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Alveolar epithelial cell (AEC) senescence‐induced changes of lung mesenchymal cells are key to starting the progress of pulmonary fibrosis. Follistatin‐like 1 (FSTL1) plays a central regulatory role in the complex process of senescence and pulmonary fibrosis by enhancing transforming growth factor‐β1 (TGF‐β1) signal pathway activity. Activation of Smad4 and Ras relies on SUMO‐specific peptidase 1 (SENP1)‐mediated deSUMOylation during TGF‐β signaling pathway activation. We hypothesized that SENP1‐mediated deSUMOylation may be a potential therapeutic target by modulating FSTL1‐regulated cellular senescence in pulmonary fibrosis. In verifying this hypothesis, we found that FSTL1 expression was upregulated in the lung tissues of patients with idiopathic pulmonary fibrosis and that SENP1 was overexpressed in senescent AECs. TGF‐β1‐induced FSTL1 not only promoted AEC senescence but also upregulated SENP1 expression. Interfering with SENP1 expression inhibited FSTL1‐dependent promotion of AEC senescence and improved pulmonary fibrosis in mouse lungs. FSTL1 enhancement of TGF‐β1 signaling pathway activation was dependent on SENP1 in senescent AEC. Our work identifies a novel mechanism by which FSTL1 is involved in AEC senescence. Inhibition of SENP1 in epithelial cells alleviated pulmonary fibrosis by blocking FSTL1‐enhanced TGF signaling. [ABSTRACT FROM AUTHOR]

To improve the market competitiveness of agricultural e-retailers, we offer an interactive bundle pricing strategy (IBPS). Compared to existing fixed bundling strategies, IBPS takes into account the variability of customer needs and provides consumers with more and more flexible choice opportunities. As more and more consumers tend to buy more environmentally friendly and healthy organic produce, a hybrid bundle pricing model for organic and inorganic produce is developed with the goal of maximizing retailers' profit and optimizing consumers' surplus, taking into account consumers' organic preferences. Meanwhile, we introduce a free shipping strategy to further stimulate consumption. Then, we propose a heuristic algorithm to solve it and derive the optimal price for various bundled packages. Through numerical analysis, we draw some conclusions and propose corresponding management insights: (1) Compared with traditional online retailing methods, IBPS can effectively stimulate consumption and increase retailers' profits; (2) as the free shipping threshold increases, total profits show a trend of first increasing and then decreasing, indicating that an appropriate free shipping threshold can optimize retailers' profits; (3) as consumers' green preferences increase, the sales of organic products increase while the total profit rises, so it is suggested that retailers increase consumer green preference through appropriate advertising; (4) the higher the consumption level, the higher the total value of consumers' word purchases, so retailers can appropriately increase the free shipping threshold at high consumption levels. [ABSTRACT FROM AUTHOR]

Aims and objectives: To investigate the feasibility of using peripheral perfusion index (PPI) to monitor acute limb ischaemia (ALI) in newborns after catheterisations. Background: ALI is common complication of neonatal peripheral artery cannulation. It is important to address as soon as the early signs of ALI. PPI could aid in noninvasive evaluation of distal extremity perfusion in an effort to notify risk of potential ischaemic injury from catheterisations. Design: A nested case–control study. Methods: Clinical information of newborns who had been admitted to the Neonatal Intensive Care Unit of Jiangxi Provincial Children's Hospital and had received peripheral artery cannulation from January 2018 to January 2020 was prospectively collected. Transcutaneous blood oxygen saturation (TcSO2), PPI and delta‐PPI (ΔPPI1; the difference in PPI values of the two arms. ΔPPI2; difference in the PPI values before and after cannulation) were recorded. We used STROBE checklist as an EQUATOR in this study. Results: A total of 25 newborns with ALI were included in the study. These were then paired with 100 newborns without ALI. The PPI and TcSO2 of the cannulated limb were significantly lower in the ALI group than in the non‐ALI (NALI) group (p <.05). The area under the receiver‐operating characteristic curve was significant for ΔPPI1. The ΔPPI1 had a sensitivity and specificity of 92% and 87%, respectively, for diagnosing ALI. ΔPPI1 greater than 0.315 suggested that the infant was at risk of ALI. Conclusions: Monitoring the change in the PPI in newborns after catheterisations helped in the early assessment of ALI. Relevance to clinical practice: Drops in the PPI and TcSO2 of the cannulated limbs might, to some extent, reflect the possibility of ALI in newborns. ΔPPI1 (the difference in PPI values of the two arms) proved to be a simple, objective parameter to predict the presence of ALI. [ABSTRACT FROM AUTHOR]

