2 = 0.742, RMSE = 0.377, MAE = 0.362). This study introduces the concept of merging original images with SYSI, resulting in a significant improvement in the accuracy of soil salinity mapping in areas covered by vegetation.

Abstract Introduction : Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied. Methods : In this study, we included 12 PD patients (6 male and 6 female) who underwent STN‐DBS surgery and had both 18F‐FDG and 11C‐CFT PET/CT imaging before and 1 year after the surgery. We used paired t‐tests to identify changes in cerebral metabolism and calculated PD‐related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of 11C‐CFT in the striatum using striatal‐to‐occipital ratios (SORs). Results : One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p

Objective: optimizing the extraction process of methylated catechin from Zijuan tea. Methods: Using acid ethanol as extraction solvent, based on three single factor experiments, the extraction time, extraction temperature and liquid-solid ratio were used to investigate the interaction of the above three factors on the extraction rate of methylated catechin from Zijuan tea. Results: The optimum extraction conditions were as follows: extraction time 100 min, extraction temperature 75 ℃, solid-liquid ratio（m Zijuan tea∶VSolvent） 1∶74 （g/mL）; under these conditions, the mass concentration of methylated catechin in the extract could reach 26.7 mg/g, and the relative error with the verification value was 1.48%. Conclusion: HPLC and response surface methods were used to optimize the extraction process of methylated catechins in Zijuan tea. The process is simple and the verification results are reasonable.

Abstract Background Inflammation plays a critical role in acute myocardial infarction (AMI). Recent studies have shown the value of hematologic indicators in MI risk stratification and prognostic assessment. However, the association between lymphocyte-to-monocyte ratio (LMR) and the long-term mortality of critically ill MI patients remains unclear. Methods Clinical data were extracted from the Medical Information Mart for Intensive Care III database. Patients diagnosed with AMI on admission in the intensive care units were include. The optimal cutoff value of LMR was determined by X-tile software. The Cox proportional hazard model was applied for the identification of independent prognostic factors of 1-year mortality and survival curves were estimated using the Kaplan–Meier method. In order to reduce selection bias, a 1:1 propensity score matching (PSM) method was performed. Results A total of 1517 AMI patients were included in this study. The cutoff value for 1-year mortality of LMR determined by X-Tile software was 3.00. A total of 534 pairs of patients were matched after PSM. Multivariate analysis (HR = 1.369, 95%CI 1.110–1.687, P = 0.003) and PSM subgroups (HR = 1.299, 95%CI 1.032–1.634, P = 0.026) showed that 1-year mortality was significantly higher in patients with LMR

Antibodies are important immune molecules that are elicited by B cells to protect our bodies during viral infections or vaccinations. In humans, the antibody repertoire is diversified by programmed DNA lesion processes to ensure specific and high affinity binding to various antigens. Broadly neutralizing antibodies (bnAbs) are antibodies that have strong neutralizing activities against different variants of a virus. bnAbs such as anti-HIV bnAbs often have special characteristics including insertions and deletions, long complementarity determining region 3 (CDR3), and high frequencies of mutations, often at improbable sites of the variable regions. These unique features are rare mutational outcomes that are acquired during antibody diversification processes. In this review, we will discuss possible mechanisms that generate these rare antibody mutational outcomes. The understanding of the mechanisms that generate these rare mutational outcomes during antibody diversification will have implications in vaccine design strategies to elicit bnAbs.

PurposeThe study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves.MethodsA retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. ResultsA total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p

Abstract Background Berberine (BBR) is an isoquinoline alkaloid found in the Berberis species. It was found to have protected effects in cardiovascular diseases. Here, we investigated the effect the regulatory function of long noncoding RNAs (lncRNAs) during the treatment of stable coronary heart disease (CHD) using BBR. We performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between whole blood samples from 5 patients with stable CHD taking BBR and 5 no BBR volunteers. DE lncRNAs and mRNAs were validated by quantitative real-time PCR. Results A total of 1703 DE lncRNAs and 912 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated DE mRNAs might be associated with mammalian target of rapamycin and mitogen-activated protein kinase pathway. These pathways may be involved in the healing process after CHD. To study the relationship between mRNAs encoding transcription factors (DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene) and CHD related de mRNAs, we performed protein and protein interaction analysis on their corresponding proteins. AKT and apoptosis pathway were significant enriched in protein and protein interaction network. BBR may affect downstream apoptosis pathways through DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene. Growth arrest-specific transcript 5 might regulate CHD-related mRNAs through competing endogenous RNA mechanism and may be the downstream target gene regulated by BBR. Verified by the quantitative real-time PCR, we identified 8 DE lncRNAs that may relate to CHD. We performed coding and non-coding co-expression and competing endogenous RNA mechanism analysis of these 8 DE lncRNAs and CHD-related DE mRNA, and predicted their subcellular localization and N6-methyladenosine modification sites. Conclusion Our research found that BBR may affect mammalian target of rapamycin, mitogen-activated protein kinase, apoptosis pathway and growth arrest-specific transcript 5 in the process of CHD. These pathways may be involved in the healing process after CHD. Our research might provide novel insights for functional research of BBR.

