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The purpose of this meta-analysis was to evaluate the diagnostic performance of shear wave elastography (SWE) for the staging of renal fibrosis in patients with chronic kidney disease (CKD). Classification of CKD into mild, moderate and severe fibrosis was based on renal biopsy pathology (glomerulosclerosis, tubulointerstitial injury and vascular sclerosis). The Cochrane Library, Medline, PubMed, Web of Science, EMBASE and CNKI databases were searched from January 1, 2009, to April 20, 2022. Pooled sensitivity, specificity, diagnostic odds ratio and area under the receiver operating characteristic curve (AUROC) were calculated using random effects models. A total of 1394 patients from 14 studies were included in the final analysis. For mild, moderate and severe renal fibrosis, SWE had a sensitivity of 0.79 (95% confidence interval [CI]: 0.67–0.88), 0.73 (95% CI: 0.65–0.80) and 0.87 (95% CI: 0.71–0.95); a specificity of 0.82 (95% CI: 0.75–0.87), 72% (95% CI: 0.67–0.77) and 0.83 (95% CI: 0.80–0.86); an AUROC of 0.87 (95% CI: 0.84–0.90), 0.78 (95% CI: 0.75–0.82) and 0.86 (95% CI: 0.82–0.88); and a diagnostic odds ratio of 17 (95% CI: 7–43), 7 (95% CI: 4–12) and 34 (95% CI: 13–88), respectively. Meta-regressions revealed that the publication date, system used and number of valid measurements of SWE were the main causes of heterogeneity. SWE is a good technique for diagnosing mild and severe renal fibrosis, as well as a fair technique for diagnosing moderate fibrosis. [ABSTRACT FROM AUTHOR]

Background: The present study was conducted to determine the inflammatory response in the lungs of children with Mycoplasma pneumoniae pneumonia (MPP). Methods: This study retrospectively analyzed cytokine levels, cytological findings, and M. pneumoniae (MP)‐DNA level in the bronchoalveolar lavage fluid (BALF) of 96 children with MPP. The study utilized Spearman's correlation method to evaluate the contribution of BALF and blood parameters in MPP children. Results: (1) A total of 96 MPP children were classified into the Low MP‐DNA MPP group (BALF MP‐DNA ≤ 105 copies/mL) and the High MP‐DNA MPP group (BALF MP‐DNA > 105copies/mL); the Non‐fever MPP group (no fever during the entire course of pneumonia) and the Fever MPP group; the Defervescence MPP group (fever had subsided at the time of bronchoscopy) and the Fervescence MPP group; and the Mild MPP group and the Severe MPP group. (2) The High MP‐DNA MPP, Fever MPP, Fervescence MPP, and Severe MPP groups had higher levels of interleukin (IL)‐6, IL‐10, and tumor necrosis factor‐α (TNF‐α) in their BALF (all p <.05). (3) The proportions of neutrophils and macrophages in the BALF of the High MP‐DNA MPP and Fever MPP groups increased and decreased, respectively (all p <.05). (4) In the BALF of MPP children, MP‐DNA, IL‐6, IL‐10, TNF‐α, and interferon gamma (IFN‐γ) levels positively correlated with neutrophil proportion while negatively correlated with macrophage proportion (all p <.05). (5) The MP‐DNA, IL‐6, IL‐10, TNF‐α, and IFN‐γ levels in the BALF of MPP children were positively correlated with the levels of C‐reactive protein, procalcitonin, lactic dehydrogenase, fibrinogen, and d‐dimer, while they were negatively correlated with the albumin level (all p <.05). Conclusions: In children with MPP, the pulmonary inflammatory immune response was stronger in the High MP‐DNA MPP, Fever MPP, Fervescence MPP, and Severe MPP groups. The relationship between pulmonary cytokine levels, MP‐DNA load, and serum inflammatory parameters were found to be weak. [ABSTRACT FROM AUTHOR]

