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Abstract. Background:. Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). Methods:. We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. Results:. The abundance of fecal Veillonella parvula (V. parvula) decreased significantly after BBR administration (P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. Conclusion:. BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula, thereby blocking the development of colorectal tumors. Trial Registraion:. ClinicalTrials.gov, No. NCT02226185.

The study of morphological characteristics and growth information in fish scales is a crucial component of modern fishery biological research, while it has been less studied in fossil materials. This paper presents a detailed morphological description and growth analysis of a fossil ctenoid scale obtained from the Upper Cretaceous Campanian lacustrine deposits in northeastern China. The morphological features of this fossil scale are well-preserved and consistent with the structures found in ctenoid scales of extant fish species and display prominent ring ornamentation radiating outward from the central focus, with grooves intersecting the rings. A comparative analysis of the morphological characteristics between the fossil ctenoid scale and those well-studied extant fish Mugilidae allows us to explore the applicability of modern fishery biological research methods to the field of fossil scales. The scale length, scale width, the vertical distance from the focus to the apex of the scale, and the total number of radii have been measured. The age of the fish that possessed this ctenoid scale has been estimated by carefully counting the annuli, suggesting an age equal to or more than seven years. The distribution of growth rings on the scale potentially reflects the warm paleoclimatic condition and fish-friendly paleoenvironment prevalent during that period. This paper, moreover, serves as a notable application of fishery biological methods in the examination of fossil materials.

The seismic effects on sloped terrain, which are of paramount importance for engineering design and earthquake risk mitigation, have always been a central focus of earthquake engineering research. In this study, generalized geometric models of loess ridges at varying heights were created, and a three-dimensional nonlinear numerical model was established using FLAC3D. Seismic ground motion time histories at different frequencies and actual earthquake ground motion records were input into the model to analyze the peak acceleration amplification effects experienced by the surface of loess ridges when subjected to SV waves. The study's outcomes reveal that seismic amplification on the slopes of loess ridges is characterized by non-linearity with respect to slope height. Instead, it exhibits rhythmic variations, with the rate of change in these rhythms increasing in correspondence with the frequency of seismic motion and the height of the slope. Under low-intensity seismic motion, a linear increase in acceleration amplification is observed at the ridge's crest concerning the height of the loess ridge. However, under high-intensity seismic motion, the relationship between amplification and slope height becomes less significant. Typically, the peak acceleration at the ridge's crest is reported to be 1.5 to 2.5 times that observed at the slope's base. The amplification effect at the ridge's crest is more pronounced in the low-frequency and high-frequency segments when compared to the mid-frequency range. Conversely, significant amplification is observed in the high-frequency range in the lower sections of the slope near the base. It is further noted that the amplification effect at the ridge's crest displays distinct behavior at different frequencies, characterized by narrow frequency bands of maximum amplification, with peak amplification factors exceeding 10 in some cases. These research findings have practical significance and provide valuable references for engineering construction and seismic risk mitigation planning in loess regions.

