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Increasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cells (hESCs) treated with extractable organic matters (EOM) from PM2.5 concentrations above 100 μg/mL exhibited reduced viability. While EOM within non-cytotoxicity concentrations did not affect the expression levels of pluripotency genes, it did enhance cellular proliferation, as indicated by increased Edu incorporation and the upregulation of cell cycle genes (Cdk2, Mdm2). Additionally, EOM significantly influenced the transcriptome patterns in hESCs. Notably, the differentially expressed genes were found to be significantly enriched in processes such as extracellular matrix organization, cell–cell junction organization, chromatin organization, and DNA methylation. Furthermore, we observed whole genomic-wide DNA methylation changes. Through a cross-analysis of changes in DNA methylation and mRNA expression, we identified an enrichment of terms related to the VEGFR signaling pathway and extracellular matrix. The gene signal transduction networks revealed that crucial hubs were implicated in cell growth and division. In conclusion, our findings demonstrate that PM2.5 induce significant alterations in transcriptome and DNA methylome in hESCs, leading to aberrant cell proliferation. This research provides novel insights into the molecular mechanisms underlying the developmental toxicity of PM2.5.

Abstract The objective of this study was to investigate the prevalence of preoperative deep venous thrombosis (DVT) in the pelvic cavity and lower extremities following pelvic and acetabular fractures and to identify the risk factors of the occurrence of DVT. Duplex ultrasound (DUS) screening and blood tests were conducted in patients admitted from June 2012 to December 2020 for surgical treatment of pelvic and acetabular fractures. Univariate analyses were performed on data of demographics, comorbidities, time from injury to surgery, injury mechanism, accompanied injury, and laboratory results. The optimal cutoff values of continuous variables with statistical significance were obtained by using the receiver operating characteristic (ROC) curve. A multivariate logistic regression analysis was then employed to examine the independent values in terms of predicting preoperative DVT. A total of 607 patients with pelvic and acetabular fractures were included, among whom 82 (13.5%) patients sustained preoperative DVTs. Specifically, 31.7% (26/82) were diagnosed with proximal DVTs. Fifty-two (63.4%) patients had DVT within 7 days after injury, and 67 (81.7%) patients within 10 days. The multivariate logistic regression analysis identified 6 factors independently associated with the presence of preoperative DVT, including age > 46 years (odds ratio [OR] = 2.94), BMI > 26.73 kg/m2 (OR = 3.91), time from injury to surgery > 9 days (OR = 5.39), associated injury (OR = 7.85), ALB 3.095 g/L (OR = 3.34). Despite the modern prophylactic regimen, the preoperative DVT in patients with pelvic and acetabular fractures still draws the attention of orthopaedic surgeons. Better understanding these risk factors can help surgeons refine the risk stratification profile and perform early interdisciplinary management for patients at high risk of DVT.

Abstract Background The decoction of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) has been reported as a potential antitumor agent for colorectal cancer (CRC) in experimental and clinical studies, but its underlying mechanism is still unclear. Methods The current research aims to explore the potential of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction (AR decoction) in the treatment of CRC and explore the underlying mechanism. SW620 cells were transient transfection to overexpress or knock down wnt 5 or β-Catenin. Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) -containing serum (AR-CS) was used to interfere with SW620 cells. Additional AR-CS, Wnt5 inhibitor (IWP-4), and β-Catenin inhibitor (JW55) were used to intervene in SW620 cells. Furthermore, subcutaneously injection of SW620 cells into the right flank of nude mice replicated xenograft mice, which were treated with AR decoction for 21 days. Results AR-CS significantly reduced the mRNA and protein expression levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in SW620 cells, while inhibiting the proliferation and migration of SW620 cells. In cells overexpressing Wnt5 or β-Catenin, these effects of AR-CS were significantly suppressed. On the contrary, the inhibitory effect of AR-CS on the mRNA and protein levels of ARF6 and N-Cadherin and cell proliferation and migration of SW620 was enhanced, when Wnt5 or β-Catenin were knocked down or suppressed by the inhibitors. Moreover, in the mouse model of xenograft tumors, AR decoction not only reduced the tumor volume and inhibited the mRNA levels and protein levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in the tumor, but also inhibit the protein levels of LRP5, LRP6, TCF-4, and LEF1.The histopathology of mice also showed increased apoptosis in tumor tissues, and AR decoction treatment did not cause pathological damage to the kidney and liver. Conclusions Our results provide evidence that AR decoction inhibits Wnt5/β-catenin signaling and inhibits the development of CRC, which is a promising traditional medicine in the clinical treatment of CRC.

Abstract Background The exchange of knowledge between statisticians developing new methodology and clinicians, reviewers or authors applying them is fundamental. This is specifically true for clinical trials with time-to-event endpoints. Thereby, one of the most commonly arising questions is that of equal survival distributions in two-armed trial. The log-rank test is still the gold-standard to infer this question. However, in case of non-proportional hazards, its power can become poor and multiple extensions have been developed to overcome this issue. We aim to facilitate the choice of a test for the detection of survival differences in the case of crossing hazards. Methods We restricted the review to the most recent two-armed clinical oncology trials with crossing survival curves. Each data set was reconstructed using a state-of-the-art reconstruction algorithm. To ensure reproduction quality, only publications with published number at risk at multiple time points, sufficient printing quality and a non-informative censoring pattern were included. This article depicts the p-values of the log-rank and Peto-Peto test as references and compares them with nine different tests developed for detection of survival differences in the presence of non-proportional or crossing hazards. Results We reviewed 1400 recent phase III clinical oncology trials and selected fifteen studies that met our eligibility criteria for data reconstruction. After including further three individual patient data sets, for nine out of eighteen studies significant differences in survival were found using the investigated tests. An important point that reviewers should pay attention to is that 28% of the studies with published survival curves did not report the number at risk. This makes reconstruction and plausibility checks almost impossible. Conclusions The evaluation shows that inference methods constructed to detect differences in survival in presence of non-proportional hazards are beneficial and help to provide guidance in choosing a sensible alternative to the standard log-rank test.

Telomerase, an RNA-dependent DNA polymerase synthesizing telomeric TTAGGG sequences, is primarily silent in normal human urothelial cells (NHUCs), but widely activated in urothelial cell-derived carcinomas or urothelial carcinomas (UCs) including UC of the bladder (UCB) and upper track UC (UTUC). Telomerase activation for telomere maintenance is required for the UC development and progression, and the key underlying mechanism is the transcriptional de-repression of the telomerase reverse transcriptase (TERT), a gene encoding the rate-limiting, telomerase catalytic component. Recent mechanistic explorations have revealed important roles for TERT promoter mutations and aberrant methylation in activation of TERT transcription and telomerase in UCs. Moreover, these TERT-featured genomic and epigenetic alterations have been evaluated for their usefulness in non-invasive UC diagnostics, recurrence monitoring, outcome prediction and response to treatments such as immunotherapy. Importantly, the detection of the mutated TERT promoter and TERT mRNA as urinary biomarkers holds great promise for urine-based UC liquid biopsy. In the present article, we review recent mechanistic insights into altered TERT promoter-mediated telomerase activation in UCs and discuss potential clinical implications. Specifically, we compare differences in senescence and transformation between NHUCs and other types of epithelial cells, address the interaction between TERT promoter mutations and other factors to affect UC progression and outcomes, evaluate the impact of TERT promoter mutations and TERT-mediated activation of human endogenous retrovirus genes on UC immunotherapy including Bacillus Calmette-Guérin therapy and immune checkpoint inhibitors. Finally, we suggest the standardization of a TERT assay and evaluation system for UC clinical practice.