Abstract Background Stomach adenocarcinoma (STAD) is a common malignant tumor in the world and its prognosis is poor, miRNA plays a role mainly by influencing the expression of mRNAs, and participates in the occurrence and development of tumors. However, reliable miRNA prognostic models for stomach adenocarcinoma remain to be identified. Results Using the data from the Cancer Genome Atlas (TCGA), a prognostic model of stomach adenocarcinoma was established including tumor stage and expression levels of 4 miRNAs (hsa-miR-379-3p, hsa-miR-2681-3p, hsa-miR-6499-5p and hsa-miR-6807-3p). A total of 50 ultimate target genes of these miRNAs were obtained through prediction. Enrichment analysis revealed that target genes were mainly concentrated in neural function and TGF-β and FoxO signaling pathways. Survival analysis showed that three model miRNAs (hsa-miR-379-3p, hsa-miR-2681-3p and hsa-miR-6807-3p) and five final target genes (DLC1, LRFN5, NOVA1, POU3F2 and PRICKLE2) were associated with the patient's overall survival outcome. Conclusions We used bioinformatics methods to screen new prognostic miRNA markers from TCGA and established a prognostic model of STAD, so as to provide a basis for the diagnosis, prognosis, and treatment of STAD in the future.

ObjectiveEpithelial-to-mesenchymal transition (EMT) is tightly associated with the invasion and metastasis of pancreatic cancer with rapid progression and poor prognosis. Notably, gene alternative splicing (AS) event plays a critical role in regulating the progression of pancreatic cancer. Therefore, this study aims to identify the EMT-related AS event in pancreatic cancer.MethodsThe EMT-related gene sets, transcriptomes, and matched clinical data were obtained from the MSigDB, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Key gene AS events associated with liver metastasis were identified by prognostic analysis, gene set variation analysis (GSVA), and correlation analysis in pancreatic cancer. The cell line and organoid model was constructed to evaluate these key gene AS events in regulating pancreatic cancer in vitro. Furthermore, we established an EMT-related gene set consisting of 13 genes by prognostic analysis, the role of which was validated in two other databases. Finally, the human pancreatic cancer tissue and organoid model was used to evaluate the correlation between the enrichment of this gene set and liver metastasis.ResultsPrognostic analysis and correlation analysis revealed that eight AS events were closely associated with the prognosis of pancreatic cancer. Furthermore, the expression of TMC7 and CHECK1 AS events was increased in the metastatic lesions of the human tissue and organoid model. Additionally, the knockdown of exon 17 of TMC7 significantly inhibited the proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments. Finally, the expression of exon 17 of TMC17 exhibited a significant correlation with the poor prognosis in pancreatic ductal adenocarcinoma (PDAC).ConclusionThe AS events of TMC7 and CHECK1 were associated with liver metastasis in pancreatic cancer. Moreover, exon 17 of TMC7 could be a potential therapeutic target in pancreatic cancer.