Background Plasma S100A1 protein is a novel inflammatory biomarker associated with acute myocardial infarction and neurodegenerative disease’s pathophysiological mechanisms. This study aimed to determine the levels of this protein in patients with acute ischemic stroke early in the disease progression and to investigate its role in the pathogenesis of acute ischemic stroke. Methods A total of 192 participants from hospital stroke centers were collected for the study. Clinically pertinent data were recorded. The volume of the cerebral infarction was calculated according to the Pullicino formula. Multivariate logistic regression analysis was used to select independent influences. ROC curve was used to analyze the diagnostic value of AIS and TIA. The correlation between S100A1, NF-κB p65, and IL-6 levels and cerebral infarction volume was detected by Pearson correlation analysis. Results There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the AIS,TIA, and PE groups (S100A1, [230.96 ± 39.37] vs [185.85 ± 43.24] vs [181.47 ± 27.39], P < 0.001; NF-κB p65, [3.99 ± 0.65] vs [3.58 ± 0.74] vs [3.51 ± 0.99], P = 0.001; IL-6, [13.32 ± 1.57] vs [11.61 ± 1.67] vs [11.42 ± 2.34], P < 0.001). Multivariate logistic regression analysis showed that S100A1 might be an independent predictive factor for the diagnosis of disease (P < 0.001). The AUC of S100A1 for diagnosis of AIS was 0.818 (P < 0.001, 95% CI [0.749–0.887], cut off 181.03, Jmax 0.578, Se 95.0%, Sp 62.7%). The AUC of S100A1 for diagnosis of TIA was 0.720 (P = 0.001, 95% CI [0.592–0.848], cut off 150.14, Jmax 0.442, Se 50.0%, Sp 94.2%). There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the SCI,MCI, and LCI groups (S100A1, [223.98 ± 40.21] vs [225.42 ± 30.92] vs [254.25 ± 37.07], P = 0.001; NF-κB p65, [3.88 ± 0.66] vs [3.85 ± 0.64] vs [4.41 ± 0.45], P < 0.001; IL-6, [13.27 ± 1.65] vs [12.77 ± 1.31] vs [14.00 ± 1.40], P = 0.007). Plasma S100A1, NF-κB p65, and IL-6 were significantly different from cerebral infarction volume (S100A1, r = 0.259, P = 0.002; NF-κB p65, r = 0.316, P < 0.001; IL-6, r = 0.177, P = 0.036). There was a positive correlation between plasma S100A1 and IL-6 with statistical significance (R = 0.353, P < 0.001). There was no significant positive correlation between plasma S100A1 and NF-κB p65 (R < 0.3), but there was statistical significance (R = 0.290, P < 0.001). There was a positive correlation between IL-6 and NF-κB p65 with statistical significance (R = 0.313, P < 0.001). Conclusion S100A1 might have a better diagnostic efficacy for AIS and TIA. S100A1 was associated with infarct volume in AIS, and its level reflected the severity of acute cerebral infarction to a certain extent. There was a correlation between S100A1 and IL-6 and NF-κB p65, and it was reasonable to speculate that this protein might mediate the inflammatory response through the NF-κB pathway during the pathophysiology of AIS.

Abstract With the rapid aging of the population, coronary artery disease (CAD) has become one of the most fatal chronic diseases. However, the genetic mechanism of CAD is still unclear. The purpose of this study is to construct the lncRNA-miRNA-mRNA regulatory network for CAD diseases and systematically identify differentially expressed genes in patients with coronary heart disease. In this study, two lncRNA datasets (GSE69587 and GSE113079) and a microRNA dataset (GSE105449) which contained 393 and 38 CAD samples were selected. In addition, two mRNA datasets which named GSE113079 (98 CAD samples) and GSE9820 (8 CAD samples) were selected to search the differentially expressed genes (DEGs). By comparing the expression data between CAD and control samples, a total of 1111 lncRNAs, 2595 mRNAs and 22 miRNAs were identified. Based on the DEGs, a lncRNA-miRNA-mRNA ceRNA network was constructed to explore the hub nodes in CAD. In the ceRNA network, the lncRNAs KCNQ1OT1 and H19 showed high connectivity with the nine miRNAs. GO and KEGG results showed that genes in ceRNA networks were mainly involved in nitrogen compound metabolic process, PI3K-Akt signaling pathway and retrograde endocannabinoid signaling. These findings will improve the understanding of the occurrence and development mechanism of CAD.

Abstract The effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = − 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = − 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = − 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.

Abstract Convergence insufficiency (CI) is the most common binocular vision problem, associated with blurred/double vision, headaches, and sore eyes that are exacerbated when doing prolonged near work, such as reading. The Convergence Insufficiency Neuro-mechanism Adult Population Study (NCT03593031) investigates the mechanistic neural differences between 50 binocularly normal controls (BNC) and 50 symptomatic CI participants by examining the fast and slow fusional disparity vergence systems. The fast fusional system is preprogrammed and is assessed with convergence peak velocity. The slow fusional system optimizes vergence effort and is assessed by measuring the phoria adaptation magnitude and rate. For the fast fusional system, significant differences are observed between the BNC and CI groups for convergence peak velocity, final position amplitude, and functional imaging activity within the secondary visual cortex, right cuneus, and oculomotor vermis. For the slow fusional system, the phoria adaptation magnitude and rate, and the medial cuneus functional activity, are significantly different between the groups. Significant correlations are observed between vergence peak velocity and right cuneus functional activity (p = 0.002) and the rate of phoria adaptation and medial cuneus functional activity (p = 0.02). These results map the brain-behavior of vergence. Future therapeutic interventions may consider implementing procedures that increase cuneus activity for this debilitating disorder.