IntroductionIn the context of the wide application of digital finance, whether digital finance promotes or inhibits migrant workers' urban integration is an important issue.MethodsBased on microdata from the Chinese Social Survey (CSS) in 2019, we examined the mediation effects of inclusive digital finance on migrant workers' urban integration.ResultsThe empirical results showed that digital finance promotes migrant workers' integration into urban life and has positive effects. When the digital finance index increases by 1 unit, the urban integration of migrant workers also increases by 0.599 units. The usage depth and digitization degree of digital finance are positively correlated with the assimilation process of urban migrant workers, with coefficients of 0.690 and 1.282, respectively. Using the intermediary effect model, it was found that the development of digital finance promotes migrant workers' integration into urban society by narrowing the gender gap in income. One unit of digital finance increases the income of female migrant workers by 144.4% points greater than that of male migrant workers. It significantly improves the ability of female migrant workers to obtain wealth and promotes their integration into cities and family migration.DiscussionIt is necessary to strengthen the promotion and utilization of digital finance to enhance its positive impact on the assimilation process of urban migrant workers by strengthening the construction of digital financial infrastructure, improving supporting policies related to the development of digital finance and improving the financial literacy of migrant workers, especially female migrant workers.

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g., TGFBR2 and EGF). The PPI network contained 212 genes, and HIST1H2BJ, HIST1H2AC, EGF, and EP300 were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (miR-122A, miR-516-5P, miR-507, miR-342, and miR-520F) were predicted to target 112 DEGs. miR-122A reportedly targets both LRP10 and IQGAP1 in the TF-miRNA target regulatory network. The abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

Abstract Background Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co‐factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes. Methods The genomic alterations of the TERT loci including TERT promoter's gain‐of‐function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow‐up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC‐featured telomere/telomerase biology and discuss underlying implications in TC precision medicine. Conclusion Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression‐based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT‐based system and 2022 WHO TC classification may be combined to improve TC care.

Cigar is made of a typical fermented tobacco where the microbiota inhabits within an alkaline environment. Our current understanding on cigar fermentation is far from thorough. This work employed both high-throughput sequencing and chromatography-mass spectrometric technologies to provide new scientific reference for this specific fermented system. Typical cigar samples from different regions (the Caribbeans, South America, East Asia, and Southeast Asia) were investigated. The results show that Firmicutes, Actinobacteria, Proteobacteria, Ascomycota, and Basidiomycota were the predominant phyla in the cigar samples. Rather than the fungal community, it was the bacterial community structures that played vital roles to differentiate the cigar from different regions: Staphylococcus was the dominant genus in the Americas; Bacillus was the dominant genus in Southeast Asia; while in East Asia, there was no dominant genus. Such differences in community structure then affected the microflora metabolism. The correlation between microbiota and metabolites revealed that Aspergillaceae, Cercospora, and Staphylococcus were significantly correlated with sclareolide; Bacillus were positively associated with isophorone. Alcaligenaceae was significantly and positively correlated with L-nicotine and hexadecanoic acid, methyl ester.GRAPHICAL ABSTRACT

Intelligent buildings are among the most active Internet-of-Things (IoT) verticals, encompassing various IoT-enabled devices and sensing technologies for digital transformation. Analysis of spatial data, a very common type of data collected in intelligent buildings, offers a lot of insights for many purposes such as facilitating space management and enhancing the utilization efficiency of buildings. In this paper, we recognize two major challenges in spatial data analysis for intelligent buildings (SDAIB): (1) the complicated analytical contexts that are related to the building space and internal entities and (2) the uncertainty of spatial data due to the limitations of positioning and other sensing technologies. To address these challenges, we identify and categorize different kinds of analytical contexts and spatial data uncertainties in SDAIB, and propose a unified modeling framework for handling them. Furthermore, we showcase how the proposed framework and the associated modeling techniques are used to enable context-aware and uncertainty-aware SDAIB, in the tasks of hotspot discovery, path planning, semantic trajectory generation, and distance monitoring. Finally, we offer several research directions of SDAIB, in line with the emerging trends of the IoT.

BackgroundPhosphogluconate dehydrogenase (PGD) is involved in the regulation of various tumors. However, its role in hepatocellular carcinoma (HCC) is poorly understood. This study tried to determine the prognostic efficacy of PGD and its value for immunotherapy in HCC.MethodsThe data from the TCGA database was used to explore the predictive power of PGD expression and methylation on the overall survival (OS) of HCC through Cox regression and the Kaplan-Meier analysis. Then, we used the GEO and ICGC database to further verify the predictive power. Finally, the relationship between PGD and immune cells and the relationship between PGD and the efficacy of immunotherapy were explored through bioinformatics analysis in HCC.ResultsPGD is highly expressed in HCC tissues, which is negatively regulated by PGD methylation. Low PGD expression and PGD hypermethylation predict better OS in HCC patients. Besides, a meta-analysis based on the TCGA, GSE14520, and ICGC databases further confirms that low PGD expression is closely related to favorable OS. Then, we find significant differences of immune cell infiltrations between high and low PGD expression groups. Expressions of immune checkpoints, most HLA members and tumor mutation burden (TMB) are higher in the high PGD expression group, which indicates beneficial efficacy of immunotherapy in this group. And the potential mechanisms of PGD are exhibited.ConclusionPGD is an independent prognostic factor of HCC patients and plays an important role in immune cell infiltration and immunotherapy, which indicates that PGD can be used as a predictive biomarker for HCC immunotherapy.

BackgroundMyeloid-derived suppressor cells (MDSCs) expansion is an important mechanism underlying immunosuppression during sepsis. Though continuous renal replacement therapy (CRRT) may attenuate hyperinflammatory response in sepsis, its role in regulating MDSCs is unknown. The aim of this study was to assess the potential role of CRRT involved in sepsis-induced MDSCs expansion in pediatric sepsis.MethodThe proportion of polymorphonuclear MDSCs (PMN-MDSCs) was detected before CRRT (pre-CRRT), at 24 hours after CRRT (CRRT 1st day) and on the 7th day after CRRT (CRRT 7th day). The correlation analyses were performed to elucidate the relationship of MDSCs with clinical indexes in sepsis.ResultsTotally 22 pediatric patients with sepsis were enrolled [median age 44 (IQR15, 83) months]. PMN-MDSCs were expanded in pediatric sepsis compared with healthy controls (4.30% vs. 0.37%, P=0.04). The proportion of PMN-MDSCs showed a decreased tendency on the CRRT 7th day compared with that on the CRRT 1st day in survivors (2.29% vs.5.32%, P = 0.088). There was no significant difference in the proportion of PMN-MDSCs between survivors and non-survivors before CRRT (4.51% vs. 3.33%, P=0.745). The levels of interleukin 6 (IL-6) was decreased on the CRRT 7th day compared with CRRT 1st day in survivors. In the subgroups of patients with significantly decreased IL-6 levels after CRRT, the proportion of PMN-MDSCs on the CRRT 7th day were also significantly decreased compared with that on the CRRT 1st day (2.21% vs. 6.67%, P = 0.033).ConclusionThe proportion of PMN-MDSCs was down-regulated on the CRRT 7th day in survivors with sepsis. The reduced PMN-MDSCs expansion may relate to decreased IL-6 level.

