Search

Objectives: To explore the connection of hypertension and severe COVID-19 outcomes.Methods: A total of 68 observational studies recording mortality and/or general severity of COVID-19 were pooled for meta-analyses of the relationship of severe COVID-19 outcomes with hypertension as well as systolic and diastolic blood pressure. Genome-wide cross-trait meta-analysis (GWCTM) was performed to explore the genes linking between hypertension and COVID-19 severity.Results: The results of meta-analysis with the random effect model indicated that pooled risk ratios of hypertension on mortality and severity of COVID-19 were 1.80 [95% confidence interval (CI) 1.54–2.1] and 1.78 (95% confidence interval 1.56–2.04), respectively, although the apparent heterogeneity of the included studies was detected. In subgroup analysis, cohorts of severe and mild patients of COVID-19 assessed in Europe had a significant pooled weighted mean difference of 6.61 mmHg (95% CI 3.66–9.55) with no heterogeneity found (p = 0.26). The genes in the shared signature of hypertension and the COVID-19 severity were mostly expressed in lungs. Analysis of molecular networks commonly affected both by hypertension and by severe COVID-19 highlighted CCR1/CCR5 and IL10RB signaling, as well as Th1 and Th2 activation pathways, and also a potential for a shared regulation with multiple sclerosis.Conclusion: Hypertension is significantly associated with the severe course of COVID-19. Genetic variants within inflammation- and immunity-related genes may affect their expression in lungs and confer liability to both elevated blood pressure and to severe COVID-19.

Abstract Negative life events (NLEs) are an important predictor of depressive symptoms (DS). College students experiencing NLEs are at risk of developing DS that could further weaken their academic engagement (AE), while social supports may assuage such negative effect. The aim of this study was to examine the relationship between negative life events, depressive symptoms, and academic engagement, and how the NLE-DS-AE relationship is affected by the level of social support among Chinese college students. To test this hypothesis, we applied data from the Decoding Happiness Gene Cohort Study (DHGCS). Baseline depressive symptoms and academic engagement were measured at the beginning of the first academic year. Approximately 12 months later, negative life events and social support over the past year were assessed retrospectively along with current depressive symptoms and academic engagement. A total of 3629 college students (Age = 18.67 ± 0.82) were included in the study. The prevalence of depressive symptoms was 26.7% and 36.7% in college students at the beginning of the first and second academic year, respectively. Depressive symptoms predicted subsequent academic engagement rather than the reverse based on cross-lagged analyses. Using structural equation modeling analyses, findings revealed a partial mediation effect of social support between negative life events and the development of depressive symptoms, and a partial mediation effect between negative life events and academic engagement. The findings presented negative life events jeopardize the academic engagement via depressive symptoms, while social supports are able to cancel such negative effect among college students under the Chinese cultural context.

Abstract Background Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). Methods A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). Results The authors identified several novel loci reaching the threshold of genome-wide significance level (P

Abstract To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and quality assessment were performed in duplicate. A total of 51 eligible studies were included in the systematic review, and data from 12 (4182 subjects) were extracted for meta-analysis regarding the following 2 domains: (1) serum matrix metallopeptidase-7 (MMP-7), interleukin33 (IL-33) and γ-glutamyl transferase (GGT) to differentiate BA from non-BA; (2) the aspartate aminotransferase to platelet ratio index (APRi) to predict post-KPE liver fibrosis/cirrhosis. The summary sensitivity, specificity and area under the curve (AUC) of MMP-7 for diagnosing BA were 96%, 91% and 0.9847, respectively, and those of GGT were 80%, 79% and 0.9645, respectively. The summary sensitivity and specificity of IL-33 for diagnosing BA were 77% and 85%, respectively. The summary sensitivity and specificity of APRi for predicting post-KPE liver fibrosis were 61% and 80%, respectively, and the summary sensitivity, specificity and AUC of APRi for predicting post-KPE cirrhosis were 78%, 83% and 0.8729, respectively. Moreover, good evidence was shown in investigations of serum IL-18 and IL-33 in distinguishing BA from healthy controls, serum IL-18 for prognosis of post-KPE persistent jaundice, and serum hyaluronic acid and MMP-7 for prognosis of post-KPE significant liver fibrosis. MMP-7, IL-33 and GGT are useful biomarkers to assist in the diagnosis of BA. APRi might be used to predict post-KPE significant liver fibrosis and cirrhosis. These noninvasive biomarkers can be integrated into the management protocol of BA.

Hypoxia and reoxygenation (H/R) play a prevalent role in heart-related diseases. Histone demethylases are involved in myocardial injury. In this study, the mechanism of the lysine-specific histone demethylase 1A (KDM1A/LSD1) on cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury (MIRI) was investigated. Firstly, HL-1 cells were treated with H/R to establish the MIRI models. The expressions of KDM1A and Sex Determining Region Y-Box Transcription Factor 9 (SOX9) in H/R-treated HL-1 cells were examined. The cell viability, markers of myocardial injury (LDH, AST, and CK-MB) and apoptosis (Bax and Bcl-2), and Caspase-3 and Caspase-9 protein activities were detected, respectively. We found that H/R treatment promoted cardiomyocyte apoptosis and downregulated KDM1A, and overexpressing KDM1A reduced apoptosis in H/R-treated cardiomyocytes. Subsequently, tri-methylation of lysine 4 on histone H3 (H3K4me3) level on the SOX9 promoter region was detected. We found that KDM1A repressed SOX9 transcription by reducing H3K4me3. Then, HL-1 cells were treated with CPI-455 and plasmid pcDNA3.1-SOX9 and had joint experiments with pcDNA3.1-KDM1A. We disclosed that upregulating H3K4me3 or overexpressing SOX9 reversed the inhibitory effect of overexpressing KDM1A on apoptosis of H/R-treated cardiomyocytes. In conclusion, KDM1A inhibited SOX9 transcription by reducing the H3K4me3 on the SOX9 promoter region and thus inhibited H/R-induced apoptosis of cardiomyocytes.