Background: Aberrant methylation of EphA7 has been reported in the process of carcinogenesis but not in cervical cancer. Therefore, an integration study was performed to explore the association between EphA7 hypermethylation and cervical cancer and validate the potential value of EphA7 hypermethylation in the diagnosis of cervical cancer.Methods: We performed an integration study to identify and validate the association between EphA7 methylation and cervical cancer. First, data on EphA7 methylation and expression in cervical cancer were extracted and analyzed via bioinformatics tools. Subsequently, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) were constructed to further demonstrate the association between DNA methylation and EphA7 expression. Ultimately, the clinical value of EphA7 methylation in cervical cancer was validated in cervical tissues and Thinprep cytologic test (TCT) samples by methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP), respectively.Results: Pooled analysis showed that EphA7 promoter methylation levels were significantly increased in cervical cancer compared to normal tissues (P < 0.001) and negatively correlated with EphA7 expression. These prediction results were subsequently confirmed in cell lines; moreover, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) demonstrated that DNA methylation participates in the regulation of EphA7 expression directly. Consistent with these findings, the methylation level and the positive rate of EphA7 gradually increased with severity from normal to cancer stages in TCT samples (P < 0.01).Conclusions: EphA7 hypermethylation is present in cervical cancer and is a potential biomarker for the diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

To explore the feasibility and related mechanism of MFC biosensor for wastewater detection under the action of combined heavy metals. Cyclic voltammetry (CV) and scanning electrochemical impedance spectroscopy (EIS) were used to explore the related bioelectrochemical process. The response of the reactor to single/combined heavy metals, low/high heavy metal concentrations, and the differences in ohmic resistance (Rs) and charge transfer resistance (Rct) were investigated using Ni as the core heavy metal and the combined action of Cd, Cu and Zn. The results indicated that there was a linear relationship between the concentration and output voltage of the MFC biosensor under the action of combined heavy metals (R2 = 0.8803–0.973). However, the internal resistance (Rint) of the MFC biosensor under the action of single heavy metal was far less than that of the combined heavy metal group, and the power density (19.849 W m−3) was 4 times that of the combined heavy metal group (3.109–4.589 W m−3). The Rs of the biosensors in the combined heavy metal group were 0.868Ω and 0.860, which were higher than 0.768Ω of the single heavy metal sensor. With the increase of the concentration of heavy metals in the influent, the increase of Rct was more obvious in the combined group, while the Rs in the single group significantly increased (P < 0.05). The results imply that it is possible for MFC biosensors to be used in the detection of actual water polluted by various heavy metals, but the biosensor performance is mainly limited by Rct, which needs to be further improved. [Display omitted] • The feasibility of MFCs for combined heavy metal biosensor was demonstrated. • Combined heavy metals led to worse MFC-based biosensors performance and higher Rint. • The sensors' performance was mainly controlled by Rct. • The activity of biofilm was not affected by the composition of heavy metal. [ABSTRACT FROM AUTHOR]

Background: The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.Methods: First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROCAUC.Results: Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.Conclusion: SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Biosensors play a very important role in pollutant monitoring, but there are still some problems such as stability, repeatability and low detection limits. Therefore, it is necessary to explore ways to increase the performance of biosensors. In this study, biochar-MFC sensors were constructed for heavy metals monitoring in constructed wetlands (CWs), and the correlation, repeatability and anti-interference were studied. At 1.0 M/L concentrations of heavy metals (Ni, Cu, Zn and Cr), CW with biochar as filler (B-CW) had an output voltage of 0.69 V, extending the detection limit of the sensor. B-CW had advantages in anti-interference and reproducibility. The results showed that B-CW had higher abundance of electrogenic bacteria than CW. Shewanella and Proteobacteria , main electricity-producing bacteria, increased 3-fold. The electrochemically active microorganism Shewanellaceae made up 6.2% of the B-CW microbial population, but was not detected in CW. The abundance of key genes AarC increased by 1295.8% in B-CW. More importantly, the abundance of extracellular electron transport chain related genes (MtrA , OmcA) increased significantly (p < 0.01). Biochar can promote oxidative phosphorylation, thus increasing the sensor's output voltage and detection range. This study is expected to provide support for the engineering application of MFC sensor in CWs. [Display omitted] • MFC-sensors can effectively detect heavy metals in constructed wetlands. • Extracellular electron transfer significantly increased in biochar system. • Biochar increased genes associated with oxidative phosphorylation by about 27%. • Biochar significantly enhanced the repeatability and anti-interference of the sensor. [ABSTRACT FROM AUTHOR]