It has been revealed that 2′3′-cyclic-GMP-AMP (cGAMP), a second messenger that activates the antiviral stimulator of IFN genes (STING), elicits an antitumoral immune response. Since cGAMP cannot cross the cell membrane, it is not clear how intracellular STING has been activated by extracellular cGAMP until SLC19A1 was identified as an importer to transport extracellular cGAMP into the cytosol. However, SLC19A1-deficient cells also sense extracellular cGAMP, suggesting the presence of mechanisms other than the facilitating transporters for STING sensing extracellular cGAMP. Here, using immunoprecipitation, immunofluorescence, and flow cytometry, we identified an alternatively spliced STING isoform, plasmatic membrane STING (pmSTING), that localized in the plasma membrane with its C-terminus outside the cell, due to a lack of 1 transmembrane domain in its N-terminus compared with canonical STING. Further studies showed that extracellular cGAMP not only promoted the dimerization of pmSTING and interaction of pmSTING with TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3), but also enhanced the phosphorylation of TBK1 and IRF3 and the production of IFN in pmSTING-transfected cells. Additionally, we also identified similar pmSTING isoforms in other species including human. This study suggests a conserved role for pmSTING in sensing extracellular cGAMP and provides insight into the role of cGAMP as an immunotransmitter.

Functional connectivity has been demonstrated to be varying over time during sensory and cognitive processes. Quantitative examinations of such variations can significantly advance our understanding on large-scale functional organizations and their topological dynamics that support normal brain functional connectome and can be altered in individuals with brain disorders. However, toolboxes that integrate the complete functions for analyzing task-related brain functional connectivity, functional network topological properties, and their dynamics, are still lacking. The current study has developed a MATLAB toolbox, the Graph Theoretical Analysis of Task-Related Functional Dynamics (GAT-FD), which consists of four modules for sliding-window analyses, temporal mask generation, estimations of network properties and dynamics, and result display, respectively. All the involved functions have been tested and validated using functional magnetic resonance imaging data collected from human subjects when performing a block-designed task. The results demonstrated that the GAT-FD allows for effective and quantitative evaluations of the functional network properties and their dynamics during the task period. As an open-source and user-friendly package, the GAT-FD and its detailed user manual are freely available at https://www.nitrc.org/projects/gat_fd and https://centers.njit.edu/cnnl/gat_fd/.

Shipping emissions have aroused wide concern in the world. In order to promote the implementation of emission regulations, this study develop a ship based sniffing technique to perform remote measurement of the SO2, NOx and CO2 from ships entering and leaving Shanghai port at the open sea. The ship emission prediction model, Smoke diffusion model and source identification model were developed to automatically analyze the emission data and screen the object ship source based on Automatic Identification System (AIS) system. The fueling documents of the detected ship were obtained from maritime sector and the results precision of the sniffer technique was evaluated by comparing the measured Fuel sulfur content (FSC) with actual value deduced from fueling documents. The influences of wind speed and direction, object ship parameters and monitoring distance on the identification of object ship and accuracy of the calculated FSC were thoroughly investigated and the corresponding correction factors under different conditions were deduced. The modified emission factor ratio of CO2 to NOx were proposed in order to improve the accuracy. It is demonstrated that with wind speed higher than 2 m/s and test distance shorter than 400m, the sniffer technique exhibit high efficiency and accuracy for the remote emissions measurement of ship upwind with detection rate higher than 90% and test error of FSC below 15%. To reduce the influence of the wind direction, at least two sniffer systems were required to guarantee that at least one station is in the downwind of the ship lane. Based on the results and discussion, a novel sniffer monitoring system with two buoy based sniffing stations placed close to each side of the ship lane far off shore was proposed to realize the remote monitoring of ship emissions.

Different from vehicle engines, Diesel Particulate Filter (DPF) inactivation is an unavoidable issue for low-speed marine diesel engines fueled with Heavy Fuel Oil (HFO). This paper introduced a sulfur resisting material in Silicon Carbide (SiC)-DPF to improve DPF performance. The results of bench-scale experiments showed that the Balance Point Temperature of the modified DPF module was 300°C and DPF modules had a good filtration performance, with Particulate Matters (PMs) residual being less than 0.6 g per cycle. In pilot-scale tests, PMs emissions of unit power decreased with engine load going up, filtration efficiency of nucleation mode PMs being only 36% under 100% load, while DPF still had a good performance in accumulation mode PMs control, being 94.2% under the same load. DPF modules showed excellent regeneration durability in the 205h endurance test, with a regeneration period of 1.5-2h under 380°C. There was no obvious degeneration in the DPF module structure, with no cracks or breakage. Besides, the DPF module could also control gaseous emissions, total emissions decreased by 10.53% for NO and 57.19% for CO, respectively. The results suggested that introducing sulfur-resisting material in DPF could greatly improve the DPF performance of low-speed marine diesel engines fueled with HFO.