ObjectiveThe pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking.DesignPatients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively.ResultsA total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea.ConclusionThe clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

Most face recognition methods rely on deep convolutional neural networks (CNNs) that construct multiple layers of processing units in a cascaded form and employ convolution operations to fuse local features. However, these methods are not conducive to modeling the global semantic information of the face and lack attention to important facial feature regions and their spatial relationships. In this work, a Group Depth-Wise Transpose Attention (GDTA) block is designed to effectively capture both local and global representations, mitigate the issue of limited receptive fields in CNNs, and establish long-range dependencies among different feature regions. Based on GDTA and CNNs, a novel, efficient, and lightweight face recognition model called CFormerFaceNet, which combines a CNN and Transformer, is proposed. The model significantly reduces the parameters and computational cost without compromising performance, greatly improving the computational efficiency of deep neural networks in face recognition tasks. The model achieves competitive accuracy on multiple challenging benchmark face datasets, including LFW, CPLFW, CALFW, SLLFW, CFP_FF, CFP_FP, and AgeDB-30, while maintaining the minimum computational cost compared to all other advanced face recognition models. The experimental results using computers and embedded devices also demonstrate that it can meet real-time requirements in practical applications.

Shipping Enterprise Credit Named Entity Recognition (NER) aims to recognize shipping enterprise credit entities from unstructured shipping enterprise credit texts. Aiming at the problem of low entity recognition rate caused by complex and diverse entities and nesting phenomenon in the field of shipping enterprise credit, a deep learning method based on multi-feature fusion is proposed to improve the recognition effect of shipping enterprise credit entities. In this study, the shipping enterprise credit dataset is manually labeled using the BIO labeling model, combining the pre-trained model Bidirectional Encoder Representations from Transformers (BERT) and bidirectional gated recurrent unit (BiGRU) with conditional random field (CRF) to form the BERT-BiGRU-CRF model, and changing the input of the model from a single feature vector to a multi-feature vector (MF) after stitching character vector features, word vector features, word length features, and part-of-speech (pos) features; BiGRU is introduced to extract the contextual features of shipping enterprise credit texts. Finally, CRF completes the sequence annotation task. According to the experimental results, using the BERT-MF-BiGRU-CRF model for NER of shipping enterprise credit text data, the F1 Score (F1) reaches 91.7%, which is 8.37% higher than the traditional BERT-BiGRU-CRF model. The experimental results show that the BERT-MF-BiGRU-CRF model can effectively perform NER for shipping enterprise credit text data, which is helpful to construct a credit knowledge graph for shipping enterprises, while the research results can provide references for complex entities and nested entities recognition in other fields.

The improvement of data-driven soft sensor modeling methods and techniques for the industrial process has strongly promoted the development of the intelligent process industry. Among them, ensemble learning is an excellent modeling framework. Accuracy and diversity are two key factors that run through the entire stage of building an ensemble learning-based soft sensor. Existing base model generating methods or ensemble pruning methods always consider the two factors separately, which has limited the development of high-performance but low-complexity soft sensors. To work out this issue, a selective ensemble learning-based soft sensor modeling method based on multi-kernel latent variable space and evolutionary multi-objective optimization is proposed, referred to as MOSE-MLV-VSPLS. This method designs a multiple diversity enhancement mechanism in the base model generation stage. Diversified input variable subspaces are first constructed using the maximum information coefficient on the bootstrapping random resampling subset. Then a set of base models that combine accuracy and diversity are generated on supervised latent variable subspaces under multiple kernel function perturbations. Further, two quantifiable parameters are designed for accuracy and diversity, and the multi-objective gray wolf optimization algorithm is used to select the base models that maximize these two important parameters to achieve effective ensemble pruning at the model ensemble stage. The MOSE-MLV-VSPLS method is applied to two typical industry processes, and the experimental results show that the method is effective and superior in selective ensemble-based soft sensor modeling.

Abstract Background The upsurge in HIV infections among students is a matter of particular concern. However, few studies have explored the epidemiological characteristics including the risky sexual networking of HIV-infected students in Zhejiang province, China. Methods Using the provincial surveillance data of HIV-infected students, we conducted a retrospective epidemiology study to describe the epidemiological characteristics of 628 newly diagnosed cases from 2011 to 2016 and detailed information of 124 cases from 2015 to 2016. Spatial analyses were conducted using ArcGIS software, and statistical analyses were performed using SPSS software. Results A total of 628 cases of HIV/AIDS were diagnosed among students in Zhejiang Province, China between 2011 and 2016. The cases showed an overall increasing trend over time, while the proportions of students with HIV disease status, cases diagnosed by HIV voluntary counseling and testing (VCT), and cases of homosexual transmission remained stable over time. Significant spatial heterogeneity in the cases was seen at the county level. Detailed data on 124 HIV-positive individuals collected from the local Center for Disease Control and Prevention (CDC) from 2015 and 2016, showed that the majority of them (85.5%,) engaged in homosexual behavior, and 93.4% had sex with casual partners. These partners included not only social members, but also other students. Online dating applications represented the most common means of seeking and communicating with homosexual partners. The level of awareness regarding the risk of HIV infection, and the amount coverage of face-to-face education towards students were both low. Conclusions HIV infections among students were characterized by increasing trend and spatial clustering in Zhejiang Province between 2011 and 2016, with homosexual sexual activity being the main mode of infection. Interventions are urgently required to prevent HIV infection in this population by increasing awareness of the disease. HIV testing programs and information regarding disease prevention specifically through online dating applications are needed.

