Genome-wide association study reveals the genes associated with the leaf inclusion contents in Chinese medical tree Eucommia ulmoides.

Eucommia ulmoides is an economic tree that can biosynthesize secondary metabolites with pharmacological functions. Genetic basis of biosynthesis of these compounds is almost unknown. Therefore, genomic-wide association study was performed to exploit the genetic loci maybe involved in biosynthetic pathways of 5 leaf inclusions (aucubin, chlorogenic acid, gutta-percha, polyphenols, total flavonoids). It was shown that contents of the 5 leaf metabolites have a wide variation following normal distribution. A total of 2 013 102 single nucleotide polymorphism (SNP) markers were identified in a population containing 62 individual clones. Through genome-wide association study analysis, many SNP loci were identified perhaps associated with phenotypes of the leaf inclusions. Higher transcriptional levels of the candidate genes denoted by significant SNPs in leaves suggested they may be involved in biosynthesis of the leaf inclusions. These genetic loci provide with invaluable information for further studies on the gene functions in biosynthesis of the leaf inclusions and selective breeding of the plus trees.

A novel DNA methylation motif identified in Bacillus pumilus BA06 and possible roles in the regulation of gene expression.

Single-molecule real-time (SMRT) sequencing can be used to identify a wide variety of chemical modifications of the genome, such as methylation. Here, we applied this approach to identify N6-methyl-adenine (m6A) and N4-methyl-cytosine (m4C) modification in the genome of Bacillus pumilus BA06. A typical methylation recognition motif of the type I restriction-modification system (R-M), 5'-TCm6AN8TTGG-3'/3'-AGTN8m6AACC-5', was identified. We confirmed that this motif was a new type I methylation site using REBASE analysis and that it was recognized by a type I R-M system, Bpu6ORFCP, according to methylation sensitivity assays in vivo and vitro. Furthermore, we found that deletion of the R-M system Bpu6ORFCP induced transcriptional changes in many genes and led to increased gene expression in pathways related to ABC transporters, sulfur metabolism, ribosomes, cysteine and methionine metabolism and starch and sucrose metabolism, suggesting that the R-M system in B. pumilus BA06 has other significant biological functions beyond protecting the B. pumilus BA06 genome from foreign DNA.

Characterization of a Protease Hyper-Productive Mutant of Bacillus pumilus by Comparative Genomic and Transcriptomic Analysis.

Bacillus pumilus BA06 has great potential for the production of alkaline proteases. To improve the protease yield, classical mutagenesis to combine the physical and chemical mutagens was performed to obtain a protease hyper-productive mutant SCU11. The full genome sequences of BA06 and SCU11 strains were assembled through DNA sequencing using the PacBio sequencing platform. By comparative genomics analysis, 147 SNPs and 15 InDels were found between these two genomes, which lead to alternation of coding sequence in 15 genes. Noticeable, the gene (kinA) encoding sporulation kinase A is interrupted by introducing a stop codon in its coding region in BA06. Interestedly, this gene is reversely corrected in SCU11. Furthermore, comparative transcriptome analysis revealed that kinA and two positive regulatory genes (DegU and Spo0A) were upregulated in transcription in SCU11. In terms of the transcriptional data, upregulation of a phosphorylation cascade starting with KinA may enhance Spo0A phosphorylation, and thus activate expression of the gene aprE (encoding major extracellular protease) through repression of AbrB (a repressor of aprE) and activation of SinI, an antagonist of SinR (a repressor of aprE). In addition, the other genes involved in various metabolic pathways, especially of membrane transport and sporulation, were altered in transcription between these two strains. Conclusively, our transcriptome data suggested that upregulation degU and spo0A, as well as kinA, may at least partially contribute to the high production of alkaline protease in SCU11.

Disruption of the pleiotropic gene scoC causes transcriptomic and phenotypical changes in Bacillus pumilus BA06.