Aims To develop a nomogram for incident chronic kidney disease (CKD) risk evaluation among community residents with high cardiovascular disease (CVD) risk.Methods In this retrospective cohort study, 5730 non-CKD residents with high CVD risk participating the National Basic Public Health Service between January 2015 and December 2020 in Guangzhou were included. Endpoint was incident CKD defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 during the follow-up period. The entire cohorts were randomly (2:1) assigned to a development cohort and a validation cohort. Predictors of incident CKD were selected by multivariable Cox regression and stepwise approach. A nomogram based on these predictors was developed and evaluated with concordance index (C-index) and area under curve (AUC).Results During the median follow-up period of 4.22 years, the incidence of CKD was 19.09% (n=1094) in the entire cohort, 19.03% (727 patients) in the development cohort and 19.21% (367 patients) in the validation cohort. Age, body mass index, eGFR 60–89 mL/min/1.73 m2, diabetes and hypertension were selected as predictors. The nomogram demonstrated a good discriminative power with C-index of 0.778 and 0.785 in the development and validation cohort. The 3-year, 4-year and 5-year AUCs were 0.817, 0.814 and 0.834 in the development cohort, and 0.830, 0.847 and 0.839 in the validation cohort.Conclusion Our nomogram based on five readily available predictors is a reliable tool to identify high-CVD risk patients at risk of incident CKD. This prediction model may help improving the healthcare strategies in primary care.

Abstract Based on the structural characteristics of the anodes of lithium-ion batteries, an improved Hummers’ method is proposed to recycle the anode materials of spent lithium-ion batteries into graphene. In order to effectively separate the active material from the copper foil, water was selected as an ultrasonic solvent in this experiment. In order to further verify whether lithium ions exist in the active material, carbon powder, it was digested by microwave digestion. ICP-AES was then used to analyse the solution. It was found that lithium ions were almost non-existent in the carbon powder. In order to further increase the added value of the active material, graphene oxide was obtained by an improved Hummers’ method using the carbon powder. The graphene material was also reduced by adding vitamin C as a reducing agent through a chemical reduction method using graphene oxide. Meanwhile, the negative graphite, graphite oxide and graphene samples were characterized by XRD, SEM, FTIR and TEM. The conductivity of the negative graphite, graphite oxide and graphene was tested. The results show that graphene prepared by a redox method has a better layered structure, less impurities and oxygen groups in its molecular structure, wider interlayer spacing and smaller resistivity.

Organizations need both employee voice and managerial endorsement to ensure high-quality decision-making and achieve organizational effectiveness. However, a preponderance of voice research focuses on employee voice with little attention paid to voice endorsement. Building on the social persuasion theory of the elaboration likelihood model, we systematically examine the sender and receiver determinants of voice endorsement and how the interplay of those determinants affects voice endorsement. By empirically analyzing 168 paired samples, we find that issue-relevant information, i.e., voicer credibility, has a positive effect on voice endorsement and matters most when leaders have high felt obligation. The results also show that the peripheral cue used in the study, i.e., positive mood, has a positive effect on voice endorsement and matters most when leaders have low felt obligation or low cognitive flexibility. We discuss the contributions of these findings and highlight limitations and directions for future research.