We perform Bayesian model selection with parameter estimation to identify potentially lensed gravitational-wave images from the second observing run (O2) of Advanced LIGO and Advanced Virgo. Specifically, we compute the Bayesian evidence for a pair of events being lensed or not lensed (unlensed) using nested sampling. We consider in the model selection the discrete coalescence phase shifts that can be induced if the gravitational-wave signal intersects with the lens caustics. We find that the pair of events, GW170104 and GW170814 with a π/2 coalescence phase shift, has a significant Bayes factor () favoring the lensing hypothesis. However, after taking into account the long time delay of approximately 7 months between events, the timing Bayes factor is significantly small (Bt ∼ 8.7 × 10−2). The prior probability for detecting strongly lensed pairs at O2 sensitivity is exceedingly small for both galaxy and galaxy cluster lensing. Combining the lensing and timing Bayes factors with the prior odds on lensing gives an odds ratio of. With the value of the odds ratio after including model dependence of the timing and prior odds factors, we do not have strong evidence to demonstrate that the aforementioned pair is strongly lensed. [ABSTRACT FROM AUTHOR]

V. cholerae , the causative agent of cholera epidemic, and V. fluvialis , the emerging foodborne pathogen, share highly homologous T6SS consisting of one large cluster and two small orphan or auxiliary clusters, and each of which was generally recognized as one operon. Here, we showed that the genes in each of the small clusters are organized into two transcriptional units. Specifically, the inner tube coding gene hcp/tssD is highly transcribed as one monocistron, while the tip component vgrG/tssI and its downstream effector and immunity genes are in one polycistron with very low transcriptional level. This conclusion is supported by qPCR analysis of mRNA abundance, reporter fusion analysis and transcriptional unit definition with RT-PCR analysis. Taking tssI 2_ a of V. fluvialis as an example, we further demonstrated that quorum sensing (QS) regulator HapR and global regulator IHF activate vgrG/tssI transcription by directly binding to its promoter region. Taken together, current studies deepen our understanding of T6SS system, highlighting its regulatory complexity during functional execution process. • hcp and vgrG in T6SS orphan clusters are in different transcripts in V. cholerae and V. fluvialis. • hcp is highly transcripted as a monocistron while vgrG is lowly expressed as a polycistron. • Quorum sensing regulator HapR and global regulator IHF activate vgrG transcription by directly binding to its promoter. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculous meningitis (TBM) is a severe extra-pulmonary tuberculosis with high fatality. This meta-analysis aimed to assess the impact of linezolid on TBM treatment outcomes., Methods: We searched multiple databases for studies published up to May 18, 2024 comparing the effects of linezolid on TBM. Meta-analysis was conducted using Review Manager 5.4., Results: Our findings indicated that linezolid may reduce treatment failure risk (RR = 0.42 (0.20, 0.89), p = 0.02) and improve temperature recovery (RR = 1.56 (1.21, 2.02), p < 0.001) in TBM patients., Conclusions: The analysis suggests a positive association between linezolid treatment and therapeutic improvements, with no significant adverse reactions reported., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Vibrio fluvialis is a halophilic Gram-negative bacterium regarded as an emerging unusual enteric pathogen of increasing public health concern. Our previous work has identified two type VI secretion systems (T6SSs) in V. fluvialis , VflT6SS1, and VflT6SS2, and the latter is functional in mediating interbacterial competitiveness. However, its antibacterial effectors remain to be clarified. In this work, we focused on a new potential effector/immunity pair TssI2/TsiI2. Bioinformatics analysis revealed that the C-terminal domain of TssI2 belongs to a widespread family of pesticin, and its antibacterial toxicity and corresponding protection by TsiI2 were proved via bacterial killing assays, and their action sites were localized to the periplasm of bacterial cells. The interaction of TssI2 and TsiI2 was demonstrated by the bacterial adenylate cyclase two-hybrid, protein pull-down and isothermal titration calorimetry assays. Site-directed mutagenesis demonstrated that, in addition to Glu-844, Thr-863, and Asp-869, which correspond to three reported residues in pesticin of Yersinia pestis , additional residues including Phe-837, Gly-845, Tyr-851, Gly-867, Gln-963, Trp-975, and Arg-1000 were also proved to be crucial to the bactericidal activity of TssI2. Muramidase/lysozyme-related peptidoglycan (PG) hydrolase activities of TssI2 and its variants were validated with permeabilized Escherichia coli cells and purified PG substrate. Based on sequence homologies at C-terminals in various V. fluvialis isolates, TssI2 was subdivided into five clusters (12-22% identity among them), and the antibacterial activities of representative effectors from other four Clusters were also confirmed through periplasmic over-expression in E. coli host. Two selected cognate immunities were proved to confer protection against the toxicities of their effectors. Additionally, TsiI2, which belongs to Cluster I, exhibited cross-protection to effector from Cluster V. Together, current findings expand our knowledge of the diversity and consistency of evolved VgrG effectors in V. fluvialis and on how VflT6SS2 mediates a competitive advantage to gain a better survival.