Human epidermal growth factor receptor 2 (HER2) positive (+) classical type invasive lobular carcinoma (cILC) of the breast is extremely rare and its clinicopathologic features have not been well characterized. We compared features of HER2(+) and HER2 negative (−) cILCs. A total of 29 cases were identified from the clinical database at our institution from 2011-2019; 9 were HER2(+) cILC tumors and 20 were HER2(−) cILC tumors. The results reveal that HER2(+) cILC group had significantly increased Ki-67 expression and reduced estrogen receptor (ER) expression compared to HER2(−) cILC group (both p < 0.05). In addition, HER2(+) cILCs tended to be diagnosed at a younger age and more common in the left breast, and appeared to have a higher frequency of nodal or distant metastases. These clinicopathologic features suggest HER2(+) cILC tumors may have more aggressive behavior than their HER2(−) counterpart although both groups of tumors showed similar morphologic features. Future directions of the study: (1) To conduct a multi-institutional study with a larger case series of HER2(+) cILC to further characterize its clinicopathologic features; (2) to compare molecular profiles by next generation sequencing (NGS) assay between HER2(+) cILC and HER2(−) cILC cases to better understand tumor biology of this rare subset of HER2(+) breast cancer; and (3) to compare molecular characteristics of HER2(+) cILC and HER2(+) high grade breast cancer in conjunction with status of tumor response to anti-HER2 therapy to provide insight to management of this special type of low grade breast cancer to avoid unnecessary treatment and related toxicity

The fungal genus Alternaria was distributed widely and found in different habitats such as plant or indoor environment. During an investigation into this genus in China, two new Alternaria species, Alternaria vulgarae and A. divaricatae were respectively isolated from diseased leaves of Foeniculum vulgare and Saposhnikovia divaricata, which both belonged to Umbelliferae. Phylogenetically, they were determined as new species belonging in the section Radicina of Alternaria based on the combined four gene fragments of ITS, TEF1, GAPDH and RPB2. Morphologically, the two species were illustrated and compared with other relevant Alternaria species in section Radicina.

DiGeorge Syndrome Critical Region Gene 8 (DGCR8) is a key component of the microprocessor complex governing the maturation of most microRNAs, some of which participate in schizophrenia and neural development. Previous studies have found that the 22q11.2 locus, containing DGCR8, confers a risk of schizophrenia. However, the role of DGCR8 in schizophrenia and the early stage of neural development has remained unknown. In the present study, we try to identify the role of DGCR8 in schizophrenia from human samples and animal models. We found that the G allele and GG genotype of rs3757 in DGCR8 conferred a higher risk of schizophrenia, which likely resulted from higher expression of DGCR8 according to our test of dual-luciferase reporter system. Employed overexpression model in utero and adult mice, we also revealed that the aberrant increase of Dgcr8 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice. Together, these results demonstrate that DGCR8 may play a role in the etiology of schizophrenia through regulating neural development.

IntroductionLupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis.MethodsTo characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein–protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology/Renal Pathology Society (ISN/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software.ResultsA total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell–cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV.ConclusionsThe DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.

BackgroundPleural cryobiopsy is a novel technique for the diagnosis of pleural pathologies. However, the safety and feasibility of this modality compared to standard forceps for pleural biopsy has not been fully elucidated. This systematic review and meta-analysis aims to establish the efficacy and safety of cryobiopsy for evaluation of undiagnosed pleural effusion.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and Web of science databases up to December 16, 2021 to identify relevant articles. We included randomized controlled trials, cohort studies, retrospectives studies and case series that compared pleural cryobiopsy and forceps biopsy. A qualitative assessment was performed using the QUADAS-2 tool.ResultsOf the 365 articles identified by our search, 15 studies were eligible for inclusion. The specimen sizes obtained with cryobiopsy were significantly larger compared with forceps biopsy (Standard mean difference 1.16; 95 % CI: 0.51–1.82; P < 0.01). Furthermore, the cryobiopsy tissue specimens were deeper (OR 2.68; 95 % CI: 1.39–5.16; P < 0.01) and qualitatively better with less crush artifacts (OR 0.06; 95 % CI: 0.01–0.26; P < 0.01). There was no significant difference in diagnostic yield (OR 1.32; 95 % CI: 0.79–2.21; P = 0.29) and mild to moderate bleeding events (OR 1.21; 95 % CI: 0.64–2.29; P = 0.57) between pleural cryobiopsy and forceps biopsy. No publication bias was observed among these studies.ConclusionsCompared to flexible forceps biopsy pleural cryobiopsy obtained larger and deeper tissue specimens with less crush artifacts but does not show superiority for diagnostic yield. Further studies are still needed to verify these findings.

The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. All 24 Env-pseudotyped viruses were resistant to bNAbs 2G12, PGT121, and PGT135. The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.

Abstract Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE−/−) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE−/− mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

The aim of this study was to evaluate the performance of an assay using dried plasma spot (DPS) and dried blood spot (DBS) samples for the serological detection of anti-hepatitis C virus (HCV) antibodies. Between January and July 2019, plasma, DPS and DBS specimens were collected from individuals at high-risk for HCV infection. Samples were tested for anti-HCV by ELISA, and the performance of DPS and DBS specimens was examined using results from the plasma testing, as the standard. Blood samples were collected from 329 persons, including 129 men who have sex with men and 200 intravenous drug users. Results from the plasma testing indicated that 118 samples (59.0%) were HCV positive. Data from the DPS sample testing showed sensitivity as 99.2% (95% confidence interval [CI]: 0.95–1.00) and specificity as 100% (95% CI: 0.98–1.00) for HCV detection, with Kappa of 99.3% (95% CI: 0.98–1.00) while in DBS sample testing the sensitivity as 98.3% (95% CI: 0.93–1.00) and specificity as 100% (95% CI: 0.98–1.00), with Kappa of 98.7% (95% CI: 0.97–1.00), respectively. Spearman’s correlation coefficients for the comparisons between plasma and DPS specimen, plasma and DBS specimens, DPS and DBS specimens were 0.857, 0.750, and 0.739, respectively. Compared with the results in plasma, 1 sample was not detected using the DPS specimens, and 2 samples were failed for the positive detection, using the DBS specimens. Both DPS and DBS samples were promising alternatives to plasma, for the detection of anti-HCV antibodies.