Background The gut microbiome and microbiome-gut-brain (MGB) axis have been receiving increasing attention for their role in the regulation of mental behavior and possible biological basis of psychiatric disorders. With the advance of next-generation sequencing technology, characterization of the gut microbiota in schizophrenia (SZ) patients can provide rich clues for the diagnosis and prevention of SZ. Methods In this study, we compared the differences in the fecal microbiota between 82 SZ patients and 80 demographically matched normal controls (NCs) by 16S rRNA sequencing and analyzed the correlations between altered gut microbiota and symptom severity. Results The alpha diversity showed no significant differences between the NC and SZ groups, but the beta diversity revealed significant community-level separation in microbiome composition between the two groups (pseudo-F =3.337, p < 0.001, uncorrected). At the phylum level, relatively more Actinobacteria and less Firmicutes (p < 0.05, FDR corrected) were found in the SZ group. At the genus level, the relative abundances of Collinsella, Lactobacillus, Succinivibrio, Mogibacterium, Corynebacterium, undefined Ruminococcus and undefined Eubacterium were significantly increased, whereas the abundances of Adlercreutzia, Anaerostipes, Ruminococcus and Faecalibacterium were decreased in the SZ group compared to the NC group (p < 0.05, FDR corrected). We performed PICRUSt analysis and found that several metabolic pathways differed significantly between the two groups, including the Polyketide sugar unit biosynthesis, Valine, Leucine and Isoleucine biosynthesis, Pantothenate and CoA biosynthesis, C5-Branched dibasic acid metabolism, Phenylpropanoid biosynthesis, Ascorbate and aldarate metabolism, Nucleotide metabolism and Propanoate metabolism pathways (p < 0.05, FDR corrected). Among the SZ group, the abundance of Succinivibrio was positively correlated with the total Positive and Negative Syndrome Scale (PANSS) scores (r = 0.24, p < 0.05, uncorrected) as well as the general PANSS scores (r = 0.22, p < 0.05, uncorrected); Corynebacterium was negatively related to the negative scores of PANSS (r = 0.22, p < 0.05, uncorrected). Conclusions Our findings provided evidence of altered gut microbial composition in SZ group. In addition, we found that Succinvibrio and Corynebacterium were associated with the severity of symptoms for the first time, which may provide some new biomarkers for the diagnosis of SZ.

Hepatitis E virus (HEV) is zoonotic and the leading cause of acute viral hepatitis worldwide. Rabbit HEV can infect humans and is prevalent globally. It is reported that laboratory rabbits are also naturally infected with HEV. Therefore, it is important to investigate in a large scale the prevalence of HEV in laboratory rabbits. Serum samples were collected from 649 laboratory rabbits of 13 different commercial vendors in Beijing, China, from 2017 to 2019, and anti-HEV and HEV antigen (Ag) were tested. Fecal samples were collected from 50 laboratory rabbits from one of the vendors for HEV RNA detection. Six laboratory rabbits with natural HEV infection were euthanized and their liver, kidney, bile and urine samples were collected for HEV RNA quantification. Liver tissues were subjected to histopathology analysis. The overall positive rates of anti-HEV antibodies and HEV-Ag are 2.6% (15/588) and 7.9% (51/649), respectively. HEV RNA was detected in 12.0% (6/50) of the rabbits. High viral load of HEV RNA was detected in liver and bile samples. Liver inflammation was observed. HEV is circulating in laboratory rabbit population in China. Strict screening is crucial to ensure experimental accuracy and prevent zoonotic transmission to research personnel.

Background Recent studies showed that circRNAs are involved in the biological process of some human cancers. However, little is known about their functions in colorectal cancer (CRC). Methods Here we first revealed the expression profiles of circRNAs in the CRC tissues and the adjacent non-tumorous tissues using high-throughput sequencing. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs were also explored. The miRNA and mRNA expression profiles were then obtained by analyzing relevant CRC data retrived from the TCGA database. We obtained and analyzed the competing endogenous RNA (ceRNA) network of the top three pairs of the largest up-regulated and down-regulated circRNAs. Results In this study, we obtained 50,410 circRNAs in the CRC tissue and the adjacent non-tumor tissues, of which 33.7% (16,975) were new, and revealed differential changes in circRNA expression during colorectal carcinogenesis. We have identified six potential key circRNAs (circPIEZO1-3, hsa_circ_0067163, hsa_circ_0140188, hsa_circ_0002632, hsa_circ_0001998 and hsa_circ_0023990) associated with CRC, which play important roles in carcinogenesis as ceRNA for regulation of miRNA-mRNA network. In the subsequent KEGG analysis, several CRC-related pathways were found. Conclusions Our findings advance the understanding of the pathogenesis of CRC from the perspective of circRNAs and provide some circRNAs as candidate diagnostic biomarkers or potential therapeutic targets.