Background: This study sought to examine the factors influencing acute kidney injury (AKI) in the perioperative period after lung transplantation (LT)., Methods: We collected and analyzed the clinical data of 25 patients, who were diagnosed with AKI in the perioperative period after LT at Sichuan Provincial People's Hospital from July 1, 2018 to June 30, 2020. Based on the clinical outcomes, the patients were divided into an AKI group and a non-AKI group. Differences between the two groups were compared, including differences in mechanical ventilation (MV) time and intensive care unit (ICU) stay time, the mode of transplantation, the total amount of dehydration in the first week after surgery, use of potential kidney damaging drugs, and whether extracorporeal membrane oxygenation (ECMO) was used., Results: Nineteen patients (76%) were diagnosed with AKI in the perioperative period after LT. There were no statistically significant differences between the two groups in terms of basic information, the mode of transplantation, the total amount of dehydration in the first week after surgery, the daily dose of tacrolimus, whether ganciclovir was used, whether voriconazole was used, whether ECMO was used, and mortality (P>0.05). However, the MV time and ICU stay time of the AKI group was longer than that of the non-AKI group (P=0.006, 0.011, respectively). Analysis within the group shows there were no significant differences in terms of mortality, the MV time, and the ICU stay time between the AKI stage two group and the AKI stage three group (all P>0.05). A multi-factor analysis was conducted in which AKI was the dependent variable, whether an amount of dehydration greater than 2,000 mL, a body mass index (BMI) greater than 18, and the use of ganciclovir and voriconazole had been examined as an independent variable; however, none of these were found to be risk factors associated with AKI., Conclusions: The incidence of AKI in the perioperative period after LT is high. AKI in the perioperative period after LT prolonged patients' MV time and ICU stay time. In the perioperative management of LT, it is necessary to consider kidney protection to reduce the risk of AKI.

Objective: To analyze the esophageal dynamics in patients with gastroesophageal reflux disease (GERD) and with refractory cough while undergoing esophageal high-resolution manometry (HRM)., Methods: A total of 32 patients with GERD and with refractory cough and 48 patients with GERD admitted to our hospital from February 2019 to July 2020 were assigned to the combined group and the GERD group, respectively, and 40 healthy volunteers were assigned to the healthy group. All the patients underwent HRM. The lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) parameters, the types of peristalsis of the esophageal body, the esophageal body motility, the i relaxation of LES and UES incidence rates, and the esophageal body motility disorders were compared among the three groups., Results: The combined group and the GERD group had lower esophageal sphincter pressure (LESP) levels and lower 4-s integrated relaxation pressure (4 s IRP) levels, shorter lower esophageal sphincter lengths (LESL), and higher frequencies and longer durations of transient lower esophageal sphincter relaxation (TLESR) compared with the healthy group ( P < 0.05). The upper esophageal sphincter lengths (UESL) in the GERD group were longer than they were in the healthy group ( P < 0.05). Compared with the healthy group and the GERD group, the combined group had longer distal latencies (DL), break distances, and peristaltic breaks (PB), longer large and small peristaltic breaks, a greater number of ineffective swallows, lower upper esophageal sphincter pressure (UESP) levels, distal contraction integrals (DCI), contractile front velocities (CFV), and a higher incidence rate of esophageal body motility disorders ( P < 0.05)., Conclusion: Patients with GERD and with refractory cough often also have esophageal body motility disorders, longer PB, elevated UESP levels, and lower DCI. HRM can be used to objectively evaluate the esophageal dynamics and to differentiate among diseases., Competing Interests: None., (AJTR Copyright © 2021.)