Abstract Background and objective Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach. Methods The putative ingredients of ginger and its related targets were discerned from the TCMSP and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger. Results Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation. Conclusion This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

AIM: To analyze the protective effect of resveratrol on the optic nerve of glaucoma rats and its effect on the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)signal pathway and its related factors.METHODS: SPF grade SD rats were used to cauterize the scleral surface veins to make a right eye glaucoma model. After successful modeling, different doses(10, 20, 40 mg/kg intraperitoneal injection)of resveratrol were used to intervene. Intraocular pressure was measured 2h after the last administration, and retinal slices were made to observe the survival of retinal ganglion cells(RGC). Retinal plaque to observe the survival of retinal ganglion cells(RGC). Real-time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression of retinal PI3K, Akt, basic fibroblast growth factor(bFGF), and brain-derived neurotrophic factor(BDNF).RESULTS: The intraocular pressure(30.25±4.25)mmHg in the model group was higher than that in the low-dose group(26.30±4.05)mmHg, the middle dose group(22.31±3.68)mmHg and the high dose group(18.32±3.21)mmHg, and the model group RGC labeling rate(48.25±4.50)% was lower than the low dose group(56.32±5.05)%, middle dose group(66.03±6.68)% and high dose group(78.56±7.82)%(P

Influenza A(H1N1)pdm09 virus has remained in a seasonal circulation since being recognized in 2009. Although it followed a mild course in most patients, in others it caused a series of severe clinical illnesses. Epidemiologic studies have implicated that host factors have a major influence on the disease severity of influenza A(H1N1)pdm09 infection. However, an understanding of relevant genetic variations and the underlying mechanisms is still limited. In this present study, we used a host-based whole genome sequencing (WGS) method to comprehensively explore the genetic risk loci associated with severity of influenza A(H1N1)pdm09 infection. From the common single-nucleotide variants (SNVs) analysis, we identified the abnormal nominally significant (P < 1 × 10−4) common SNVs enriched in PTBP3 gene. The results of rare functional SNVs analysis supported that there were several novel candidate genes might confer risk of severe influenza A(H1N1)pdm09 diseases, such as FTSJ3, CPVL, BST2, NOD2 and MAVS. Moreover, our results of gene set based analysis indicated that the HIF-1 transcription factor and IFN-γ pathway might play an important role in the underlying mechanism of severe influenza A(H1N1)pdm09. These findings will increase our knowledge about biological mechanism underlying the severe influenza A(H1N1)pdm09 and facilitate to design novel personalized treatments.

Abstract Background There is now ample evidence suggesting that extracorporeal shock wave therapy (ESWT) can improve hip mobility and reduce pain in patients with osteonecrosis of the femoral head (ONFH). The ability of ESWT to cure bone marrow edema syndrome (BMES) in patients with ONFH, 12 weeks after the initial course of ESWT, needs to be verified further and more relevant clinical research-based evidence should be consolidated. This study aimed to evaluate the efficacy of ESWT for BMES caused by ONFH. Methods This retrospective cohort study included 67 patients with BMES caused by ONFH who were participating in a rehabilitation program as outpatients. Before and after ESWT, the area of femoral bone marrow edema was evaluated by magnetic resonance imaging (MRI), and the Harris score and Charnley score were evaluated as hip pain and function indicators. Results After ESWT, MRI revealed that the area of bone marrow edema decreased from 984.6 ± 433.2 mm2 to 189.7 ± 214.4 mm2 (P < 0.0001). The Harris score increased from 42.2 ± 9.1 to 77.7 ± 10.8 points (P < 0.0001). The Charnley score increased from 7.3 ± 1.4 to 12.0 ± 1.7 (P < 0.0001). ESWT was effective in treating BMES in 98.5% of the cases. Conclusions This study demonstrated that ESWT can effectively treat BMES caused by ONFH and can aid in pain relief and functional recovery in patients with ONFH. Thus, ESWT should be included in the classic physical therapy regimen for patients with ONFH and BMES.

The respiratory burst oxidase homolog (RBOH), as the key producer of reactive oxygen species (ROS), plays an essential role in plant development. In this study, a bioinformatic analysis was performed on 22 plant species, and 181 RBOH homologues were identified. A typical RBOH family was identified only in terrestrial plants, and the number of RBOHs increased from non-angiosperms to angiosperms. Whole genome duplication (WGD)/segmental duplication played a key role in RBOH gene family expansion. Amino acid numbers of 181 RBOHs ranged from 98 to 1461, and the encoded proteins had molecular weights from 11.1 to 163.6 kDa, respectively. All plant RBOHs contained a conserved NADPH_Ox domain, while some of them lacked the FAD_binding_8 domain. Plant RBOHs were classified into five main subgroups by phylogenetic analysis. Most RBOH members in the same subgroup showed conservation in both motif distribution and gene structure composition. Fifteen ZmRBOHs were identified in maize genome and were positioned in eight maize chromosomes. A total of three pairs of orthologous genes were found in maize, including ZmRBOH6/ZmRBOH8, ZmRBOH4/ZmRBOH10 and ZmRBOH15/ZmRBOH2. A Ka/Ks calculation confirmed that purifying selection was the main driving force in their evolution. ZmRBOHs had typical conserved domains and similar protein structures. cis-element analyses together with the expression profiles of the ZmRBOH genes in various tissues and stages of development suggested that ZmRBOH was involved in distinct biological processes and stress responses. Based on the RNA-Seq data and qRT-PCR analysis, the transcriptional response of ZmRBOH genes was examined under various abiotic stresses, and most of ZmRBOH genes were up-regulated by cold stress. These findings provide valuable information for further revealing the biological roles of ZmRBOH genes in plant development and abiotic stress responses.