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography–mass spectrometry–based (UHPLC–MS/MS–based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.

Electroencephalography (EEG) is widely used for monitoring the depth of anesthesia in surgical patients. Distinguishing age-related EEG features under general anesthesia will help to optimize anesthetic depth monitoring during surgery for elderly patients. This retrospective cohort study included 41 patients aged from 18 to 79 years undergoing noncardiac surgery under general anesthesia. We compared the power spectral signatures and phase–amplitude coupling patterns of the young and elderly groups under baseline and surgical anesthetic depth. General anesthesia by sevoflurane significantly increased the spectral power of delta, theta, alpha, and beta bands and strengthened the cross-frequency coupling both in young and elderly patients. However, the variation in EEG power spectral density and the modulation of alpha amplitudes on delta phases was relatively weaker in elderly patients. In conclusion, the EEG under general anesthesia using sevoflurane exhibited similar dynamic features between young and elderly patients, and the weakened alteration of spectral power and cross-frequency coupling patterns could be utilized to precisely quantify the depth of anesthesia in elderly patients.

Metal-Organic Frameworks (MOFs) offer new ideas for the design of antibacterial materials because of their antibacterial properties, high porosity and specific surface area, low toxicity and good biocompatibility compared with other nanomaterials. Herein, a novel antimicrobial nanomaterial, MIL-101(Fe)@ZnO, has been synthesized by hydrothermal synthesis and characterized by FTIR, UV-vis, ICP-OES, XRD, SEM, EDS and BET to show that the zinc ions are doped into the crystal lattice of MIL-101(Fe) to form a Fe-Zn bimetallic structure. MIL-101(Fe)@ZnO was found to be effective against a wide range of antibacterial materials including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter junii and Staphylococcus epidermidis. It has a significant antibacterial effect, weak cytotoxicity, high safety performance and good biocompatibility. Meanwhile, MIL-101(Fe)@ZnO was able to achieve antibacterial effects by causing cells to produce ROS, disrupting the cell membrane structure, and causing protein leakage and lipid preoxidation mechanisms. In conclusion, MIL-101(Fe)@ZnO is an easy-to-prepare antimicrobial nanomaterial with broad-spectrum bactericidal activity and low toxicity.

Single-cell RNA sequencing (scRNA-seq) has become a powerful technique to investigate cellular heterogeneity and complexity in various fields by revealing the gene expression status of individual cells. Despite the undeniable benefits of scRNA-seq, it is not immune to its inherent limitations, such as sparsity and noise, which would hinder downstream analysis. In this paper, we introduce scCGImpute, a model-based approach for addressing the challenges of sparsity in scRNA-seq data through imputation. After identifying possible dropouts using mixed models, scCGImpute takes advantage of the cellular similarity in the same subpopulation to impute and then uses random forest regression to obtain the final imputation. scCGImpute only imputes the likely dropouts without changing the non-dropout data and can use information from the similarity of cells and genetic correlation simultaneously. Experiments on simulation data and real data were made, respectively, to evaluate the performance of scCGImpute in terms of gene expression recovery and clustering analysis. The results demonstrated that scCGImpute can effectively restore gene expression and improve the identification of cell types.

Industrial added value is an important indicator to measure the operation of the real economy.In order to fully mine the value of power data in the current macroeconomic nowcasting, so as to serve the government policy making, the Bagging and Boosting algorithms in machine learning were applied to nowcast industrial added value based on electric power data as well as traditional statistical data.Firstly, traditional statistical data can significantly improve the forecasting effect of the ARIMA model.Secondly, the nowcasting ability of electric power data depends on the selection of electric power indicators, and the proper electric power index is helpful to predict industrial added value more timely and accurately.Thirdly, the prediction ability of electric power data to the industrial added value in the current period may be lower than that in the future, which means the power data is more likely to be used to predict ahead of time.

In response to the challenges of rural chronic poverty caused by insufficient self-development ability, establishing a development model conducive to poverty alleviation and stimulating rural development potential have become core tasks of deepening rural revitalization. Resources and environment play an important role in invigorating rural vitality. Based on symbiosis theory, we have constructed a new conceptual framework to analyze dynamic performance of rural areas in population, industry and facilities, and dynamic constraints in resources and environment. Using an improved TOPSIS evaluation method and panel Tobit model, we have selected 106 rural revitalization model towns from Shandong province as research samples, empirically analyzed the performance of rural vitality and its resources and environment constraints, explored differences of rural vitality performance and vitality constraints of different village types, and put forward long-term mechanisms to maintain rural vitality. Results show that from 2012 to 2019, rural vitality of rural revitalization model towns in Shandong province was gradually improved, among which industrial development had contributed the most; agriculture-tourism towns are more dynamic than industrialized agriculture towns and characteristic agricultural towns. Through analysis of resources and environment constraints on rural vitality, we found that resources had the greatest impact on rural vitality, and the short-term constraints of total amount restriction on rural vitality were not obvious; binding force of ecological environment on rural vitality changed from weak to strong and increasingly became the bottleneck restricting rural vitality. We have further proposed a long-term mechanism to stimulate rural vitality from the aspects of promoting comprehensive utilization of rural residential land, strengthening concept of ecological priority and green development, taking the road of urban–rural integration, and promoting integrated development of rural industries.

In coal mine goafs, spontaneous combustion of coal can result in methane accumulation, which raises the danger of methane explosion disasters. As an atmospheric control tool, ventilation is applied to ensure air quality for avoiding disasters in underground mines. However, during the process of the spontaneous combustion of coal in coal mine goafs, the impact of ventilation dilution on the possible methane explosions induced by coal combustion has not been well investigated. In this study, a validated gas flow model for the spontaneous coal combustion environment in goafs of coal mines is adopted to investigate the influence of ventilation dilution at the three stages of the spontaneous combustion of coal. The research conclusions suggest that (1) ventilation dilution is a quick measure to dilute methane concentration and intensify heat transfer in the vertical direction in coal mine goafs; (2) ventilation dilution can lessen the danger of methane explosions by diluting methane concentration to the lower explosive limit for methane when coal combustion takes place on the air-inlet side; (3) however, ventilation dilution increases the methane explosion risk by decreasing methane concentration, resulting in explosive methane limits, if coal combustion occurs on the air-return side. This provides a reference for the management of ventilation during a spontaneous coal combustion disaster in the goafs of coal mines with methane.