Vibrio fluvialis , an emerging foodborne pathogen of increasing public health concern, contains two distinct gene clusters encoding type VI secretion system (T6SS), the most newly discovered secretion pathway in Gram-negative bacteria. Previously we have shown that one of the two T6SS clusters, namely VflT6SS2, is active and associates with anti-bacterial activity. However, how its activity is regulated is not completely understood. Here, we report that the global regulator integration host factor (IHF) positively modulates the expression and thus the function of VflT6SS2 through co-regulating its major cluster and tssD 2 -tssI 2 (also known as hcp-vgrG ) orphan clusters. Specifically, reporter gene activity assay showed that IHF transactivates the major and orphan clusters of VflT6SS2, while deletion of either ihfA or ihfB , the genes encoding the IHF subunits, decreased their promoter activities and mRNA levels of tssB 2, vasH , and tssM 2 for the selected major cluster genes and tssD 2 and tssI 2 for the selected orphan cluster genes. Subsequently, the direct bindings of IHF to the promoter regions of the major and orphan clusters were confirmed by electrophoretic mobility shift assay (EMSA). Site-directed mutagenesis combined with reporter gene activity assay or EMSA pinpointed the exact binding sites of IHF in the major and orphan cluster promoters, with two sites in the major cluster promoter, consisting with its two observed shifted bands in EMSA. Functional studies showed that the expression and secretion of hemolysin-coregulated protein (Hcp) and the VflT6SS2-mediated antibacterial virulence were severely abrogated in the deletion mutants of Δ ihfA and Δ ihfB , but restored when their trans-complemented plasmids were introduced, suggesting that IHF mostly contributes to environmental survival of V . fluvialis by directly binding and modulating the transactivity and function of VflT6SS2.

To identify the prevalence and characteristics of community-acquired Clostridium difficile infection (CA-CDI) in southwest China, we conducted a cross-sectional study. 978 diarrhea patients were enrolled and stool specimens' DNA was screened for virulence genes. Bacterial culture was performed and isolates were characterized by PCR ribotyping and multilocus sequence typing. Toxin genes tcdA and/or tcdB were found in 138/978 (14.11%) cases for fecal samples. A total of 55 C. difficile strains were isolated (5.62%). The positive rate of toxin genes and isolation results had no statistical significance between children and adults groups. However, some clinical features, such as fecal property, diarrhea times before hospital treatment shown difference between two groups. The watery stool was more likely found in children, while the blood stool for adults; most of children cases diarrhea ≤3 times before hospital treatment, and adults diarrhea >3 times. Independent risk factor associated with CA-CDI was patients with fever. ST35/RT046 (18.18%), ST54/RT012 (14.55%), ST3/RT001 (14.55%) and ST3/RT009 (12.73%) were the most distributed genotype profiles. ST35/RT046, ST3/RT001 and ST3/RT009 were the commonly found in children patients but ST54/RT012 for adults. The prevalence of CA-CDI in Yunnan province was relatively high, and isolates displayed heterogeneity between children and adults groups.