BACKGROUND: Bacillus pumilus is a Gram-positive and endospore-forming bacterium broadly existing in a variety of environmental niches. Because it produces and secrets many industrially useful enzymes, a lot of studies have been done to understand the underlying mechanisms. Among them, scoC was originally identified as a pleiotropic transcription factor negatively regulating protease production and sporulation in B. subtilis. Nevertheless, its role in B. pumilus largely remains unknown. RESULTS: In this study we successfully disrupted scoC gene in B. pumilus BA06 and found increased total extracellular protease activity in scoC mutant strain. Surprisingly, we also found that scoC disruption reduced cell motility possibly by affecting flagella formation. To better understand the underlying mechanism, we performed transcriptome analysis with RNA sequencing. The result showed that more than one thousand genes were alternated at transcriptional level across multiple growth phases, and among them the largest number of differentially expressed genes (DEGs) were identified at the transition time point (12 h) between the exponential growth and the stationary growth phases. In accordance with the altered phenotype, many protease genes especially the aprE gene encoding alkaline protease were transcriptionally regulated. In contrast to the finding in B. subtilis, the aprN gene encoding neutral protease was transcriptionally downregulated in B. pumilus, implicating that scoC plays strain-specific roles. CONCLUSIONS: The pleiotropic transcription factor ScoC plays multiple roles in various cellular processes in B. pumilus, some of which were previously reported in B. subtilis. The supervising finding is the identification of ScoC as a positive regulator for flagella formation and bacterial motility. Our transcriptome data may provide hints to understand the underlying mechanism.

Transcriptome profiling analysis reveals metabolic changes across various growth phases in Bacillus pumilus BA06.

BACKGROUND: Bacillus pumilus can secret abundant extracellular enzymes, and may be used as a potential host for the industrial production of enzymes. It is necessary to understand the metabolic processes during cellular growth. Here, an RNA-seq based transcriptome analysis was applied to examine B. pumilus BA06 across various growth stages to reveal metabolic changes under two conditions. RESULTS: Based on the gene expression levels, changes to metabolism pathways that were specific to various growth phases were enriched by KEGG analysis. Upon entry into the transition from the exponential growth phase, striking changes were revealed that included down-regulation of the tricarboxylic acid cycle, oxidative phosphorylation, flagellar assembly, and chemotaxis signaling. In contrast, the expression of stress-responding genes was induced when entering the transition phase, suggesting that the cell may suffer from stress during this growth stage. As expected, up-regulation of sporulation-related genes was continuous during the stationary growth phase, which was consistent with the observed sporulation. However, the expression pattern of the various extracellular proteases was different, suggesting that the regulatory mechanism may be distinct for various proteases. In addition, two protein secretion pathways were enriched with genes responsive to the observed protein secretion in B. pumilus. However, the expression of some genes that encode sporulation-related proteins and extracellular proteases was delayed by the addition of gelatin to the minimal medium. CONCLUSIONS: The transcriptome data depict global alterations in the genome-wide transcriptome across the various growth phases, which will enable an understanding of the physiology and phenotype of B. pumilus through gene expression.

Identification of weak transitions using moving-window two-dimensional correlation analysis: treatment with scaling techniques.

In the present study, the theory of the data treatment with scaling techniques for moving-window two-dimensional (scaling-MW2D) correlation analysis was first proposed. This new analytical method of spectroscopy can significantly enhance the resolving capacity of the moving-window two-dimensional (MW2D) correlation infrared spectroscopy in the direction of the perturbation variable. So, it strengthened the ability of MW2D to highlight the weak transitions. The in situ infrared spectra of four common polymers, including polyamide 66 (PA66), polystyrene-block-polybutadiene-block-polystyrene block copolymer (SBS), isotactic polypropylene (iPP), and polyoxymethylene (POM), were employed to illustrate the advantages of scaling-MW2D. In the applications of the present study, the conventional autocorrelation MW2D can only distinguish the melting point of PA66, the maximum crystallization temperature of POM, and the primary oxidation of SBS. However, the autocorrelation scaling-MW2D not only can more easily determine the above transitions, but also can identify PA66 brill transition, the dissociation of adsorbed water in PA66, POM secondary crystallization, the glass transition of hard blocks in SBS, and the generation of the aldehyde and hydroxyl groups during SBS oxidation. Our further study found that the selection of the scaling factor α was very important. The golden point α = 0.618 was the best value, and satisfactory application results can be achieved. The slice scaling-MW2D was also investigated. The scaling-MW2D method of spectroscopy can be used elsewhere. The application of this analytical method should not be limited to the infrared spectra, and it also should not be limited to transitions in polymers. This method can be easily extended and applied to other materials and spectra.