Hygroscopicity is one of the most important properties of wood and plays a decisive role in its dimensional stability. In this context, conservation plans for waterlogged archaeological wood (WAW) and relevant waterlogged artefacts must be created. The size of the sample required for a moisture sorption assessment may affect the results for (and thus the perception of) the hygroscopicity of a testing artefact. Herein, to investigate the effects of the sample size on the hygroscopicity of WAW as measured via dynamic vapour sorption (DVS), typical WAW and recent (i.e., sound) wood are processed into four differently sized samples, ranging in thickness from 200 mesh to millimetre. The equilibrium moisture contents (EMCs) of the wood samples are simultaneously measured using simultaneous DVS. The sorption isotherms show that the EMC values of the recent wood at each relative humidity increase as the sample size decreases, with the superfine powder sample achieving the highest EMC of all of the recent samples. Although the WAW has a higher EMC than that of recent wood, the effect of the size of the WAW sample on its hygroscopic properties is surprisingly not as pronounced as that for the recent wood. In addition, the hysteresis between the samples of different sizes of the archaeological wood is significantly smaller than that for the reference samples. Furthermore, regarding the standard deviations of the parameters obtained from the Guggenheim Anderson de Boer and Hailwood–Horrobin models, the values for WAW are all much smaller than those for the reference wood. This further verifies the disappearance of the size effect of the hygroscopicity for WAW.

Background: To determine whether neuraxial anesthesia (NA) can improve the success rate of external cephalic version (ECV), and evaluate the clinical outcomes. Methods: This study included 201 consecutive participants who had a breech presentation at term and received ECV between 2014 and 2022. Participants who received ECV without NA were included in Group 1, while participants with NA were included in Group 2. Outcomes assessed were the success rate of ECV and clinical outcomes. Results: In total, 201 participants who had a breech presentation at term and received ECV met the inclusion criteria. Totally, 134 participants performed ECV without NA were included in Group 1, while 67 participants performed the ECV with NA were included in Group 2. The success rate of ECV among the participants was 66.2% (133/201). The rate of placental abruption during or after ECV and neonatal intensive care unit (NICU) admission in Group 2 was statistically significant higher than in the Group 1 (p < 0.05). Conclusions: This study suggested that the use of NA did not increase ECV success rates after 37 weeks of gestation. The recommendation of NA for the ECV may be not suitable for all pregnancies unless the participants request. A large and high-quality study should be conducted to verify the role of NA in ECV, if any.

Previous studies have demonstrated a close relationship between early Parkinson’s disease and functional network abnormalities. However, the pattern of brain changes in the early stages of Parkinson’s disease has not been confirmed, which has important implications for the study of clinical indicators of Parkinson’s disease. Therefore, we investigated the functional connectivity before and after treatment in patients with early Parkinson’s disease, and further investigated the relationship between some topological properties and clinicopathological indicators. We included resting state-fMRI (rs-fMRI) data from 27 patients with early Parkinson’s disease aged 50–75 years from the Parkinson’s Disease Progression Markers Initiative (PPMI). The results showed that the functional connectivity of 6 networks, cerebellum network (CBN), cingulo_opercular network (CON), default network (DMN), fronto-parietal network (FPN), occipital network (OCC), and sensorimotor network (SMN), was significantly changed. Compared to before treatment, the main functional connections were concentrated in the CBN after treatment. In addition, the coefficients of these nodes have also changed. For betweenness centrality (BC), the FPN showed a significant improvement in treatment (p < 0.001). In conclusion, the alteration of functional networks in early Parkinson’s patients is critical for clarifying the mechanisms of early diagnosis of the disease.

Subjective cognitive decline (SCD) is considered to be the preclinical stage of Alzheimer's disease (AD) and has the potential for the early diagnosis and intervention of AD. It was implicated that CSF-tau, which increases very early in the disease process in AD, has a high sensitivity and specificity to differentiate AD from normal aging, and the highly connected brain regions behaved more tau burden in patients with AD. Thus, a highly connected state measured by dynamic functional connectivity may serve as the early changes of AD. In this study, forty-five normal controls (NC), thirty-six individuals with SCD, and thirty-five patients with AD were enrolled to obtain the resting-state functional magnetic resonance imaging scanning. Sliding windows, Pearson correlation, and clustering analysis were combined to investigate the different levels of information transformation states. Three states, namely, the low state, the middle state, and the high state, were characterized based on the strength of functional connectivity between each pair of brain regions. For the global dynamic functional connectivity analysis, statistically significant differences were found among groups in the three states, and the functional connectivity in the middle state was positively correlated with cognitive scales. Furthermore, the whole brain was parcellated into four networks, namely, default mode network (DMN), cognitive control network (CCN), sensorimotor network (SMN), and occipital-cerebellum network (OCN). For the local network analysis, statistically significant differences in CCN for low state and SMN for middle state and high state were found in normal controls and patients with AD. Meanwhile, the differences were also found in normal controls and individuals with SCD. In addition, the functional connectivity in SMN for high state was positively correlated with cognitive scales. Converging results showed the changes in dynamic functional states in individuals with SCD and patients with AD. In addition, the changes were mainly in the high strength of the functional connectivity state.

AimN6-methyladenosine (m6A) modification has been demonstrated to play an important part in hepatitis B virus (HBV) infection and immune response. This study aims to further investigate whether m6A modification plays an important role in the progression of HBV-related liver fibrosis through the regulation of immune cell infiltration.MethodsIn this study, 124 chronically HBV infected cases were obtained from the Gene Expression Omnibus database. In total, 489 m6A-and-stage related genes were selected to be associated with the m6A modification and the stage of liver fibrosis. Based on these genes, we identified two distinct gene clusters, gene clusterA and gene clusterB. The immune characteristics of the two clusters were comprehensively compared. The m6A-S score was constructed as quantification of individual m6A status. The correlations between m6A regulators and infiltrating immune cells were examined and compared in different pairs of groups with various m6A traits.ResultsBiological functions, immune cell infiltration, and cytokines expression were compared between the two gene clusters proving that the gene clusterB was more immune active and had a more advanced liver fibrosis stage. The m6A-S score was associated with immune infiltration and the progression of liver fibrosis. Five different grouping conditions with different m6A traits were set up. According to the intersection of significant genes and cells, ALKBH5 interacting with macrophage and WTAP interacting with nature killer T cells may be key points in the progress of liver fibrosis.ConclusionsN6-methyladenosine modification is closely related to the immune cell infiltration and the fibrosis stage of chronic HBV-infected liver tissue. It provides us a better understanding of the progression of liver cirrhosis via evaluating the m6A modification pattern and immune infiltration characteristics.

Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.

Abstract Background Given poor prognosis and the lack of efficient therapy for advanced hepatocellular carcinoma, immunotherapy has emerged as an increasingly important role. However, there were few reports on the correlation between immune‐related genes and HCC. The purpose of this study is to construct a novel immune‐related gene‐based prognostic signature for HCC and to explore the potential mechanisms. Methods We organized expression data of 374 HCC samples and 50 nontumor samples from TCGA database. A robust signature was constructed by Cox regression analysis based on the immune‐related genes, which were filtered by differential genes analysis and Cox regression analysis. Then, the correlation analysis between the signature and clinical characteristics was conducted. And the signature was validated in ICGC database. Furthermore, the relationships between immune cell infiltration and the signature were explored by bioinformatics analysis. Results Seven genes‐based model (Risk score = BIRC5 * 0.0238 + FOS * 0.0055 + DKK1 * 0.0085 + FGF13 * 0.3432 + IL11 * 0.0135 + IL17D * 0.0878 + SPP1 * 0.0003) was constructed eventually and it was proved to be an independent prognostic factor for HCC patients. The signature‐calculated risk scores were shown to be positively correlated with the infiltration of these five immune cells, including macrophages, neutrophils, CD8+T, dendritic, and B cells. And the results suggested that high amplication of BIRC5, FGF13, IL11, IL17D, and SPP1 were more likely correlated with immune cell infiltration. Finally, PPI network, TFs‐based regulatory network and gene enrichment plots were performed to show potential molecular mechanisms. Conclusion We construct a robust immune‐related gene‐based prognostic signature with seven genes and explore potential mechanisms about it, which may contribute to the immunotherapy research for HCC.