The research about unmanned aerial vehicle (UAV) swarm has developed rapidly in recent years, especially the UAV swarm with sensors which is becoming common means of achieving situational awareness. Due to inadequate researches of the UAV swarm with complex control structure currently, we propose a patrolling task planning algorithm for the UAV swarm with double-layer centralized control structure under the uncertain and dynamic environment. The main objective of the UAV swarm is to collect environment information as much as possible. To summarized, the primary contributions of this paper are as follows. We first define the patrolling problem. After that, the patrolling problem is modeled as the Partially Observable Markov Decision Process (POMDP) problem. Building upon this, we put forward a myopic and scalable online task planning algorithm. The algorithm contains online heuristic function, sequential allocation method, and the mechanism of bottom-up information flow and top-down command flow, reducing the computation complexity effectively. Moreover, as the number of control layers increases, this algorithm guarantees the performance without increasing the computation complexity for the swarm leader. Finally, we empirically evaluate our algorithm in the specific scenarios.

Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been shown to be involved in various human malignancies. Whether it plays a role in colorectal cancer (CRC) development remains unclear. Here, we investigated whether and through what mechanism LRG1 functions in human CRC cells. The plasma level of LRG1 was significantly increased in CRC patients, but it was remarkably decreased in patients with resected colorectal cancers. Meanwhile, both mRNA and protein levels of LRG1 were remarkable overexpressed in CRC tissues than normal tissues. The knockdown of LRG1 significantly inhibited cell proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in SW480 and HCT116 cells in vitro. In addition, LRG1 silencing led to the downregulation of the levels of key cell cycle factors, such as cyclin D1, B, and E and anti-apoptotic B-cell lymphoma-2(Bcl-2). However, it up-regulated the expression of pro-apoptotic Bax and cleaved caspase-3. Furthermore, RUNX1 could be induced by LRG1 in a concentration-dependent manner, while the knockdown of RUNX1 blocked the promotion of the proliferation and inhibition of apoptosis induced by LRG1. Collectively, these findings indicate that LRG1 plays a crucial role in the proliferation and apoptosis of CRC by regulating RUNX1 expression. Thus, LRG1 may be a potential detection biomarker as well as a marker for monitoring recurrence and therapeutic target for CRC.

The recent outbreaks of Zika virus (ZIKV) disease have caused worldwide concerns. Guangdong province is one of the commercial centers in China and communicates frequently with the epidemic areas. To date, 65.2% of the ZIKV infection cases in China were imported via port of entry in Guangdong. The continuous surveillance of imported cases is crucial for the prevention and control of potential ZIKV infection outbreak in China. In this study, a strain of ZIKV was isolated from the serum of a 6-year-old child returning from Venezuela. The morphology of the ZIKV was analyzed in vivo and in vitro by electron microscopy, and clusters of virus particles were found in the loose cytoplasmic membrane structures. The genomic sequence of the isolated ZIKV was determined, and the alignment and phylogenetic analysis identified one unique amino acid substitution occurring in the non-structural protein 4B (NS4B), and the isolated virus belonged to the Asian lineage.

Gastrointestinal neuroendocrine neoplasms (GI-NENs) are often located in the deep mucosa or submucosa, and the efficacy of endoscopic biopsy for diagnosis and treatment of GI-NENs is not fully understood.The current study analyzed GI-NENs, especially those diagnosed pathologically and resected endoscopically, and focused on the biopsy and cold biopsy forceps polypectomy (CBP) to analyze their roles in diagnosing and treating GI-NENs.Clinical data of all GI-NENs were reviewed from January 2006 to March 2012. Histopathology was used to diagnose GI-NENs, which were confirmed by immunohistochemistry.67.96% GI-NENs were diagnosed pathologically by endoscopy. Only 26.21% were diagnosed pathologically by biopsies before treatment. The diagnostic rate was significantly higher in polypoid (76.47%) and submucosal lesions (68.75%), than in ulcerative lesions (12.00%). However, biopsies were only taken in 56.31% patients, including 51.52% of polypoid lesions, 35.56% of submucosal lesions and 100.00% of ulcerative lesions. Endoscopic resection removed 61.76% of GI-NENs, including six by CBP, 14 by snare polypectomy with electrocauterization, 28 by endoscopic mucosal resection (EMR) and 15 by endoscopic submucosal dissection (ESD). 51.52% polypoid GI-NENs had infiltrated the submucosa under microscopic examination. CBP had a significantly higher rate of remnant (33.33%) than snare polypectomy with electrocauterization, EMR and ESD (all 0.00%).Biopsies for all polypoid and submucosal lesions will improve pre-operative diagnosis. The high rate of submucosal infiltration of polypoid GI-NENs determined that CBP was inadequate in the treatment of GI-NENs. Diminutive polypoid GI-NENs that disappeared after CBP had a high risk of remnant and should be closely followed up over the long term.