The utilization of mountain wind resources are important issues in the development of wind energy. However, when wind flows over mountainous terrain, its velocity and direction undergo certain changes, resulting in more complex mountain wind fields and induced structural wind effects. To study the distribution characteristics of horizontal wind in mountainous areas, in this study, wind tunnel experiments were conducted on regular mountain models with different slopes to investigate the wind field characteristics at various locations in the mountain range. The research shows that near the mountain surface, the wind speed and velocity ratio follow the order of mountain top > mountain waist > mountain foot, with a wind acceleration effect at the mountain top (wind speed ratio greater than 1) and a wind deceleration effect at the mountain foot and waist (wind speed ratio less than 1). As the height increases, the wind speed ratios gradually approach 1. Moreover, with an increase in slope ratio, the wind speed decreases at the mountain foot and increases at the mountain top. And with the increase of the slope leads to an increasing difference in wind speed ratio between the mountain top and the foot.

High-resolution X-ray observations offer a unique tool for probing the still-elusive connection between galaxy mergers and active galactic nuclei (AGNs). We present an analysis of nuclear X-ray emission in an optically selected sample of 92 close galaxy pairs (with projected separations ≲20 kpc and line-of-sight velocity offsets 10 ^41 erg s ^−1 ), the detection rate becomes $18{ \% }_{-3 \% }^{+3 \% }$ (32/184), which shows no excess compared to the X-ray detection rate of a comparison sample of optically classified single AGNs. The fraction of pairs containing dual AGN is only $2{ \% }_{-2 \% }^{+2 \% }$ . Moreover, most nuclei at the smallest projected separations probed by our sample (a few kiloparsecs) have an unexpectedly low apparent X-ray luminosity and Eddington ratio, which cannot be solely explained by circumnuclear obscuration. These findings suggest that close galaxy interaction is not a sufficient condition for triggering a high level of AGN activity.

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells.

With the advancement of technology and the rise of the unmanned aerial vehicle industry, the use of drones has grown tremendously. For drones performing near-ground delivery missions, the problem of 3D space-based path planning is particularly important in the autonomous navigation of drones in complex spaces. Therefore, an improved butterfly optimization (BOA-TSAR) algorithm is proposed in this paper to achieve the autonomous pathfinding of drones in 3D space. First, this paper improves the randomness strategy of the initial population generation in the butterfly optimization algorithm (BOA) via the Tent chaotic mapping method, by means of the removal of the short-period property, which balances the equilibrium of the initial solutions generated by the BOA algorithm in the solution space. Secondly, this paper improves the shortcomings of the BOA algorithm in terms of slower convergence, lower accuracy, and the existence of local optimal stagnation when dealing with high-dimensional complex functions via adaptive nonlinear inertia weights, a simulated annealing strategy, and stochasticity mutation with global adaptive features. Finally, this paper proposes an initial population generation strategy, based on the 3D line of sight (LOS) detection method, to further reduce the generation of path interruption points while ensuring the diversity of feasible solutions generated by the BOA algorithm for paths. In this paper, we verify the superior performance of BOA-TSAR by means of simulation experiments. The simulation results show that BOA-TSAR is very competitive among swarm intelligence (SI) algorithms of the same type. At the same time, the BOA-TSAR algorithm achieves the optimal path length measure and smoothness measure in the path-planning experiment.

Abstract Background To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition function of patients with Parkinson’s disease (PD) and to estimate which cognitive function may obtain more benefits from rTMS. Method The articles dealing with rTMS on cognitive function of PD patients were retrieved from the databases until April 2019. Outcomes of global cognitive function and different cognitive domains were extracted. The standardized mean differences (SMDs) with 95% confidence interval (CI) of cognitive outcome for different parameters, scales, and cognitive functions were estimated. Results Fourteen studies involving 173 subjects were included in this meta-analysis. A significant effect size was observed with the mini-mental state examination (MMSE) for the global cognitive outcome based on the evidence of four published articles. Further subtests for different cognitive domains demonstrated prominent effect for the executive function. The significant effect sizes for executive function were found with multiple sessions of high-frequency rTMS over frontal cortex; especially over dorsolateral prefrontal cortex (DLPFC). All of the other cognitive domains, which included memory, attention, and language ability, did not obtain significant effects. Conclusions Multiple sessions of high-frequency rTMS over the DLPFC may have positive effect on executive function in PD patients. Further well designed studies with large sample sizes are needed to verify our results and ascertain the long-term effects of rTMS.

Abstract Background To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. Methods Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. Results Twenty-two eligible clinical trials including 15,676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89–0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89–0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99–1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19–13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40–3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95–5.06) and TN (pooled OR, 4.09; 95% CI, 2.71–6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83–2.04). Conclusions The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

Abstract Background To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. Methods The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. Results Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74–3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87–4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72–4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43–4.77), 1-year (pooled OR = 2.96; 95% CI 1.71–5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18–2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33–0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28–10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05–1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84–2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69–4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. Conclusion The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.