The incidences of nosocomial infections (NIs) are increasing throughout the world, especially for those airborne diseases caused by pathogens or air particulates that float in air. In this study, we designed and manufactured a desk for clinic consultation room air purification and air isolation between doctor and patient. The air isolation and purification (AIP) desk has a high efficiency particulate air (HEPA) filter on the tope and several primary efficiency filters on the sides for air purification. The air circulating between inlet and outlet forms a wind-curtain between doctor and patient. The Computational Fluid Dynamics (CFD) model was used to calculate the speed of the air flow and the angle of sampler. We tested the air purification function of the AIP desk in rooms sized about 3.6 × 2.8 × 2.8 m (L × W × H) and found that the AIP desk could significantly remove the tested air pollutants like smoke particulates and microorganisms like Staphylococcus albus (S. albus)and human adenovirus type 5 (HAdV-5). The wind-curtain can significantly block the exhale air of patient being transmitted to the respiratory area of doctor setting in the opposite of AIP desk. Thus, the AIP desk can be used in hospital setting to reduce the risk of NIs and protect both doctors and patients.

Abstract Background Advances in DNA sequencing have offered researchers an unprecedented opportunity to better study the variety of species living in and on the human body. However, the analysis of microbiome data is complicated by several challenges. First, the sequencing depth may vary by orders of magnitude across samples. Second, species are rare and the data often contain many zeros. Third, the specimen is a fraction of the microbial ecosystem, and so the data are compositional carrying only relative information. Other characteristics of microbiome data include pronounced over-dispersion in taxon abundances, and the existence of a phylogenetic tree that relates all bacterial species. To address some of these challenges, microbiome analysis workflows often normalize the read counts prior to downstream analysis. However, there are limitations in the current literature on the normalization of microbiome data. Results Under the multinomial distribution for the read counts and a prior for the unknown proportions, we propose an empirical Bayes approach to microbiome data normalization. Using a tree-based extension of the Dirichlet prior, we further extend our method by incorporating the phylogenetic tree into the normalization process. We study the impact of normalization on differential abundance analysis. In the presence of tree structure, we propose a phylogeny-aware detection procedure. Conclusions Extensive simulations and gut microbiome data applications are conducted to demonstrate the superior performance of our empirical Bayes method over other normalization methods, and over commonly-used methods for differential abundance testing. Original R scripts are available at GitHub ( https://github.com/liudoubletian/eBay ).

Combined cooling, heating and power (CCHP) microgrid can not only provide a good platform for the development and utilization of clean energy, but also greatly improve the efficiency of energy use, and can improve the quality of power supply and reduce the network loss of the system. In order to make the economic calculation of CCHP microgrid more in line with the actual operation conditions, this paper considered adding battery life to the economic calculation model. The multi-objective optimization model of CCHP microgrid was established considering the power generation cost and the cleanness of microgrid. The multi-objective optimization model was transformed into a single-objective optimization model by the principle of maximum satisfaction. The improved genetic algorithm was used to optimize the output of each micro-source in a day. The effects of multi-objective optimization and single-objective optimization on the output of micro-sources in the CCHP microgrid were compared and analyzed by numerical examples. The simulation results show that the multi-objective optimization model can simultaneously take into account the economic and cleanness of CCHP microgrid, and it is closer to the actual operating conditions of CCHP microgrid.

Abstract Background The Chinese medicine Huoxue Wentong Formula (HXWTF) was used to treat thoracic obstruction and angina pectoris in clinic, which has not been investigated in myocardial ischemia-induced apoptosis and angiogenic function. Here we aimed to investigate the roles of HXWTF in rats with myocardial ischemia-induced apoptosis and angiogenesis disorders, as well as to reveal the potential mechanisms. Methods Male SD rats were subjected to coronary artery ligation followed by HXWTF (420, 840 and 1680 mg/kg/day, p.o.) or isosorbide mononitrate (6.3 mg/kg/day, p.o.) treatment for 4 weeks. Electrocardiogram (ECG) and Echocardiography (ECHO) were used to measure cardiac function. Hematoxylin and eosin (H&E) staining and CD34/α-SMA immunohistochemical staining were performed to observe the ischemic heart sections pathological changes and angiogenesis. Then, the effects on cardiomyocyte apoptosis of H9c2 and tube formation of HCMECs were observed, as well as the changes in the levels of total calmodulin dependent protein kinase II (t-CaMKII), phosphorylated CaMKII (p-CaMKII), oxidized CaMKII (ox-CaMKII), CD34, and Bcl-2/Bax ratio were detected. Results Rats with coronary artery ligation exhibited abnormal cardiac function, enlarged myocardial space, disorderly arranged myocardial fibers, inflammatory cells infiltrated, and aggravated myocardial cell apoptosis, along with angiogenesis dysfunction. The expressions of CD34, p-CaMKII, and ox-CaMKII were elevated and Bcl-2/Bax ratio was diminished in ischemic hearts and H/SD-treated H9c2 or HCMECs, while HXWTF treatment completely rescued angiogenic dysfunction, inhibited cardiomyocyte apoptosis, and down-regulated cardiac CaMKII oxidation and phosphorylation activities. Conclusion Our study demonstrates that HXWTF improves myocardial infarction possibly through inhibiting CaMKII oxidation and phosphorylation levels, facilitating angiogenic function and alleviating cardiomyocyte apoptosis. Thus, therapeutics targeting CaMKII activities may be a promising strategy for rescuing ischemic cardiomyopathy.

Red ginseng is a traditional Chinese herbal medicine that has long been used to treat diabetes, and its blood sugar-lowering activity has been confirmed. However, the mechanism of action of red ginseng on type 2 diabetes mellitus (T2DM) at the metabolic level is still unclear. The purpose of this study is to investigate the effect of red ginseng extract in the treatment of T2DM rats based on untargeted metabolomics. The rat model of T2DM was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), and serum samples were collected after four weeks of treatment. The ultra-high-performance liquid chromatography coupled with Q Exactive HF-X Mass Spectrometer was used to analyze the level of metabolites in serum to evaluate the differences in metabolic levels between different groups. The results of biochemical analysis showed that red ginseng extract intervention significantly improved the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), serum glucose (GLU), and fasting insulin (FINS) after four weeks. Orthogonal partial least squares discriminant analysis was used to study the overall changes of rat metabolomics. After the intervention of red ginseng extract, 50 biomarkers showed a callback trend. Metabolic pathway enrichment analysis showed that the regulated pathways were D-arginine and D-ornithine metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Generally, the results demonstrated that red ginseng extract had beneficial effects on T2DM, which could be mediated via ameliorating the metabolic disorders.