Mining User Reviews From Hypertension Management Mobile Health Apps to Explore Factors Influencing User Satisfaction and Their Asymmetry: Comparative Study.

BACKGROUND: Hypertension significantly impacts the well-being and health of individuals globally. Hypertension management apps (HMAs) have been shown to assist patients in controlling blood pressure (BP), with their efficacy validated in clinical trials. However, the utilization of HMAs continues to be suboptimal. Presently, there is a dearth of real-world research based on big data and exploratory mining that compares Chinese and American HMAs. OBJECTIVE: This study aims to systematically gather HMAs and their user reviews from both China and the United States. Subsequently, using data mining techniques, the study aims to compare the user experience, satisfaction levels, influencing factors, and asymmetry between Chinese and American users of HMAs. In addition, the study seeks to assess the disparities in satisfaction and its determinants while delving into the asymmetry of these factors. METHODS: The study sourced HMAs and user reviews from 10 prominent Chinese and American app stores globally. Using the latent Dirichlet allocation (LDA) topic model, the research identified various topics within user reviews. Subsequently, the Tobit model was used to investigate the impact and distinctions of each topic on user satisfaction. The Wald test was applied to analyze differences in effects across various factors. RESULTS: We examined a total of 261 HMAs along with their associated user reviews, amounting to 116,686 reviews in total. In terms of quantity and overall satisfaction levels, Chinese HMAs (n=91) and corresponding reviews (n=16,561) were notably fewer compared with their American counterparts (n=220 HMAs and n=100,125 reviews). The overall satisfaction rate among HMA users was 75.22% (87,773/116,686), with Chinese HMAs demonstrating a higher satisfaction rate (13,866/16,561, 83.73%) compared with that for American HMAs (73,907/100,125, 73.81%). Chinese users primarily focus on reliability (2165/16,561, 13.07%) and measurement accuracy (2091/16,561, 12.63%) when considering HMAs, whereas American users prioritize BP tracking (17,285/100,125, 17.26%) and data synchronization (12,837/100,125, 12.82%). Seven factors (easy to use: P<.001; measurement accuracy: P<.001; compatibility: P<.001; cost: P<.001; heart rate detection function: P=.02; blood pressure tracking function: P<.001; and interface design: P=.01) significantly influenced the positive deviation (PD) of Chinese HMA user satisfaction, while 8 factors (easy to use: P<.001; reliability: P<.001; measurement accuracy: P<.001; compatibility: P<.001; cost: P<.001; interface design: P<.001; real-time: P<.001; and data privacy: P=.001) affected the negative deviation (ND). Notably, BP tracking had the greatest effect on PD (ß=.354, P<.001), while cost had the most significant impact on ND (ß=3.703, P<.001). All 12 factors (easy to use: P<.001; blood pressure tracking function: P<.001; data synchronization: P<.001; blood pressure management effect: P<.001; heart rate detection function: P<.001; data sharing: P<.001; reliability: P<.001; compatibility: P<.001; interface design: P<.001; advertisement distribution: P<.001; measurement accuracy: P<.001; and cost: P<.001) significantly influenced the PD and ND of American HMA user satisfaction. Notably, BP tracking had the greatest effect on PD (ß=0.312, P<.001), while data synchronization had the most significant impact on ND (ß=2.662, P<.001). In addition, the influencing factors of PD and ND in user satisfaction of HMA in China and the United States are different. CONCLUSIONS: User satisfaction factors varied significantly between different countries, showing considerable asymmetry. For Chinese HMA users, ease of use and interface design emerged as motivational factors, while factors such as cost, measurement accuracy, and compatibility primarily contributed to user dissatisfaction. For American HMA users, motivational factors were ease of use, BP tracking, BP management effect, interface design, measurement accuracy, and cost. Moreover, users expect features such as data sharing, synchronization, software reliability, compatibility, heart rate detection, and nonintrusive advertisement distribution. Tailored experience plans should be devised for different user groups in various countries to address these diverse preferences and requirements.

Identification and validation of DHCR7 as a diagnostic biomarker involved in the proliferation and mitochondrial function of breast cancer.