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage.

Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer's disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.

Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

BACKGROUND: Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99-1.51; P = 0.06; I (2) = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97-1.36; P = 0.111; I (2) = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease. CONCLUSIONS: Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41;

BACKGROUND: The prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese. METHODOLOGY/PRINCIPAL FINDINGS: This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions) method. Data were analyzed by R language and multifactor dimensionality reduction (MDR) software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002) and Arg399Gln (P = 0.017), and in allele distributions of Thr241Met (P = 0.005). Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR): 2.47; 95% confidence interval (95% CI): 1.48-4.13; P

Tryptase, the most abundant mast cell (MC) granule protein, plays an important role in atherosclerosis plaque development. To test the hypothesis that tryptase participates directly in atherosclerosis plaque haemorrhage, the gene sequence and siRNA for tryptase were cloned into a lentivirus carrier and atherosclerosis plaque haemorrhage models in ApoE-/- mice were constructed. After a cuffing-cervical artery operation, the mice were randomly divided into 6 groups. Hematoxylin and eosin(HE) staining showed that the cervical artery plaque area was much larger in the tryptase overexpression group compared to the other groups, and there was greater artery stenosis. The artery stenosis from the cuff-side in all groups was more than 90%, except the siRNA group. Tryptase promotes plaque haemorrhage distinctively because 50% of the mice in the tryptase overexpression group had plaque haemorrhage, while only 10% in the siRNA group did. The immunohistochemistry of the cervical artery plaque showed that plasminogen activator inhibitor-1 (PAI-1) expression was the lowest while tissue plasminogen activator (tPA), CD31, CD34 and VEGF was the highest in the tryptase overexpression groups. This observation was completely contrary to what was observed in the siRNA group. Tryptase promoted bEnd.3 cell growth, migration and capillary-like tube formation, which suggests that tryptase can promote microvessel angiogenesis. PAI-1 expression was inhibited, while tPA expression was increased by tryptase in bEnd.3 cells. Our in vivo and in vitro studies suggest that trypase can promote atherosclerotic plaque haemorrhage by promoting angiogenesis and regulating the balance of PAI-1 and tPA. Thus, regulating tryptase expression in MCs may provide a potential target for atherosclerosis treatment.

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.

BACKGROUND: The hematopoietically-expressed homeobox (HHEX) gene is identified as a promising candidate for type 2 diabetes by genome-wide association studies, triggering plenty of subsequent replications; however, the results are conflicting. We therefore conducted a meta-analysis of three widely-evaluated polymorphisms in HHEX gene and diabetes risk. METHODOLOGY/PRINCIPAL FINDINGS: A random-effects model was adopted irrespective of heterogeneity. Data and study quality were assessed in duplicate. There were 49 studies (cases/controls: 57931/74658) for rs1111875, 18 studies (18227/30366) for rs5015480 and 26 studies (25725/30579) for rs7923837, respectively. Overall analyses indicated that rs1111875-C allele (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.13-1.2; P

BACKGROUND: The association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions) method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR) = 0.99; 95% confidence interval (CI): 0.92-1.06; P = 0.692) and dominant (OR = 0.98; 95% CI: 0.89-1.08; P = 0.637) models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis. CONCLUSIONS: Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.