ObjectiveThis study aimed to investigate the application value of multi-parametric magnetic resonance imaging (MRI) in the diagnosis of iron deposition in the substantia nigra dense zone in Parkinson's disease (PD) and to evaluate the diagnostic value of the correlation among multi-parametric imaging indicators, clinical stage, and disease duration.Materials and methodsThirty-six patients with clinically confirmed PD and 36 healthy controls were enrolled. The disease course was recorded, and PD severity was graded using the Hoehn–Yahr (H–Y) scale. All subjects underwent magnetic sensitivity weighted imaging (SWI), neuromelanin magnetic resonance imaging (NM-MRI), and a T2*mapping sequence. Based on the fusion of the NM-MRI and SWI amplitude maps, phase maps, and T2*MAPPING value maps, NM-MRI was used to delineate the dense zone of the substantia nigra, which was divided into three sub-regions: upper, middle, and lower. In this way, the amplitude, phase, and R2* values of each sub-region and the average value of the sum of the three sub-regions were obtained simultaneously in the SWI amplitude, phase, and T2*MAPPING maps. The multi-parameter imaging indices were compared between the two groups, and the correlation between them and clinical indices was evaluated in the PD group.ResultsThe upper (amplitude, phase value, R2* value), middle, and lower (amplitude) right substantia nigra compact zones were significantly different between the PD and control groups. The upper (phase value, R2* value) and middle (amplitude) areas of the left substantia nigra compact zone were also significantly different between the two groups (all P < 0.05). The mean values (amplitude, phase value, R2* value) of the right substantia nigra densification zone and the mean values (phase value) of the left substantia nigra densification zone were also significantly different (all P < 0.05). Amplitudes in the middle and lower parts of the right substantia nigra dense zone were negatively correlated with the H–Y grade (middle: r = −0.475, P = 0.003; lower: r = −0.331, P = 0.049). Amplitudes of the middle and lower parts of the dense zone of the left substantia nigra were negatively correlated with the H–Y grade (middle: r = −0.342, P = 0.041; lower: r = −0.399, P = 0.016). The average amplitude of the right substantia nigra compact zone was negatively correlated with the H–Y grade (r = −0.367, P = 0.027). The average R2* value of the compact zone of the left substantia nigra was positively correlated with the H–Y grade (r = 0.345, P = 0.040).ConclusionMultiparametric MRI sequence examination has application value in the evaluation of iron deposition in the dense zone of the substantia nigra in PD. Combined with NM-MRI, fusion analysis is beneficial for accurately locating the substantia nigra compact zone and quantitatively analyzing the iron deposition in different sub-regions. Quantitative iron deposition in the middle and lower parts of the substantia nigra dense zone may become an imaging biological indicator for early diagnosis, severity evaluation, and follow-up evaluation of PD and is thus conducive for clinical diagnosis and treatment evaluation.

In this study, the mechanism and predictability of a remote typhoon heavy rainfall in eastern Zhejiang Province are investigated by ensemble anomaly forecasting, with ECMWF reanalysis data, ECMWF ensemble prediction data, and automatic weather station precipitation data. Results show that: (1) Under the intrusion of cold air from the north side of the typhoon inverse which existed for a long time, it caused frontal formation in the coastal area of Zhejiang, and induced a low pressure circulation at the top of the inverse trough, was the main reason for the heavy rainfall in the northeast of Zhejiang. (2) The ensemble forecast with 36-hour prediction valid shows that precipitable water vapor, south wind component on 850 hPa, water vapor flux on 925 hPa and divergence of 200 hPa all exceed 3~4 standard deviations of climate average, and the probability of standard deviation exceeding 3 reaches 70%~90%. These factors indicate that great dynamic condition and abundant water vapor exist along the coast of Zhejiang. Strong anomalous signals predict high probability of an extreme heavy rainfall event. (3) With the extension of the forecast lead time, the anomalous probability of each physical quantity is significantly reduced. Therefore, the threshold of anomalous probability should be reduced for the early warning of extreme weather. (4) The EFIs (Extreme Forecast Index) with different forecast lead time have good prediction results for 95% and 99% percentile precipitation events, and it can provide extreme precipitation signals 3~4 days earlier than deterministic forecasts. The information for extreme rainfall events provided by ensemble prediction EFI index is more reliable and stable than deterministic forecast, and has higher reference value in decision-making services. (5) Ensemble anomaly forecasting method quantitatively measures the abnormal probability of synoptic scale pattern and physical quantities. EFI shows advantage in longer-time scale forecast. The combination of these two forecast methods could provide more comprehensive signal for extreme weather event.

Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.