BACKGROUND: Energy metabolism has a complex intersection with pathogenesis and development of breast cancer (BC). This allows for the possibility of identifying energy-metabolism-related genes (EMRGs) as novel prognostic biomarkers for BC. 7-dehydrocholesterol reductase (DHCR7) is a key enzyme of cholesterol biosynthesis involved in many cancers, and in this paper, we investigate the effects of DHCR7 on the proliferation and mitochondrial function of BC. METHODS: EMRGs were identified from the Gene Expression Omnibus (GEO) and MSigDB databases using bioinformatics methods. Key EMRGs of BC were then identified and validated by functional enrichment analysis, interaction analysis, weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Cox analysis, and immune infiltration. Western blot, qRT-PCR, immunohistochemistry (IHC), MTT assay, colony formation assay and flow cytometry assay were then used to analyze DHCR7 expression and its biological effects on BC cells. RESULTS: We identified 31 EMRGs in BC. These 31 EMRGs and related transcription factors (TFs), miRNAs, and drugs were enriched in glycerophospholipid metabolism, glycoprotein metabolic process, breast cancer, and cell cycle. Crucially, DHCR7 was a key EMRG in BC identified and validated by WGCNA, LASSO regression and receiver operating characteristic (ROC) curve analysis. High DHCR7 expression was significantly associated with tumor immune infiltration level, pathological M, and poor prognosis in BC. In addition, DHCR7 knockdown inhibited cell proliferation, induced apoptosis and affected mitochondrial function in BC cells. CONCLUSIONS: DHCR7 was found to be a key EMRG up-regulated in BC cells. This study is the first to our knowledge to report that DHCR7 acts as an oncogene in BC, which might become a novel therapeutic target for BC patients.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

A rat model of metabolic syndrome-related heart failure with preserved ejection fraction phenotype: pathological alterations and possible molecular mechanisms.

Background: Heart failure with preserved ejection fraction (HFpEF) represents a syndrome involving multiple pathophysiologic disorders and clinical phenotypes. This complexity makes it challenging to develop a comprehensive preclinical model, which presents an obstacle to elucidating disease mechanisms and developing new drugs. Metabolic syndrome (MetS) is a major phenotype of HFpEF. Thus, we produced a rat model of the MetS-related HFpEF phenotype and explored the molecular mechanisms underpinning the observed pathological changes. Methods: A rat model of the MetS-related HFpEF phenotype was created by feeding spontaneously hypertensive rats a high-fat-salt-sugar diet and administering streptozotocin solution intraperitoneally. Subsequently, pathological changes in the rat heart and their possible molecular mechanisms were explored. Results: The HFpEF rats demonstrated primary features of MetS, such as hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and cardiac anomalies, such as left ventricular (LV) remodeling and diastolic impairment, and left atrial dilation. Additionally, inflammation, myocardial hypertrophy, and fibrosis were observed in LV myocardial tissue, which may be associated with diverse cellular and molecular signaling cascades. First, the inflammatory response might be related to the overexpression of inflammatory regulators (growth differentiation factor 15 (GDF-15), intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1)). Secondly, phosphorylated glycogen synthase kinase 3ß (GSK-3ß) may stimulate cardiac hypertrophy, which was regulated by activated -RAC-alpha serine/threonine-protein kinase (AKT). Finally, the transforming growth factor-ß1 (TGF-ß1)/Smads pathway might regulate collagen production and fibroblast activation, promoting myocardial fibrosis. Conclusion: The HFpEF rat replicates the pathology and clinical presentation of human HFpEF with MetS and may be a reliable preclinical model that helps elucidate HFpEF pathogenesis and develop effective treatment strategies.

Fabrication of stable solid fluorescent starch materials based on Hantzsch reaction.

In this paper, a series of fluorescent starches were prepared simply and effectively by Hantzsch multi-component reaction (MRC). These materials showed bright fluorescence emission. Notably, due to the existence of polysaccharide skeleton, starch molecules can effectively inhibit the common aggregation induced quenching effect caused by the aggregation of conjugated molecules in traditional organic fluorescent materials. Meanwhile, the stability of this material is so excellent that the fluorescence emission of the dried starch derivatives would not destroy after boiling at a high temperature in some common solvents, and even brighter fluorescence can be stimulated in alkaline solution. In addition to fluorescence, starch was also endowed with hydrophobic property by one-pot method connecting long alkyl chains. Compared with native starch, the contact angle of fluorescent hydrophobic starch increased from 29° to 134°. Furthermore, the fluorescent starch can be prepared into film, gel and coating by different processing methods. The preparation of these Hantzsch fluorescent starch materials provide a new way for the functional modification of starch materials and has great application potential in detecting, anti-counterfeiting, security printing and other related fields.