Purpose18F-DCFPyL prostate-specific membrane antigen (PSMA) PET/CT is commonly applied to locate lesions of prostate cancer (PCa), but its diagnostic function of quantitative parameters is ignored. Our study evaluates the parameters of intraprostatic PSMA uptake in patients newly diagnosed with PCa and explores their predictive value in risk classification, which is similar to D’Amico criteria.Materials and MethodsWe quantified the maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion (TL)-PSMA, prostate/muscle (P/M) ratio of the primary tumor, and PSMA-derived tumor volume (PSMA-TV) from 62 patients with histologically proven PCa. Patients newly diagnosed with PCa were allocated into risk groups (at low, intermediate, and high risk, respectively) in accordance with D’Amico criteria. Afterwards, the five parameters mentioned above among three different risk groups were compared, and their predictive values in the risk classification of PCa were explored.ResultsSignificantly decreased levels of SUVmax, SUVmean, TL-PSMA, and P/M ratio were observed in the risk groups of low or intermediate or both, compared with the high-risk group. However, only the P/M ratio significantly elevated in patients with intermediate risk [mean ± SD (median): 46.58 ± 9.74 (45.27), P = 0.042] or high risk [98.95 ± 38.83 (97.52), P < 0.001], compared with low-risk patients [12.33 ± 5.93 (9.81)]. When P/M ratio was used to distinguish between low-risk and intermediate-risk patients, its c-statistics was 0.660. On the other hand, when distinguishing between intermediate-risk and high-risk groups, the c-statistics of P/M ratio was 0.667. Finally, when P/M ratio was used to distinguish between low-risk and high-risk patients, the c-statistics was 0.969. P/M ratio had a positive correlation with prostate-specific antigen in all enrolled PCa patients.ConclusionThe quantitative parameters of 18F-DCFPyL PET/CT, including SUVmax, SUVmean, and P/M ratio, might assist in distinguishing low-risk or intermediate-risk groups from the high-risk group. Of these parameters, P/M ratio appears to be the better promising parameter for risk classification of prostate cancer than SUVmax.

Patients with bipolar disorder have deficits in self-referenced information. The brain functional connectivity during social cognitive processing in bipolar disorder is unclear. Electroencephalogram (EEG) was recorded in 23 patients with bipolar disorder and 19 healthy comparison subjects. We analyzed the time-frequency distribution of EEG power for each electrode associated with self, other, and font reflection conditions and used the phase lag index to characterize the functional connectivity between electrode pairs for 4 frequency bands. Then, the network properties were assessed by graph theoretic analysis. The results showed that bipolar disorder induced a weaker response power and phase lag index values over the whole brain in both self and other reflection conditions. Moreover, the characteristic path length was increased in patients during self-reflection processing, whereas the global efficiency and the node degree were decreased. In addition, when discriminating patients from normal controls, we found that the classification accuracy was high. These results suggest that patients have impeded integration of attention, memory, and other resources of the whole brain, resulting in a deficit of efficiency and ability in self-referential processing.

Analyzing the primary factors of potential evapotranspiration (PET) dynamic is fundamental to accurately estimating crop yield, evaluating environmental impacts, and understanding water and carbon cycles. Previous studies have focused on regionally average regional PET and its dominant factors. Spatial distributions of PET trends and their main causes have not been fully investigated. The Mann-Kendall test was used to determine the significance of long-term trends in PET and five meteorological factors (net radiation, wind speed, air temperature, vapor pressure deficit, relative humidity) at 56 meteorological stations in the Sichuan-Chongqing region from 1970 to 2020. Furthermore, this present study combining and quantitatively illustrated sensitivities and contributions of the meteorological factors to change in annual and seasonal PET. There was a positive trend in PET for approximately 58%, 68%, 38%, 73% and 73% of all surveyed stations at annual, spring, summer, autumn and winter, respectively. Contribution analysis exhibited that the driving factors for the PET variation varied spatially and seasonally. For stations with an upward PET trend, vapor pressure deficit was a dominant factor at all time scales. For stations with a downward PET trend, annual changes in PET mainly resulted from decreased wind speed, as did changes in spring, autumn and winter; decreasing net radiation was the dominant factor in summer. The positive effect of the vapor pressure deficit offset the negative effects of wind speed and net radiation, leading to the increasing PET in this area as a whole. Sensitivity analysis showed that net radiation and relative humidity were the two most sensitive variables for PET, followed by vapor pressure deficit in this study area. Results from the two mathematical approaches were not perfect match, because the change magnitude of the meteorological factors is also responsible for the effects of meteorological factors on PET variation to some extent. However, conducting sensitivity and contribution analysis in this study can avoid the uncertainties from using a single method and provides detailed and well-understood information for interpreting the influence of global climate change on the water cycle and improving local water management.

The timeline of the early lunar bombardment remains unclear. The bombardment rate as a function of time is commonly modeled by three types of shapes: tail-end, sawtooth, and terminal cataclysm. Differently aged melt records the occurrence time of impact events and thus is crucial for constraining the timeline of the early lunar bombardment. Based on a spatially resolved numerical model, we simulate the evolving distribution of differently aged melt with a long-term impact mixing, where different shapes of impact rate function are considered. We compare the outcome of melt age distribution from different scenarios with the actual data from the lunar meteorites and the returned samples. The results suggest that, if the present data are representative of the melt age distribution on the Moon, the shape of the impact rate function is more likely comparable to the tail-end over the sawtooth and the terminal cataclysm, with the terminal cataclysm being least likely. In addition, using state-of-the-art U–Pb dating techniques, more abundant ancient basin melt is likely to be found in returned samples.

Leaf senescence is the final stage of leaf development and is essential for storage properties and crop productivity. WRKY transcription factors have been revealed to play crucial roles in several biological processes during plant growth and development, especially in leaf senescence. However, the functions of Brassica napus WRKY transcription factors in leaf senescence remain unclear. In the present study, Bna.A07.WRKY70, one paralogue of Brassica napus WRKY70, was cloned from the B. napus cultivar “Zhongshuang11 (ZS11)”. We found that Bna.A07.WRKY70 contains a highly conserved WRKY domain and is most closely related to Arabidopsis thaliana WRKY70. The subcellular localization and transcriptional self-activation assays indicated that Bna.A07.WRKY70 functions as a transcription factor. Meanwhile, RT-qPCR and promoter-GUS analysis showed that Bna.A07.WRKY70 is predominantly expressed in the leaves of B. napus and rosette leaves of A. thaliana. In addition, our results demonstrated that ectopic expression of Bna.A07.WRKY70 in A. thaliana wrky70 mutants could restore the senescence phenotypes to wild-type levels. Consistently, the expression levels of three senescence-related marker genes of wrky70 mutants were restored to wild-type levels by ectopic expression of Bna.A07.WRKY70. These findings improve our understanding of the function of Bna.A07.WRKY70 in B. napus and provide a novel strategy for breeding the new stay-green cultivars in rapeseed through genetic manipulation.