BACKGROUND: Lung cancer is the most common cause of cancer-related deaths worldwide. The aim of this study was to investigate the association of five extensively-studied polymorphisms in PTGS2 (rs689466, rs5275, rs20417) and CYP2E1 (rs2031920, rs6413432) genes with lung cancer risk in a large northeastern Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: This is a hospital-based case-control study involving 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR method. Data were analyzed using Haplo.stats and MDR programs. There were significant differences between patients and controls in allele/genotype distributions of rs5275 (P = 0.002/0.003) and rs6413432 (P = 0.037/0.044), as well as in genotype distributions of rs689466 (P = 0.02). The risk for lung cancer associated with the rs5275-C mutant allele was decreased by 60% (95% CI [confidence interval]: 0.21-0.74; P = 0.004) under the recessive model. Carriers of rs689466-G mutant allele had a 28% (95% CI: 0.57-0.92; P = 0.008) reduced risk of developing lung cancer relative to the AA genotype carriers. In haplotype analysis, haplotype G-C-C-T (in order of rs689466, rs5275, rs2031920 and rs6413432) decreased the odds of lung cancer by 28% (95% CI: 0.51-0.93; P = 0.019) after adjusting for confounding factors, whereas haplotype A-T-T-T had 1.49-fold (95% CI: 1.21-1.79; P = 0.012) increased risk for lung cancer. Using MDR method, the overall best model including rs5275, rs689466 and rs6413432 polymorphisms was identified with a maximal testing accuracy of 66.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.003). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrated a potentially synergistic association of PTGS2 and CYP2E1 polymorphisms with the underlying cause of lung cancer in northeastern Chinese.

Abstract Gas saturation is a critical parameter for the selection and development of coalbed methane, as well as a key indicator reflecting the challenges in coalbed methane development and productivity evaluation of coalbed methane wells. As one of the significant factors influencing gas saturation, gas content plays a vital role in comprehensively investigating coal pore properties to fully comprehend the process and conditions of methane adsorption and desorption. In this study, 3# and 15# coals from Qinshui Basin, China was selected as research subjects. The experimental evaluation encompassed an examination of composition, pore characteristics, permeability characteristics of coal, rock mechanical parameters while discussing the impact of temperature and pressure on coal's adsorption and desorption capacity. The mineral characteristics analysis revealed that vitrinite is the main component with varying percentages and reflectance values in both 3# and 15# coal seams. The gas content and methane concentration in the 15# coal seam are higher than those in the 3# coal seam. The relationship between gas content within a coal seam and burial depth depends on achieving a balance between positive pressure effects caused by overburden stress exertion on gases trapped within pores under high pressures during burial history versus negative temperature effects due to cooling during geological processes over time. Predictions were made regarding deep-coal gas content which holds significant implications for accurately understanding variations in desorption behavior along with optimizing fracturing engineering.

Objectives To appraise the quality of clinical practice guidelines (CPGs) and expert consensus statements on rehabilitation for patients with COVID-19, summarise recommendations of rehabilitation assessments and interventions and evaluate the heterogeneity of the recommendations.Design Systematic review.Data sources PubMed and Embase databases and five online guideline repositories: The National Guideline Clearinghouse, Guidelines International Network, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence and WHO were searched from their inception to August 2024. In addition, we reviewed reference lists of eligible citations and searched the grey literature on the relevant websites.Eligibility criteria for selecting studies We included CPGs and expert consensus statements which provided information about rehabilitation of patients with COVID-19. To be eligible, the CPGs and expert consensus statements were issued in English by a nationally or internationally recognised government authority, medical/academic society or organisation. If there were multiple versions of the guidelines, we included the latest one. The translations, interpretations and abstracts of guidelines were excluded.Data extraction and synthesis All recommendations on rehabilitation assessments and interventions for COVID-19 were extracted and summarised. Two reviewers independently evaluated the methodological quality with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and two other reviewers assessed the reporting quality using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement of included CPGs and expert consensus statements. We used the Measurement Scale of Rate of Agreement to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements.Results A total of 31 CPGs and expert consensus statements were included. 14 guidelines provided recommendations for rehabilitation assessments. At the early, development, critical and recovery stages of COVID-19, the most frequently recommended were exercise therapy (25.8%, 35.5%, 25.8% and 58.1%, respectively). According to AGREE II, 17 included guidelines were assessed as low methodological quality (35%–56%), 10 guidelines were rated as moderate quality (46%– 62%) and four had high quality (69%–79%). Among 31 eligible guidelines, the reporting rate of 22 items in the RIGHT checklist ranged from 10% to 100%. The included guidelines were consistent with the reference guidelines (80%–100%). Only one guideline existed minor (60%–80%) disagreements in respiratory muscle training relative to the reference guideline.Conclusions Rehabilitation assessments and interventions should be implemented consistently throughout the entire process of COVID-19. The recommendations should be tailored to each stage of COVID-19. The methodological and reporting qualities of several guidelines remain suboptimal. Therefore, developers should adhere strictly to the AGREE II standard and RIGHT checklist to formulate and publish CPGs and expert consensus statements with high quality.PROSPERO registration number CRD42020190761.