Toll-like receptor 4 (TLR4) is involved in the regulation of host responses to Acinetobacter baumannii ( A. baumannii ). The aim of the present study was to examine the function of TLR4 in lung inflammation in immune-suppressed rats with A. baumannii infection. A total of 72 Sprague-Dawley male rats were randomly divided into the control, A. baumannii infection and immune-suppressed infection groups. The immune-suppressed infection group was treated with 100 mg/kg hydrocortisone by subcutaneous injection every other day for 2 weeks prior to A. baumannii infection. Lung tissue was obtained on the 3rd and 7th day after tracheal inoculation with A. baumannii . The expression of TLR4 in bronchial and alveolar epithelial cells, and alveolar macrophage was examined using immunohistochemistry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid were detected using ELISA. The results showed that in the control group, the expression of TLR4 was upregulated in the bronchial and alveolar epithelial, and alveolar macrophages, and the levels of IL-6 and TNF-α were increased in the early phase of A. baumannii infection. On the 7th day, no significant difference in the levels of IL-6 and TNF-α was observed between the A. baumannii infection and control groups. Conversely, the expression of TLR4 was downregulated in the immune-suppressed group, and the levels of IL-6 and TNF-α were reduced on the 3rd day after infection. In the subsequent observation period, the expression of TLR4 was upregulated and the levels of IL-6 and TNF-α were increased. In conclusion, the results show a critical role of TLR4 in mediating effective immune response in the lung of rat with A. baumannii infection.

Candia tropicalis is an increasingly important human pathogen, causing nosocomial fungemia among patients with neutropenia or malignancy. However, limited research has been published concerning its pathogenicity. Based on the phenotypes of C. tropicalis in our previous study, we selected nine representative strains with different activities of virulence factors (adhesion, biofilm formation, secreted aspartic proteinases, and hemolysins), and one reference strain, ATCC750. The present study aimed to investigate the filamentation ability, the expression of virulence genes (ALST1-3, LIP1, LIP4, and SAPT1-4) and the cell damage of C. tropicalis strains with diverse virulences. C. tropicalis exhibited strain-dependent filamentation ability, which was positively correlated with biofilm formation. Reverse transcriptase PCR analysis showed that the ALST3 and SAPT3 genes had the highest expression in their corresponding genes for most C. tropicalis. The expressions of virulence genes, except ALST3 on polystyrene, were upregulated compared with growth in the planktonic and on human urinary bladder epithelial cell line (TCC-SUP) surface. Clustering analysis of virulence genes showed that isolates had a high biofilm forming ability on polystyrene formed a group. Lactate dehydrogenase assays showed that the cell damage induced by C. tropicalis markedly increased with longer infection time (24 and 48 h). Strain FXCT01, isolated from blood, caused the most serious cell damage; while ZRCT52, which had no filamentation ability, caused the least cell damage. Correlation analysis demonstrated significant correlation existed between adhesion on epithelial cells or the expression of ALST2-3 and cell damage. Overall, our results supported the view that adhesion and filamentation may play significant roles in the cell damage caused by C. tropicalis.

The aim of the present study was to investigate the diagnostic accuracy of Fibroscan for liver fibrosis in patients with chronic hepatitis B (CHB) with alanine aminotransferase (ALT) levels <2 times the upper normal limit. A total of 263 consecutive patients with CHB and ALT levels <2 times the upper normal limit were enrolled in the present study. Liver biopsies and liver stiffness measurements (LSM) were conducted. Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of LSM for the development of liver fibrosis in patients with stage S1, S2 and S3 liver fibrosis. Bivariate Spearman rank correlation analysis was performed in order to determine the association between liver stiffness value, which was measured by Fibroscan, and liver fibrosis stage, which was measured by liver biopsy. The liver stiffness value was found to be positively correlated with the liver fibrosis stage (r=0.522, P<0.001) and necroinflammatory activity (r=0.461, P<0.001), which was measured by liver biopsy. The optimal cut-off value in the patients with stage S1, S2 and S3 liver fibrosis was 5.5, 8.0 and 10.95 kPa, respectively. The area under the ROC curve for the prediction of the development of liver fibrosis in these patients was 0.696, 0.911 and 0.923, respectively. The threshold of the optimal cut-off value exhibited a high sensitivity and specificity. The results of the present study suggested that Fibroscan may improve the sensitivity of the diagnosis of liver fibrosis in patients with CHB and ALT levels <2 times the upper normal limit, and that this sensitivity may increase with the progression of liver fibrosis.