Polymorphisms in the oxytocin receptor (OXTR) gene are related to individual differences in negative emotions, such as depressive symptoms and anxiety. However, it remains unclear what the potential roles of OXTR polymorphisms are in subjective well-being (SWB), which is negatively correlated with depressive symptoms. We examined attributional styles as mediator between SWB and five polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298, rs1042778, rs2268494, and rs2268490) among 627 full-time college freshmen (Mage = 20.90, SD = 0.82 for male; Mage = 20.81, SD = 0.92 for female) using structural equation modeling. The results showed that individuals with the OXTR rs2254298 AA genotype and rs53576 AA/GA genotype reported higher scores on SWB, which suggested that individuals with this genotype experienced more happiness. Moreover, external attributional style partially mediated the association between OXTR rs2254298 polymorphism and SWB (β = 0.019, 95%CI [0.001, 0.036], p = 0.035). In conclusion, our findings demonstrated that the genetic variations of OXTR played a role in the individual differences of SWB, and external attribution style could mediate the association.

We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1-2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2-80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2-52, n = 523), 2 (2-80, n = 256), and 3 (2-6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168-1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AIage = 0.090, P

Black phosphorus (BP) consists of phosphorus atoms, an essential element of bone and nucleic acid, which covalently bonds to three adjacent phosphorus atoms to form a puckered bilayer structure. With its anisotropy, band gap, biodegradability, and biocompatibility properties, BP is considered promising for cancer therapy. For example, BP under irradiation can convert near-infrared (NIR) light into heat and reactive oxygen species (ROS) to damage cancer cells, called photothermal therapy (PTT) and photodynamic therapy (PDT). Compared with PTT and PDT, the novel techniques of sonodynamic therapy (SDT) and photoacoustic therapy (PAT) exhibit amplified ROS generation and precise photoacoustic-shockwaves to enhance anticancer effect when BP receives ultrasound or NIR irradiation. Based on the prospective phototherapy, BP with irradiation can cause a “double-kill” to tumor cells, involving tumor-structure damage induced by heat, ROS, and shockwaves and a subsequent anticancer immune response induced by in situ vaccines construction in tumor site, which is referred to as photoimmunotherapy (PIT). In conclusion, BP shows promise in natural antitumor biological activity, biological imaging, drug delivery, PTT/PDT/SDT/PAT/PIT, nanovaccines, nanoadjuvants, and combination immunotherapy regimens.

Supply chain management is critical for addressing uncertainties caused by random demand and production yield. In this study, a random yield supply chain, in which the production process of fresh agricultural products is easily affected by factors, such as weather, soil, or plant diseases and insect pests, was considered. Therefore, the actual output is typically less than the planned output. A model in which the producer faces yield uncertainty was considered, and the influence of the producer’s fairness concerns on the planned output of the contract-farming supply chain was considered. Methods to motivate the producer to increase planned output through reasonable contracts were investigated. The results revealed that the producer’s fairness concern considerably influences the optimal expected profit. In the case of the random output, the planned output and maximum expected profits reduce when the farmer exhibits fairness concerns. As the degree of the producer’s fairness concern increases, the planned output and expected profit gradually decrease The cost-sharing contract can effectively encourage the producer to increase his planned output and expected utility. Finally, the results were verified numerically.

Excessive vibration of temporary grandstand by the crowd has lateral rhythmic motions, which attracted increasing attention in the recent years. This paper focuses on experiments where a temporary grandstand occupied by 20 participants is oscillated by a shaking table with a series of random waves and the crowd-induced rhythmic swaying motions at lateral direction, respectively. The dynamic forces that were induced by participants who have swayed at 0.5–1.8 Hz are recorded by a tri-axial human biomechanics force plate. A new relationship between the annoyance rate and structural acceleration at logarithmic coordinate is investigated and proposed, and the swaying load model is given. Based on these experimental results, a simplified three-degree-of-freedom lumped dynamic model of the joint human–structure system is reinterpreted. Afterwards, combined with a feasible range of crowd/structural dynamic parameters, a series of interaction models are analyzed, the vibration dose value (VDV) of the structure is obtained and discussed, and the notable parameters for interaction model are predicted. The experimental results show that the lateral serviceability limit is 1.29 m/s1.75 and the upper boundary is 2.32 m/s1.75. The dynamic response of model indicated that the VDV of structure will be decreased with increasing the mass of static crowd and damping ratio of the dynamic crowd. The max response of the model is α ≤ 0.6, f2 = 1.8 Hz or α > 0.6, f2 = 1.5 Hz or f1 = 2.5–3.5 Hz. It may be used as a reference value in vibration safety and serviceability assessment of TDGs, to estimate realistically the vibration response on the occasions when the crowds are swaying.

BackgroundThis study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS).MethodsThe messenger RNA (mRNA) levels of 770 immune-related genes were detected using a NanoString nCounter platform. To verify the NanoString results, quantitative analysis of nine gene mRNAs was performed using real-time RT-PCR in more samples.ResultsFirstly, compared with the steroid-sensitive nephrotic syndrome (SSNS) group (n=3), significant changes were observed in the mRNA level of 70 genes, including MAP3K14, CYBA, SLC3A2, CREB-binding protein (CREBBP), CD68, forkhead box P1 (FOXP1), CD74, ITGB2, IFI30, and so forth, in the SRNS group (n=3). A total of 129 children with idiopathic nephrotic syndrome (INS), 15 with acute glomerulonephritis, and 6 with immunoglobulin A nephropathy (IgAN) were enrolled to verify the NanoString results. Compared with patients with IgAN, those with INS had significantly lower levels of FOXP1 (P=0.047) and higher levels of CREBBP (P=0.023). Among SSNS, the mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups (P=0.006). Compared with the SSNS group, CREBBP was significantly elevated in the SRNS group (P=0.02). Further, CYBA significantly decreased in the SRNS group (P=0.01). The area under the curve (AUC) for CREBBP and CYBA was 0.655 and 0.669, respectively. CREBBP had a sensitivity of 83.3% and a specificity of 49.4% and CYBA had a sensitivity of 58.3% and a specificity of 83.1% to rule out SSNS and SRNS. The diagnosis value was better for CREBBP+CYBA than for CREBBP or CYBA alone, indicating that the combination of CREBBP and CYBA was a more effective biomarker in predicting steroid resistance (AUC=0.666; sensitivity=63.9%; specificity=76.4%).ConclusionsThis study was novel in investigating the urinary sediment mRNA level in children with INS using high-throughput NanoString nCounter technology, and 70 genes that may relate to SRNS were found. The results revealed that the urinary sediment mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups. Meanwhile, CREBBP was significantly elevated and CYBA was significantly lowered in the SRNS group compared with the SSNS group.