Rapeseed (Brassica napus L.) is an important oil crop and a major source of tocopherols, also known as vitamin E, in human nutrition. Enhancing the quality and composition of fatty acids (FAs) and tocopherols in seeds has long been a target for rapeseed breeding. The gene γ-Tocopherol methyltransferase (γ-TMT) encodes an enzyme catalysing the conversion of γ-tocopherol to α-tocopherol, which has the highest biological activity. However, the genetic basis of γ-TMT in B. napus seeds remains unclear. In the present study, BnaC02.TMT.a, one paralogue of Brassica napus γ-TMT, was isolated from the B. napus cultivar “Zhongshuang11” by nested PCR, and two homozygous transgenic overexpression lines were further characterised. Our results demonstrated that the overexpression of BnaC02.TMT.a mediated an increase in the α- and total tocopherol content in transgenic B. napus seeds. Interestingly, the FA composition was also altered in the transgenic plants; a reduction in the levels of oleic acid and an increase in the levels of linoleic acid and linolenic acid were observed. Consistently, BnaC02.TMT.a promoted the expression of BnFAD2 and BnFAD3, which are involved in the biosynthesis of polyunsaturated fatty acids during seed development. In addition, BnaC02.TMT.a enhanced the tolerance to salt stress by scavenging reactive oxygen species (ROS) during seed germination in B. napus. Our results suggest that BnaC02.TMT.a could affect the tocopherol content and FA composition and play a positive role in regulating the rapeseed response to salt stress by modulating the ROS scavenging system. This study broadens our understanding of the function of the Bnγ-TMT gene and provides a novel strategy for genetic engineering in rapeseed breeding.

Previous research shows that ginsenoside Rb3 (G-Rb3) exhibit significant protective effects on cardiomyocytes and is considered a promising treatment for myocardial infraction (MI). However, how to improve its oral bioavailability and reduce its dosage remains to be studied. Previous studies suggest that Ferruginol (FGL) may have synergistic effects with G-Rb3. However, the underlying mechanisms remain to be explored. In this study, left anterior descending branch (LAD) coronary artery ligation or oxygen-glucose deprivation-reperfusion (OGD/R) were used to establish MI models in vivo and in vitro. Subsequently, the pharmacological effects and mechanisms of G-Rb3-FGL were explored by in vitro studies. The results showed that the G-Rb3-FGL co-treatment improved heart functions better than the G-Rb3 treatment alone in MI mice models. Meanwhile, the G-Rb3-FGL co-treatment can upregulate fatty acids oxidation (FAO) and suppress oxidative stress in the heart tissues of MI mice. In vitro studies demonstrated that the synergistic effect of G-Rb3-FGL on FAO, oxidation and inflammation was abolished by RXRα inhibitor HX531 in the H9C2 cell model. In summary, we revealed that G-Rb3 and FGL have a synergistic effect against MI. They protected cardiomyocytes by promoting FAO, inhibiting oxidative stress, and suppressing inflammation through the RXRα-Nrf2 signaling pathway.

Plutella xylostella (L.) is one of the most serious pests of cruciferous vegetables. Our previous work demonstrated that the essential oil of Artemisia lavandulaefolia DC. exhibits promising insecticidal activities against P. xylostella. This study further characterizes the key components that are responsible for the insecticidal effect. In total, 47 compounds (96.52% of the total compounds) were identified from the total oil using GC-MS, and the major compounds were eucalyptol (21.57%), D(+)-camphor (17.33%), (-)-4-terpineol (9.96%) and caryophyllene oxide (10.96%). Among them, (-)-4-terpineol showed significantly larvicidal and fumigant activities against P. xylostella. The LD50 of (-)-4-terpineol was 43.15 mg/mL at 12 h and 31.22 mg/mL at 24 h for 3rd instar larvae, and the LC50 for adults was 8.34 mg/mL at 12 h and 7.35 mg/mL at 24 h. In addition, the adults treated with (-)-4-terpineol showed varying degrees of inhibitory activity toward glutathione S-transferase, catalase, acetylcholinesterase and Na+/K+-ATPase at different post-treatment intervals and concentrations. The results indicate that (-)-4-terpineol has promising insecticidal activities against P. xylostella, and it has good inhibitory effects on the four enzymes of P. xylostella adults.

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging new type of coronavirus that is responsible for the COVID-19 pandemic and the unprecedented global health emergency. Whole-genome sequencing (WGS) of SARS-CoV-2 plays a critical role in understanding the disease. Performance variation exists across SARS-CoV-2 viral WGS technologies, but there is currently no benchmarking study comparing different WGS sequencing protocols. We compared seven different SARS-CoV-2 WGS library protocols using RNA from patient nasopharyngeal swab samples under two storage conditions with low and high viral inputs. We found large differences in mappability and genome coverage, and variations in sensitivity, reproducibility, and precision of single-nucleotide variant calling across different protocols. For certain amplicon-based protocols, an appropriate primer trimming step is critical for accurate single-nucleotide variant calling. We ranked the performance of protocols based on six different metrics. Our findings offer guidance in choosing appropriate WGS protocols to characterize SARS-CoV-2 and its evolution.

Abstract Background Although thyroid dysfunction caused by Hashimoto’s thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice. Methods Female NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot. Results HT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin β3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found. Conclusions These findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.

Summary: Store-operated calcium release-activated calcium (CRAC) channels mediate a variety of cellular signaling functions. The CRAC channel pore-forming protein, Orai1, is a hexamer arranged with 3-fold symmetry. Despite its importance in moving Ca2+ ions into cells, a detailed mechanistic understanding of Orai1 activation is lacking. Herein, a working model is proposed for the putative open state of Orai from Drosophila melanogaster (dOrai), which involves a “twist-to-open” gating mechanism. The proposed model is supported by energetic, structural, and experimental evidence. Fluorescent imaging demonstrates that each subunit on the intracellular side of the pore is inherently strongly cross-linked, which is important for coupling to STIM1, the pore activator, and graded activation of the Orai1 channel. The proposed model thus paves the way for understanding key aspects of calcium signaling at a molecular level. : Biological Sciences; Molecular Biology; Structural Biology Subject Areas: Biological Sciences, Molecular Biology, Structural Biology

Shellac resin ammonium salts (SRAS) were prepared from the natural product of shellac resin and ammonium hydroxide by amidation. Resveratrol (RES) was embedded with SRAS to improve its thermostability, antioxidant activity, and bioavailability. The absorption of RES was promoted in the intestinal tract. Meanwhile, an enteric-coated microcapsule-loaded RES was successfully established by spray drying technology. The RES microcapsule exhibited a spherical shape and perfect stability as well as outstanding sustainable release character in simulated intestinal release experiment. Moreover, SRAS/RES presented a dose-dependent manner with a much higher radical scavenging activity of DPPH· and ABTS+ compared to the pure RES. Therefore, a kind of new pH-sensitive RES microcapsule established may act as a favorable carrier for an insoluble antioxidant ingredient in the potentially new food delivery system on functional food supplements.