Considered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying mechanisms. In this study, synovial tissue samples were collected from RA patients, and RA-fibroblast-like synoviocytes (FLSs) were subsequently isolated. The expression levels of PLD1 and pathway-related proteins were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting or immunohistochemistry (IHC). Upon shPLD1 treatment, cell viability, proliferation, migration, invasion, and the level of inflammation-related factors were measured by Cell Counting Kit-8 (CCK-8), Edu, wound healing, Transwell and enzyme-linked immunosorbent assay (ELISA). Furthermore, C-reactive protein (CRP), rheumatoid factor (RF), arthritis score and synovial tissue lesions were assessed by collecting the blood or tissues from collagen induced arthritis (CIA) model rats. Our results showed that PLD1 level was increased in RA synovial tissues. Cell viability, proliferation, migration, invasion, and the level of inflammatory factors were reduced upon PLD1 knockdown in RA-FLSs. Moreover, p-IκBα/IκBα, β-catenin, p-IKKβ/IKKβ and TCF-4 were inhibited under PLD1 knockdown treatment. PLD1 knockdown alleviated the collagen-induced addition of arthritis score, CRP and RF, as well as the filling of inflammatory cells and proliferation of synovium in CIA model rat. To sum up, knockdown of PLD1 could reduce RA-FLSs metastasis as well as inflammatory response by modulating the activity of NF-κB and Wnt/β-catenin pathways.

This research serves to advance the development of engineering computational fluid dynamics (CFD) computing efficiency for the analysis of pressurized water reactor (PWR) core using rod-type fuel assemblies with mixing vanes (one kind of typical PWR core). In this research, a CFD scheme based on the reconstruction of the initial fine flow field (RIF CFD scheme) is proposed and analyzed. The RIF scheme is based on the quantitative regulation of flow velocities in the rod-type PWR core and the principle that the CFD computing efficiency can be improved greatly by a perfect initialization. In this paper, it is discovered that the RIF scheme can significantly improve the computing efficiency of the CFD computation for the rod-type PWR core. Furthermore, the RIF scheme also can reduce the computing resources needed for effective data storage of the large fluid domain in a rod-type PWR core. Moreover, a flow-ranking RIF CFD scheme is also designed based on the ranking of the flow rate, which enhances the utilization of the flow field with a closed flow rate to reconstruct the fine flow field. The flow-ranking RIF CFD scheme also proved to be very effective in improving the CFD efficiency for the rod-type PWR core.

Summary: The role of tripartite motif (TRIM) 38, a ubiquitin E3 ligase regulating various pathophysiological processes, in cardiac fibrosis remains unclear. Here, a model of angiotensin II and myocardial infarction (MI)-induced fibrosis was established to explore its role in cardiac fibrosis and its underlying mechanisms. Cardiac fibrosis in the mouse MI model was mitigated by TRIM38 overexpression, but aggravated by its depletion. Consistently, in vitro overexpression or knockdown of TRIM38 ameliorated or aggravated the proliferation and secretion of cardiac fibroblasts (CFs) exposed to fibrotic stimulation, respectively. Mechanistically, TRIM38 suppressed cardiac fibrosis progression by attenuating TAK1/MAPK signaling. Inhibiting TAK1/MAPK signaling with a pharmacological inhibitor greatly reversed the effects of TRIM38 knockdown on CF secretion. Specifically, TRIM38 interacted with and “targeted” TAB2 and TAB3 for degradation, subsequently inhibiting TAK1 phosphorylation and negatively regulating MAPK signaling. These findings can help develop therapeutic strategies to treat and prevent cardiac fibrosis.

The precipitation Extreme Forecast Index (EFI) derived from ECMWF global ensemble prediction system (EPS) from June 2016 to May 2017 is applied to evaluate the statistical relationship between the EFI and the severe precipitation as well as the climatic precipitation percentile in Zhejiang. Results show that there is an obvious positive correlation between the EFI and the observed precipitation in Zhejiang. With the increase of the EFI threshold, the frequency of rainstorm increases at first and then decreases, and the probability of rainstorm increases with the increase of EFI threshold. With the increase of the EFI, the frequency of rainstorm increases at first and then decreases, while the probability of rainstorm increases with the increase of the EFI. Considering the TS and BS scores comprehensively, the threshold of the EFI decreases with the increase of forecast time length and increase with the increase of precipitation. There is a significant positive correlation between the EFI value and the climatic percentile of precipitation. The greater the EFI is, the higher the percentile is. Thus, the precipitation amount can be estimated according to the corresponding climatic percentile of the observed precipitation.