Countermovement jump (CMJ) is used to assess athletic performance of the lower limbs. Drop jump (DJ) is an effect training method that can improve athlete’s jumping performance. The main purpose of this study is to explore the effects of different drop jump heights (DJH)30, DJH40, and DJH50 cm for 250 drop jumps (DJs250) on CMJ. Eighteen male athletes were selected as subjects. After the 50th, 100th, 150th, 200th, and 250th DJs, perform 5 groups of CMJ (the average of 3 times for each group) and record them as the 50th, 100th, 150th, 200th, and 250th CMJ jumps (CMJs50, CMJs100, CMJs150, CMJs200, and CMJs250). The BTS motion capture system and two force plates are used to record data. The MATLAB software was used to analyze data through one-way ANOVA repeated measures. If there is a significant difference, the LSD method is used for post hoc comparison. Jump height (JH), contact time (CT), reaction intensity index (RSI), average rate of force development (ARFD), left average rate of force development (LARFD), and right average rate of force development (RARFD) of CMJs50, CMJs100, CMJs150, and CMJs200 at DJH50 were greater than those at DJH40 and DJH30 (all p

Objectives To evaluate the diagnostic yield and safety of brainstem stereotactic biopsy for brainstem lesions. Methods We performed a meta-analysis of English articles retrieved from the PubMed, Web of Science, Cochrane Library, and APA psycInfo databases up to May 12, 2021. A binary fixed-effect model, the inverse variance method, or a binary random-effect model, the Dersimonian Laird method, were utilized for pooling the data. This meta-analysis was registered with INPLASY, INPLASY202190034. Findings A total of 41 eligible studies with 2792 participants were included. The weighted average diagnostic yield was 97.0% (95% confidential interval [CI], 96.0-97.9%). The weighted average proportions of temporary complications, permanent deficits, and deaths were 6.2% (95% CI, 4.5–7.9%), .5% (95% CI, .2–.8%), and .3% (95% CI, .1–.5%), respectively. The subgroup analysis indicated a nearly identical weighted average diagnostic yield between MRI-guided stereotactic biopsy and CT-guided stereotactic biopsy (95.9% vs 95.8%) but slightly increased proportions of temporary complications (7.9% vs 6.0%), permanent deficits (1.9% vs .2%), and deaths (1.1% vs .4%) in the former compared to the latter. Moreover, a greater weighted average diagnostic yield (99.2% vs 97.6%) and lower proportions of temporary complications (5.1% vs 6.8%) and deaths (.7% vs 1.5%) were shown in the pediatric patient population than in the adult patient population. Conclusions Brainstem stereotactic biopsy demonstrates striking accuracy plus satisfying safety in the diagnosis of brainstem lesions. The diagnostic yield, morbidity, and mortality mildly vary based on the diversity of assistant techniques and subject populations.

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), as an emerging pollutant, was often detected in the aquatic environments, but the chemical behavior and potential eco-toxicity of each stereoisomer are poorly understood. Here, the chemical behavior of TBECH stereoisomers under the oxidation of ROS (OH· and HO2·) in the aqueous phase was investigated by computational chemistry. Besides, the eco-toxicity effects of TBECH and representative transformation products were obtained by computational toxicology. In the natural environments, TBECH stereoisomers could be transformed under the initiation of ROS, and the key oxidation species is OH· rather than HO2· in this process. DOM could indirectly promote the transformation of TBECH stereoisomers, resulting in the half-life (t1/2) of TBECH stereoisomers in less than 180 days, thus no longer maintaining environmental persistence. Although TBECH stereoisomers may show environmental persistence in natural waters, AOPs based on OH· could bring about their rapid transformation, which predicts the effectiveness of OH-based AOPs for the treatment of TBECH wastewater. The results of the eco-toxicity assessment showed that the transformation of TBECH stereoisomers is beneficial to the reduction of toxicity, but the transformation products are not completely harmless. Thus, it is urgent to clarify the environmental behaviors and risks of these transformation products that remain toxic in the aquatic environments.

Abstract Nanomaterials having hetero‐metallic junctions are being explored for sensing, catalytic, and biomedical applications. Insight into the bimetallic junction at nanoscale is important from both fundamental and application perspectives. In this study, we synthesized segmented Au–Ag wire by sequentially electroplating Au and Ag in cylindrical pores in anodic alumina membrane filters. We probed the one photon, two photon, and second harmonic signal in Au–Ag wire at single particle level by focusing laser beam to a diffraction limited spot using a home‐built sample scanning type micro‐spectrometer. When exciting the Au–Ag junctions into the mid‐UV range using two‐photon excitation, we observed two luminescence peaks at 455 and 520 nm, respectively, possibly because of the surface plasmon resonances supported by the sharp boundary and granular nanostructures on the Au–Ag interface. Interestingly, we also observed intense second harmonic generation (SHG) signal from the junction with a yield more than two orders of magnitude higher than that from the Au tips. The SHG intensity as a function of excitation wavelength showed a similar trend to the two‐photon excited luminescence emission spectrum, indicating that the SHG signal was enhanced in the presence of optical resonances. The observation of enhanced radiative properties of the bimetallic junction in the suggested that the Au–Ag wire may serve as an excellent imaging probe or single particle sensors.