Ling-Gui-Qi-Hua formula alleviates left ventricular myocardial fibrosis in rats with heart failure with preserved ejection fraction by blocking the transforming growth factor-ß1 /Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown. AIM OF THE STUDY: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway from the perspective of animal experiments. MATERIALS AND METHODS: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-ß1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-ß1/Smads pathways. RESULTS: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-ß1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-ß1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-ß1/Smads pathway. CONCLUSION: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-ß1/Smads pathways in HFpEF rats.

Monoclonal antibodies constructed from COVID-19 convalescent memory B cells exhibit potent binding activity to MERS-CoV spike S2 subunit and other human coronaviruses.

Introduction: The Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two highly contagious coronaviruses causing MERS and COVID-19, respectively, without an effective antiviral drug and a long-lasting vaccine. Approaches for diagnosis, therapeutics, prevention, etc., particularly for SARS-CoV-2 that is continually spreading and evolving, are urgently needed. Our previous study discovered that >60% of sera from convalescent COVID-19 individuals, but <8% from general population, showed binding activity against the MERS-CoV spike protein, indicating that SARS-CoV-2 infection boosted antibodies cross-reactive with MERS-CoV. Methods: To generate antibodies specific to both SARS-CoV-2 and MERS-CoV, here we screened 60 COVID-19 convalescent sera against MERS-CoV spike extracellular domain and S1 and S2 subunits. We constructed and characterized monoclonal antibodies (mAbs) from COVID-19 convalescent memory B cells and examined their binding and neutralizing activities against human coronaviruses. Results and Discussion: Of 60 convalescent serum samples, 34 showed binding activity against MERS-CoV S2, with endpoint titers positively correlated with the titers to SARS-CoV-2 S2. By sorting single memory B cells from COVID-19 convalescents, we constructed 38 mAbs and found that 11 mAbs showed binding activity with MERS-CoV S2, of which 9 mAbs showed potent cross-reactivity with all or a proportion of spike proteins of alphacoronaviruses (229E and NL63) and betacoronaviruses (SARS-CoV-1, SARS-CoV-2, OC43, and HKU1). Moreover, 5 mAbs also showed weak neutralization efficiency against MERS-CoV spike pseudovirus. Epitope analysis revealed that 3 and 8 mAbs bound to linear and conformational epitopes in MERS-CoV S2, respectively. In summary, we have constructed a panel of antibodies with broad-spectrum reactivity against all seven human coronaviruses, thus facilitating the development of diagnosis methods and vaccine design for multiple coronaviruses.

Analysis of the effects of Zhenju antihypertensive tablet on efficacy, safety and vascular endothelial function in patients with essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: : As a compound preparation of traditional Chinese and western medicine included in Volume 20 of Chinese traditional Medicine prescription, Zhenju antihypertensive tablet has been widely used in the treatment of patients with essential hypertension (EH) for many years. This study intends to evaluate the efficacy, safety and vascular endothelial function of Zhenju antihypertensive tablet in the treatment of essential hypertension. METHODS: : The search strategies of different websites were searched on Cochrane Central controlled Trials Registry, PubMed, excerpt database, Chinese Biomedical Literature Database, China National knowledge Infrastructure, Chinese Science and Technology Journal Database, WanFang, and other websites. All qualified studies were confirmed to include randomized controlled trials. The search time range was from January 1, 1900 to August 31, 2021. At the same time, the list of references and related reviews were checked. Two evaluators were responsible for the extraction and management of the data independently. The literature quality was evaluated according to Cochrane manual 4.2.2. Heterogeneity test and Meta analysis were carried out by Review ManagerV.5.3 software. The bias risk included in the study was evaluated by Cochrane "bias risk" tool. In addition, the relevant statistical data were evaluated by GRADE3.6 evidence quality grading system. RESULTS: : This study intends evaluate the efficacy and safety of Zhenju antihypertensive tablet in the treatment of EH from 4 aspects, including changes in blood pressure (systolic blood pressure, diastolic Blood pressure), effective hypotension, changes in endothelial function (NO, the level of plasma endothelin-1 in serum), and adverse reactions. CONCLUSION: : The conclusion of this study intends to provide evidence for judging the effectiveness and safety of ZJAHC intervention on EH patients and their endothelial function.PROSPERO registration number: PROSPERO CRD42021235309.