Synchronization is the key part to ensure the high performance of grid-connected systems. Phase-locked loop (PLL) is one of the most popular synchronizations due to its simple implementation and robustness under certain grid variations. Particularly, in single-phase applications, PLL based on second-order generalized integrator (SOGI-PLL) is widely used because of its simple structure, certain filtering ability and frequency adaptability. The sensitivity of SOGI-PLL to the dc offset and low-order harmonics has been studied a lot in the literature and many solutions have been proposed. However, as more and more power electronic devices are integrated into the power grid recently, the grid condition becomes more complex. As a result, the nonlinear loop coupling phenomenon of SOGI-PLL is more severe and obvious and thus the performance of SOGI-PLL is degraded a lot, especially under the conditions of grid frequency variations and weak grid. A popular method is to use the frequency-fixed SOGI-PLL (FFSOGI-PLL) while how to eliminate the estimation error under frequency variations remain an important task. Though some scattered methods have been proposed, a simple yet effective strategy is still missing. Besides, it has been shown that the system stability margin will be reduced due to the negative-resistance behavior of PLL. However, the models derived in the current documents cannot accurately reveal the instabilities caused by the standard SOGI-PLL for missing the dynamics of the frequency feedback loop. Moreover, the PLL parameters are usually designed according to the PLL bandwidth to guarantee system stability under a weak grid. How to optimize the parameters is still unclear. In view of this, this article further summarizes and reviews the existing achievements of single-phase SOGI-PLL, and points out the problems to be solved and the development direction to improve the SOGI-PLL under more complex and non-ideal grid conditions.

Abstract The Mufushan-Jiaoshan fault (MJF) is a hidden active fault located on the north side of the Ningzhen Mountain Range and developed along the Yangtze River in Zhenjiang area, China. In this paper, the structure of MJF is detected and studied using group-velocity ambient noise tomography. In the study area (18 km × 25 km), 47 short-period seismic stations were deployed with the average station spacing of about 3 km and 24 days (from 27 February to 22 March 2019) of continuous ambient-noise recordings were collected. And 510 group velocity dispersion curves in the period band 0.5–5 s were extracted using the vertical component data. And then the three-dimensional shear-wave velocity structure was inverted using group dispersion data by the direct surface-wave tomographic method. Our results are consistent with the geological background of the study area, showing that in the depth range of 0.6–1.5 km, the north side of MJF presents a relatively high velocity, and the south side presents a distribution pattern of high and low velocity. While in the depth range of 1.5–2.0 km, the shear-wave velocity (Vs) model is relatively simple with relatively low velocity on the north side and relatively high velocity on the south side. And the gradient zone of Vs may be the location of the main fracture surface of MJF. The good correspondence between the Vs model and the fault structure indicates that the ambient noise tomography method can be used as an effective method for detecting hidden faults in urban environments.

Phosphorus-31 nuclear-spin entanglements within Ca9(PO4)6 molecules (Posner molecules) have been proposed to be central for neural processing. However, this has yet to be proven experimentally. Relatedly, increasing calcium ion concentration in the cerebrospinal fluid has been proposed to enhance consciousness by accelerating Posner molecules' creation. A dependence on calcium isotope is also expected. Here we test these predictions experimentally by measuring the loss of righting reflex ED50 for mice to sevoflurane - an increase in loss of righting reflex ED50 indicates a higher level of consciousness and vice versa. Our mice's findings demonstrate that intracerebroventricular injection of EGTA enhances the sevoflurane-induced loss of righting reflex ED50 while injecting calcium-40 chloride or calcium-43 chloride causes an opposite effect. Further, the identical effects of calcium-40 and calcium-43 indicate an absence of calcium isotope dependence. Here, our findings disprove conventional proposals that calcium ion concentration correlates with consciousness.