SELF-PRUNING 6A (SP6A), a homolog of FLOWERING LOCUS T (FT), has been identified as tuberigen in potato. StSP6A is a mobile signal synthesized in leaves and transmitted to the stolon through phloem, and plays multiple roles in the growth and development of potato. However, the global StSP6A protein interaction network in potato remains poorly understood. In this study, BK-StSP6A was firstly used as the bait to investigate the StSP6A interaction network by screening the yeast two-hybrid (Y2H) library of potato, resulting in the selection of 200 independent positive clones and identification of 77 interacting proteins. Then, the interaction between StSP6A and its interactors was further confirmed by the Y2H and BiFC assays, and three interactors were selected for further expression analysis. Finally, the expression pattern of Flowering Promoting Factor 1.1 (StFPF1.1), No Flowering in Short Days 1 and 2 (StNFL1 and StNFL2) was studied. The three genes were highly expressed in flowers or flower buds. StFPF1.1 exhibited an expression pattern similar to that of StSP6A at the stolon swelling stages. StPHYF-silenced plants showed up-regulated expression of StFPF1.1 and StSP6A, while expression of StNFL1 and StNFL2 was down-regulated in the stolon. The identification of these interacting proteins lays a solid foundation for further functional studies of StSP6A.

The chloroplast, the energy organelle unique to plants and green algae, performs many functions, including photosynthesis and biosynthesis of metabolites. However, as the most critical tuber crop worldwide, the chloroplast proteome of potato (Solanum tuberosum) has not been explored. Here, we use Percoll density gradient centrifugation to isolate intact chloroplasts from leaves of potato cultivar E3 and establish a reference proteome map of potato chloroplast by bottom-up proteomics. A total of 1834 non-redundant proteins were identified in the chloroplast proteome, including 51 proteins encoded by the chloroplast genome. Extensive sequence-based localization prediction revealed over 62% of proteins to be chloroplast resident by at least one algorithm. Sixteen proteins were selected to evaluate the prediction result by transient fluorescence assay, which confirmed that 14 were distributed in distinct internal compartments of the chloroplast. In addition, we identified 136 phosphorylation sites in 61 proteins encoded by chloroplast proteome. Furthermore, we reconstruct the snapshots along starch metabolic pathways in the two different types of plastids by a comparative analysis between chloroplast and previously reported amyloplast proteomes. Altogether, our results establish a comprehensive proteome map with post-translationally modified sites of potato chloroplast, which would provide the theoretical principle for the research of the photosynthesis pathway and starch metabolism.

With the increasing demand for the biodegradable polymer material polylactic acid and its advantage of being metabolized by the human body, L-lactic acid (L-LA) is becoming increasingly attractive in environmental protection and food industry applications. However, the supply of L-LA is not satisfied, and the price is still high. Compared to enzymatic and chemical synthesis methods, L-LA production by microbial fermentation has the advantages of low cost, large yield, simple operation, and environmental protection. This review summarizes the advances in engineering microbial cell factories to produce L-LA. First, the synthetic pathways and microorganisms for L-LA production are outlined. Then, the metabolic engineering strategies for constructing cell factories to overproduce L-LA are summarized and fermentation modes for L-LA production are also given. Finally, the challenges and prospects of the microbial production of L-LA are discussed. This review provides theoretical guidance for researchers engaged in L-LA production.

Abstract The re-emerging human adenovirus types HAdV7, HAdV14, and HAdV55 of species B have caused severe lower respiratory tract diseases and even deaths during recent outbreaks. However, no adenovirus vaccine or therapeutic has been approved for general use. These adenoviruses attach to host cells via the knob domain of the fiber, using human desmoglein 2 as the primary cellular receptor. In this study, a recombinant HAdV11 fiber knob trimer (HAdV11FK) expressed in E. coli was shown to induce broadly neutralizing antibodies against HAdV11, -7, -14p1, and -55 in mice. Using HAdV11FK as an antigen, three monoclonal antibodies, 6A7, 3F11, and 3D8, with high neutralizing activity were generated. More importantly, the results of in vitro neutralization assays demonstrated that 3F11 and 3D8 cross-neutralized HAdV11, -7, and -55, but not HAdV14p1. The amino acids 251KE252 within the F-G loop may be the crucial amino acids in the conformational epitope recognized by 3F11, which is common to HAdV11, -7, -14p, and -55, but is not present in HAdV14p1 and HAdV3. A two-amino-acid deletion in the HAdV14p1 structure breaks the short alpha helix (248SREKE252) that is present in the HAdV7, -11, -55, and -14p fiber knob structures. Our findings add to the knowledge of adenovirus fiber structure and antibody responses and are important for the design of adenovirus vaccines and antiviral drugs with broad activity.

ObjectiveThe aim of this study was to investigate the role of KIF26A in breast cancer.MethodqRT-PCR and immunohistochemistry were conducted to explore KIF26A expression and functional contribution to breast cancer development. MTS, EDU, colony formation assays, and flow cytometry analysis were conducted to assess cell proliferation characteristics and cell cycle progression. A series of 5′-flanking region deletion plasmids and mutating the binding site, with the luciferase reporter assay, were used to identify the core promotor region of KIF26A. The prediction by software and construction of the transcriptional factor plasmids were used to identify the transcriptional factor. Chromatin immunoprecipitation assay could demonstrate transcriptional factor directly binding to the KIF26A promoter. Human Genome Oligo Microarray Assay and gene ontology (GO) and pathway analyses were used to predict the downstream pathway.ResultsOur results showed that in breast cancer tissues, elevated KIF26A expression was significantly correlated with lymph node metastasis. KIF26A could promote proliferation and G0/G1 phase cell cycle progression in breast cancer cells. The core promoter region of the human KIF26A gene was located upstream of the transcription start site at position −395 to −385. The transcriptional factor E2F1 was shown to activate KIF26A expression. Furthermore, KIF26A was shown to inhibit the expression of p21, then activate CDK–RB–E2Fs pathway. The elevated E2F1 can activate the cell cycle progression and the KIF26A expression, forming feedback loop.ConclusionsThe present study demonstrated that KIF26A, directly upregulated by E2F1, promoted cell proliferation and cell cycle progression via CDK–RB–E2Fs feedback loop in breast cancer.

A strongly coupled monolithic method was previously proposed for the computation of wind-induced fluid-structure interaction of flexible membranous structures by the authors. How to obtain the accurate solution is a key issue for the strongly coupled monolithic method. Projection methods are among the commonly used methods for the coupled solution. In the work here, to impose initial pressure boundary conditions implicitly defined in the original momentum equations in classical projection methods when dealing with large-displacement of membranous structures, a modified factor is introduced in corrector step of classical projection methods and a new modified projection method is obtained. The solution procedures of the modified projection method aimed at strongly coupled monolithic equations are given, and the related equations are derived. The proposed method is applied to the computation of a two-dimensional fluid-structure interaction benchmark case and wind-induced fluid-structure interaction of a three-dimensional flexible membranous structure. The performance and efficiency of the modified projection method are evaluated. The results show that the modified projection methods are valid in the computation of wind-induced fluid-structure interaction of flexible membranous structures, with higher accuracy and efficiency compared with traditional methods. The modified value has little effects on the computation results whereas iteration times has significant effects. Computation accuracy can be improved greatly by increasing iteration times with less increase in computation time and little effects on stability with the modified projection method.