Efficacy and safety of Xuanfei Baidu granules for treating COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) is currently prevalent in most countries around the world. It has become a common threat to global human health because there is no specific cure and no targeted treatment for this disease at this stage. Xuanfei Baidu granule (XFBD) included the traditional Chinese medicine prescription in COVID-19 diagnosis and treatment Plan (trial eighth Edition) released in August 2020, which has played a great role in the diagnosis and treatment of COVID-19 in Wuhan, China. This paper intends to evaluate the efficacy and safety of Xuanfei Baidu granule in the treatment of COVID-19. METHODS: The search strategies of different websites were searched on Cochrane Central controlled Trials Registry, PubMed, excerpt database, Web of science, China National knowledge Infrastructure, Chinese Science and Technology Journal Database, WanFang and other websites. All qualified studies were confirmed to include randomized controlled trials. The search time range was from January 1, 2019 to February 28, 2021. In the meanwhile, the list of references and related reviews was checked. Two evaluators were responsible for the extraction and management of the data independently. The literature quality was evaluated according to Cochrane manual 4.2.2. Heterogeneity test and Meta analysis were carried out by Review Manager V.5.3 software. The bias risk included in the study was evaluated by Cochrane "bias risk" tool, and the relevant statistical data were evaluated by GRADE3.6 evidence quality grading system. RESULTS: This study intends to evaluate the efficacy and safety of XFBD in the treatment of COVID-19 from 4 aspects, including nucleic acid negative conversion time, average hospital stay, clinical symptom improvement rate and lung computed tomography improvement rate. CONCLUSION: The conclusion of this scheme intends to provide evidence for judging whether the intervention of XFBD on COVID-19 patients is effective or not. PROSPERO REGISTRATION NUMBER: CRD42021245640.

Efficacy and safety of Yangxue Qingnao granules for the treatment of essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Essential hypertension is a major risk factor for many fatal cardiovascular and cerebrovascular diseases and has become a heavy burden on families and society. At present, the prevention and treatment of essential hypertension is still unsatisfactory. Yangxue Qingnao granules is a kind of Chinese patent medicine that has been used to treat essential hypertension. The objective of this protocol is to systematically evaluate the efficacy and safety of Yangxue Qingnao granules in the treatment of essential hypertension. METHODS: Randomized controlled trials on Yangxue Qingnao granules for essential hypertension will be searched from the following databases: PubMed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database, and China Biology Medicine disc from inception to August 27, 2021, regardless of language. Study screening and data extraction will be carried out by two independent reviewers. The quality of the included studies will be assessed using Cochrane risk-of-bias tool for randomized trials. Statistic analysis will be performed using RevMan 5.3 software. The quality of evidence will be assessed using GRADE approach. RESULTS: This study will systematically evaluate the efficacy and safety of Yangxue Qingnao granules in the treatment of essential hypertension and provide high-quality evidence for clinical practice. CONCLUSION: The findings of this systematic review will provide high-quality evidence to verify the efficacy and safety of Yangxue Qingnao granules in the treatment of essential hypertension. INPLASY REGISTRATION NUMBER: INPLASY202190015.

Efficacy and safety of Shugan Jieyu capsule in the treatment of essential hypertension with insomnia, anxiety or depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Shugan Jieyu capsule can reduce blood pressure and improve its concomitant symptoms. However, it is not widely used in clinic because of its incomplete understanding of its nature. There are many reports on the clinical trials of Shugan Jieyu capsule in the treatment of essential hypertension with insomnia, anxiety or depression in recent years. However, the lack of systematic review and meta-analysis has not provided effective evidence. As a consequence, we provide a protocol to evaluate the efficacy and safety of Shugan Jieyu capsule (SJC) in the treatment of essential hypertension (EH) with insomnia, anxiety or depression. METHODS: The search time range of Cochrane Library, PubMed, excerpt Database (EMBASE), Chinese Biomedical Literature Database (CBM), China National knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wanfang Database (WanFang), was searched by computer from the establishment of the database to December 31, 2020. In the meanwhile, the list of references and related reviews were checked. The data were extracted by 2 evaluators independently, and the literature quality was evaluated according to Cochrane manual 4.2.2. In addition, CochraneRevman5.3 software was used for heterogeneity test, meta-analysis, publication bias analysis and GRADE3.6 evidence quality classification system evaluation related statistical data. RESULTS: This study intends to evaluate the efficacy and safety of SJC in the treatment of EH from many aspects, including changes in blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP)], effective rate of blood pressure reduction, improvement rate of concomitant symptoms and adverse reactions. CONCLUSION: The conclusion of systematic review intends to provide evidence for judging that SJC is an effective intervention for EH patients with insomnia, anxiety and depression. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42021219704.