Abstract Aims Cardiac complications are common and associated with mortality in critically ill patients with COVID‐19; however, the diagnostic and prognostic implications of critical care echocardiography (CCE) have not been studied. Methods and results A cohort of 43 patients with COVID‐19 who were in the intensive care unit (ICU) underwent bedside CCE during their disease course. Demographic, clinical, and survival data were collected. The echocardiographic analyses revealed high frequencies of pericardial effusion (90.7%), increased left ventricular mass index (60.5%), elevated relative wall thickness (76.7%), and reduced left ventricular stroke volume index (LVSVi; 53.5%) and cardiac index (51.2%). Twenty‐two (51.2%) patients died in the ICU. In multivariate Cox regression, the strongest predictor of in‐ICU death was decreased cardiac index [hazard ratio (HR), 0.67, 95% confidence interval (CI), 0.45–0.98; P = 0.041], after adjusting for male sex, shock status, high‐sensitivity cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide. Negative associations with mortality were observed for LVSVi (HR, 0.91, 95% CI 0.85–0.96; P = 0.002), tricuspid annular plane systolic excursion (HR, 0.74, 95% CI 0.64–0.84; P

For inverters, a phase-locked loop (PLL) is usually needed for the grid synchronization. Typically, for the single-phase inverters, the orthogonal-signal-generators based PLLs (e.g., delay-based PLL) can be used. However, if the grid at the point of common coupling (PCC) exhibits a large grid impedance, the inverter may not work well or even be unstable. In order to work satisfactorily in the very weak grid, this study aims to formulate a robust PLL. At first, by modeling the inverter output impedance and considering the frequency coupling effect, the stability of the typical delay-based PLL has been analyzed and the reason for the performance degradation has been explained. Then, based on analyzing the differences of PLL blocks under different PCC conditions, the robust PLL with the grid current feedforward is discussed. Compared with the typical PLL, the improvement of the system behaviors in the weak grid cases is mainly attributed to the extra term on the numerator of output impedance, which is introduced by the current feedforward of the proposed PLL. The selection of control parameters has been emphasized for maintaining the high robustness. At last, selected comparative waveforms have verified that the single-phase inverter can perform well even with the large grid impedance, without the grid impedance estimation.

Fibrosis is an outcome of tissue repair after different types of injuries. The homeostasis of extracellular matrix is broken, and excessive deposition occurs, affecting the normal function of tissues and organs, which could become prostrated in serious cases.Finding a suitable target to regulate the repair process and reduce the damage caused by fibrosis is a hot research topic at present. The TRIM family is number of one of the E3 ubiquitin ligase subfamilies and participates in various biological processes including intracellular signal transduction, apoptosis, autophagy, and immunity by regulating the ubiquitination of target proteins. For the past few years, the important role of TRIM in the occurrence and development of fibrosis has been gradually revealed. In this review, we focus on the recent emerging topics on TRIM proteins in the regulation of fibrosis, fibrosis-related cytokines and pathways.

In a steam generator, the heat transfer tubes are supported by the contact with support plates and anti-vibration bars. The two-phase flow flows over the tubes and causes a vibration when operating. In fatigue analysis, the heat transfer tube is simplified to a beam model, and the contacts with the support plates and the anti-vibration bars are simplified as simple-supported boundary conditions. This linear simplification improves the computational efficiency but cannot simulate the actual situation of the contact area. In consideration of this situation, in the actual analysis, a downwards modified S–N fatigue curve is used to envelop the fretting. For different materials and contact pressure, this modification needs to be obtained through experimental and computational analysis. In this paper, the effect of fretting on fatigue performance of heat transfer tube material 690 alloy is discussed by means of high cycle fretting fatigue test of tube specimen in room temperature air, low cycle fretting fatigue test of sheet specimen in high temperature water environment, and SWT (Smith–Watson–Topper) fretting fatigue predicting simulation, and the conservatism of design fatigue curve is discussed. It is shown that, in range of low cycle and high cycle, the fatigue strength is lower than the mean curve, but it can still be enveloped by the design curve of ASME (the American Society of Mechanical Engineers). However, under the condition of ultra-high cycle, the design curve of ASME can no longer envelop the effect of fretting on fatigue performance, so a further downward modification is necessary to ensure the safety of design.

The geopolymerization of aluminosilicate materials in alkaline environments is a complex physicochemical process that greatly influences the microstructure and engineering performances. This work aims to reveal the geopolymerization process of metakaolin-based geopolymer (MKG) in the first 5 d. Physicochemical characteristics of different evolution stages are disposed of in chronological order. The evolutions of electrical resistivity, dehydration process, volume deformation, and ionic concentration are comprehensively analyzed. Results show that chemical dissolution produces large dismantled fragments rather than small free monomers. The formation of a solid matrix follows the “spatial filling rule”, which means that gels grow by locking swelling fragments to form a framework, then densely filling residual space. Based on chemical models, early geopolymerization of MKG can be divided into six stages from the physicochemical perspective as dismantling, locking fixation, free filling, limited filling, second dissolution, and local mending. Those findings expand the understanding of the phase evolution of the early geopolymerization process; thus, the microstructure of MKG can be better manipulated, and its engineering performances can be improved.