Multiple sclerosis (MS) is an autoimmune disease that leads to the demyelination of nerve axons. An increasing number of studies suggest that patients with MS exhibit altered metabolic profiles, which might contribute to the course of MS. However, the alteration of metabolic profiles in Chinese patients with MS and their potential roles in regulating the immune system remain elusive. In this study, we performed a global untargeted metabolomics approach in plasma samples from 22 MS-affected Chinese patients and 21 healthy subjects. A total of 42 differentially abundant metabolites (DAMs) belonging to amino acids, lipids, and carbohydrates were identified in the plasma of MS patients and compared with those in healthy controls. We observed an evident reduction in the levels of amino acids, such as L-tyrosine, L-isoleucine, and L-tryptophan, whereas there was a great increase in the levels of L-glutamic acid and L-valine in MS-affected patients. The levels of lipid and carbohydrate metabolites, such as sphingosine 1-phosphate and myo-inositol, were also reduced in patients with MS. In addition, the concentrations of proinflammatory cytokines, such as IL-17 and TNF-α, were significantly increased, whereas those of several anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-7, and MIP-1α, were distinctly reduced in the plasma of MS patients compared with those in healthy subjects. Interestingly, some DAMs, such as L-tryptophan and sphingosine 1-phosphate, showed an evident negative correlation with changes in the level of TNF-α and IL-17, while tightly positively correlating with altered concentrations of anti-inflammatory cytokines and chemokines, such as MIP-1α and RANTES. Our results revealed that altered metabolomic profiles might contribute to the pathogenesis and course of MS disease by modulating immuno-inflammatory responses in the peripheral system, which is essential for eliciting autoimmune responses in the central nervous system, thus resulting in the progression of MS. This study provides potential clues for developing therapeutic strategies for MS in the near future.

BackgroundIntraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts.Materials and MethodsWe conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate.ResultsA total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66–3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76–1.31), and OS (pooled OR = 0.95; 95% CI, 0.79–1.14) between the IORT cohort with the WBI cohort were both not statistically significant.ConclusionsDespite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.

Approximately 40% of rectal cancers during initial diagnosis are identified as locally advanced rectal cancers (LARCs), for which the standardized treatment scenario is total mesorectal excision following neoadjuvant chemoradiotherapy (nCRT). nCRT can lead to discernible reductions in local relapse rate and distant metastasis rate in LARC patients, in whom previously inoperable tumors may potentially be surgically removed. However, only 4% to 20% cases can attain pathological complete response, and the remaining patients who are unresponsive to nCRT have to suffer from the side effects plus toxicities and may encounter poor survival outcomes due to the late surgical intervention. As such, employing potential biomarkers to differentiate responders from nonresponders before nCRT implementation appears to be the overarching goal. Well-defined competing endogenous RNA (ceRNA) networks include long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA and circRNA-miRNA-mRNA networks. As ceRNAs, lncRNAs, and circRNAs sponge miRNAs to indirectly suppress miRNAs downstream of oncogenic mRNAs or tumor-suppressive mRNAs. The abnormal expression of mRNAs regulates the nCRT-induced DNA damage repair process through pluralistic carcinogenic signaling pathways, thereby bringing about alterations in the nCRT resistance/sensitivity of tumors. Moreover, many molecular mechanisms relevant to cell proliferation, metastasis, or apoptosis of cancers (eg, epithelial-mesenchymal transition and caspase-9-caspase-3 pathway) are influenced by ceRNA networks. Herein, we reviewed a large group of abnormally expressed mRNAs and noncoding RNAs that are associated with nCRT resistance/sensitivity in LARC patients and ultimately pinpointed the backbone role of ceRNA networks in the molecular mechanisms of nCRT resistance/sensitivity.

Vesicle associated membrane protein 2 (VAMP2) contains a conserved SNARE motif that interacts with syntaxin-1 and SNAP25 for SNARE complex assembly. Here authors use in-cell NMR spectroscopy to describe the dynamic membrane association of VAMP2 SNARE motif in mammalian cells at the atomic resolution.

Abstract Image fusion technology combines information from different source images of the same target and performs extremely effective information complementation, which is widely used for the transportation field, medicine field, and surveillance field. Specifically, due to the limitation of depth of field in imaging device, images cannot focus on all objects and miss partial details. To deal with this problem, an effective multi-focus image fusion method is proposed in this paper. We interpret the production of the focus map as a two-class classification task and solve this problem by using a method based on the cascade-forest model. Firstly, we extract the specific features from overlapping patches to represent the clarity level of source images. To obtain the focus map, feature vectors are fed into the pre-trained cascade-forest model. Then, we utilize consistency check to acquire the initial decision map. Afterward, guided image filtering is used for edge-reservation to refine the decision map. Finally, the result is obtained through pixel-wise weighted average strategy. Extensive experiments demonstrate that the proposed method achieves outstanding visual performance and excellent objective indicators.

Abstract Background To investigate the efficacy of neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET) and neoadjuvant chemoendocrine therapy (NCET) on the tumour response, including pathological complete response (pCR) rate and overall response rate (ORR), in postmenopausal women with hormone receptor (HR)-positive breast cancer. Methods Based on a PRISMA-IPD statement, the PubMed, Embase and Cochrane Library databases were used to identify eligible trials published from inception to 7 May 2019. Pooled odds ratio (OR) with 95% confidential interval (CI) was calculated to assess the pCR rate and ORR of tumours among those three treatments via fixed- or random-effect Mantel-Haenszel models in terms of a Heterogeneity Chi2 test with a significant level of p