Efficacy and safety of Xinkeshu in the treatment of angina pectoris of coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The incidence of angina pectoris (AP) of coronary heart disease (CHD) is increasing in the world, which seriously affects people's lives and brings a huge economic burden. The clinical research on Xinkeshu (XKS) in the treatment of AP of CHD has been increasing. However, there is no systematic review and meta-analysis. This study intends to provide a basis for systematically evaluating the efficacy and safety of XKS combined with conventional western medicine in the treatment of AP of CHD. METHODS: CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, and EMbase databases were searched for the period from the establishment of the database to August 31, 2021. The clinical randomized controlled trials of XKS in the treatment of AP of CHD were collected. Two systematic reviewers independently selected the literature, extracted the data, and evaluated the quality according to the inclusion and exclusion criteria. The methodological quality of the literature was evaluated using Cochrane Handbook 5.3.0 bias risk assessment tool, RevMan 5.3.0 software was used for meta-analysis and GRADE3.6 evidence quality grading system was used to evaluate the quality. RESULTS: This study intended to evaluate the efficacy and safety of XKS in the treatment of AP of CHD from many aspects, including the frequency of AP, the duration of AP, the dosage of nitroglycerin, and the efficacy of ECG (total effective rate = markedly effective + effective). The secondary indicators included the efficacy of AP (total effective rate = significant + effective), blood lipids (triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), hemorheology (whole blood viscosity, plasma viscosity, and fibrinogen), serum factors (C-reactive protein, endothelin-1, homocysteine, and nitric oxide), and adverse drug reactions. CONCLUSION: The conclusion of the systematic review intended to provide clear evidence of clinical application of XKS combined with conventional western medicine in the treatment of AP of CHD, which can be widely used in the clinic.

FastEmbed: Predicting vulnerability exploitation possibility based on ensemble machine learning algorithm.

In recent years, the number of vulnerabilities discovered and publicly disclosed has shown a sharp upward trend. However, the value of exploitation of vulnerabilities varies for attackers, considering that only a small fraction of vulnerabilities are exploited. Therefore, the realization of quick exclusion of the non-exploitable vulnerabilities and optimal patch prioritization on limited resources has become imperative for organizations. Recent works using machine learning techniques predict exploited vulnerabilities by extracting features from open-source intelligence (OSINT). However, in the face of explosive growth of vulnerability information, there is room for improvement in the application of past methods to multiple threat intelligence. A more general method is needed to deal with various threat intelligence sources. Moreover, in previous methods, traditional text processing methods were used to deal with vulnerability related descriptions, which only grasped the static statistical characteristics but ignored the context and the meaning of the words of the text. To address these challenges, we propose an exploit prediction model, which is based on a combination of fastText and LightGBM algorithm and called fastEmbed. We replicate key portions of the state-of-the-art work of exploit prediction and use them as benchmark models. Our model outperforms the baseline model whether in terms of the generalization ability or the prediction ability without temporal intermixing with an average overall improvement of 6.283% by learning the embedding of vulnerability-related text on extremely imbalanced data sets. Besides, in terms of predicting the exploits in the wild, our model also outperforms the baseline model with an F1 measure of 0.586 on the minority class (33.577% improvement over the work using features from darkweb/deepweb). The results demonstrate that the model can improve the ability to describe the exploitability of vulnerabilities and predict exploits in the wild effectively.

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter® CTC capture system in patients with breast cancer.

PURPOSE: In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). METHODS: A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter® , a microfluidic-based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. RESULTS: Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1-4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut-off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. CONCLUSION: Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.