Staphylococcus aureus is one of the main pathogens causing mastitis in dairy animals worldwide. It is an important opportunistic pathogen of raw milk, and the enterotoxin causes significant food poisoning. Monitoring the antibiotic resistance of S. aureus in raw milk is helpful for a risk assessment of S. aureus. In this study, 62 strains (43.1%) of S. aureus were isolated from 144 retail raw milk samples of different varieties from four regions in northern Xinjiang, China. Among them, the isolation rates at Shihezi, Hami, Altay, and Tacheng were 58.1% (54/93), 12.9% (4/31), 18.2% (2/11), and 22.2% (2/9), respectively. The isolation rate of positive strains in cow milk samples was the highest (61.7%, 37/60), followed by camel milk (35.9%, 23/64), and horse milk (10.0%, 2/20). The results of the classical virulence genes test showed that 12.9% (8/62) of the isolates carried at least one virulence gene. The main genotype was see (6.5%, 4/62), followed by sea+sec (3.2%, 2/62), sea (1.6%, 1/62), and sec (1.6%, 1/62). The analysis of 13 resistance genes and the susceptibility to 12 different antibiotics of 62 isolates showed that 80.6% (50/62) of the strains were resistant to at least one antibiotic, and 46.8% (29/62) were resistant to three or more antibiotics. The isolated strains had the highest resistance rate to penicillin (72.6%, 45/62), and 25.8% (16/62) of the isolates carried the blaZ resistance gene. In addition, 32 strains (51.6%, 32/62) of methicillin-resistant S. aureus were detected. All isolates had the ability to form biofilms. The pulsed-field gel electrophoresis results showed that the 47 isolates revealed 13 major pulsotypes (P1–P13) and 26 subtypes with 80% similarity, indicating the overall genetic diversity in the distribution area and sources of the samples. These findings indicate that S. aureus causes serious pollution of raw milk in northern Xinjiang, which has a negative effect on public health. Therefore, control measures and continuous monitoring should be undertaken to ensure the quality and safety of raw milk.

Spinal cord injury (SCI) is a destructive and complex disorder of the central nervous system (CNS) for which there is no clinical treatment. Blood-spinal cord barrier (BSCB) rupture is a critical event in SCI that aggravates nerve injury. Therefore, maintaining the integrity of the BSCB may be a potential method to treat SCI. Here, we showed that patchouli alcohol (PA) exerts protective effects against SCI. We discovered that PA significantly prevented hyperpermeability of the BSCB by reducing the loss of tight junctions (TJs) and endothelial cells. PA also suppressed endoplasmic reticulum stress and apoptosis in vitro. Furthermore, in a rat model of SCI, PA effectively improved neurological deficits. Overall, these results prove that PA exerts neuroprotective effects by maintaining BSCB integrity and thus be a promising candidate for SCI treatment.

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.

Tumor microenvironment comprises of a variety of cell types, which is quite complex and involved in chemotherapy and immune checkpoint blockage resistance. In order to explore the mechanisms involved in tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC), we first constructed an immunity-related 18-gene signature using The Cancer Genome Atlas (TCGA) PDAC project data. Then we applied the 18-gene signature to divide PDAC patients into low score and high score groups. Patients in high score group showed inferior prognosis, which was validated in another four independent cohorts, including Ruijin cohort. High score group showed significant enrichment of pathways involved in cell division and cell cycle especially in G1/S phase transition. In high score group, IHC analysis revealed higher levels of the proliferative indexes of Ki67 and PCNA than that in low score group. Prognostic analysis confirmed that patients in high score group could benefit from the gemcitabine-based adjuvant chemotherapy. In low score group, the programmed cell death 1 ligand 1(PD-L1) (+) cases showed worse prognosis but higher T cell infiltration than PD-L1(−) cases. Our immunity-related 18-gene signature could effectively predict PDAC prognosis, and it might be a practical predictive tool to identify PDAC subtype benefitting from gemcitabine-based adjuvant chemotherapy or potentially responding to PD1/PD-L1 blockade therapy.