ABBREVIATIONS COVID-19 coronavirus disease 2019 MERS Middle East respiratory syndrome SARS severe acute respiratory syndrome WHO World Health Organization The recent coronavirus disease 2019 (COVID-19) epidemic is spreading all over the world. SARS infection A retrospective comparative study showed a shorter hospital stay after convalescent plasma therapy in SARS patients who deteriorated despite ribavirin and high-dose steroid therapy (74% vs. 19%; p = 0.001). Convalescent plasma treatment reduced mortality in patients with severe pandemic Influenza A (H1N1) 2009 virus infection. Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial. [Extracted from the article]

To explore the application of biosensor in real-time monitoring of composite heavy metal polluted wastewater in view of the low performance of MFC sensor, this study used sodium alginate to immobilize biochar to the anode of MFC biosensor, and conducted a study on the sensor performance and related biological processes. The results showed that under the optimal HRT conditions, the output power of the MFC-sensor (BC-300) was 0.432 W/m3 after biochar modification, which was much higher than the highest power density of CG and BC-0 of 0.117 and 0.088 W/m3. The correlation coefficient was greater than that of the control group at the plating wastewater concentration of 0.1–1.0 M and had a wider detection range, and the time to recover the output voltage was 1/3 of that of the control group. The biochar significantly promoted the sensitivity, interference resistance, recovery and anti-interference performance of the MFC-sensor. The intrinsic mechanism was that the composition and structure of biochar lead to a 1.53 fold increase in the abundance of electrogenic microorganisms and the abundance of functional genes such as cytochrome c (MtrABC, CymA, Cox, etc.) and flavin (riba, Rib B, gdh, ushA, IDH, etc.) increased by about 1.03–3.20 times, which promoted the shift of electrons from intracellular to extracellular receptors and significantly improved the electron transfer and the energy metabolism efficiency. The results of this study can provide a reference for the application of MFCsensor to the detection of complex heavy metal effluents. [Display omitted] • Biochar enhanced the correlation, sensitivity and resilience of the MFC sensor. • Microbiological mechanism of biochar enhanced sensor performance was revealed. • The relationship between energy metabolism and biochar in MFC sensor was elucidated. • Electron transfer efficiency and gene abundance affected the performance of sensor. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium houstonense is a category of rapidly growing mycobacteria that is gram-positive, acid-fast, polycrystalline, and non-spore-forming. There have been few reports of human infection caused by Mycobacterium houstonense worldwide. Case presentation: We present a case of chronic periprosthetic joint infection caused by Mycobacterium houstonense in an elderly female patient. The patient developed signs of infection after undergoing total hip arthroplasty. Despite receiving antibiotic treatment and revision surgery, the signs of infection recurred repeatedly. Multiple bacterial cultures during the treatment period were negative. Later, we identified the pathogenic bacteria Mycobacterium houstonense through mNGS testing, isolated the bacteria from the ultrasonically centrifuged fluid of the prosthesis and obtained drug sensitivity results. Finally, we performed a revision surgery and treated the patient with moxifloxacin and clindamycin. After treatment, the patient did not show signs of infection recurrence during 24 months of follow-up. Conclusion: Through a relevant literature search, we believe that Mycobacterium houstonense may show higher sensitivity to amikacin and quinolone antibiotics. Additionally, clarifying occult infection sources through methods such as gene testing will improve the diagnosis and treatment of periprosthetic joint infection. [ABSTRACT FROM AUTHOR]

P articularly i nteresting n ew c ysteine- h istidine-rich protein (PINCH) is a LIM-domain-only adaptor that plays important roles in cytoskeletal organization and extracellular matrix adhesion, migration, proliferation and survival. Mammalian cells have two functional PINCH proteins, PINCH1 and PINCH2. PINCH not only binds to Nck2 and engages in the signaling of growth factor receptors, but also forms a ternary complex with ILK and parvin (IPP complex). Normally, the IPP complex locates to focal adhesions participating in the signaling of integrins and mediating the interaction of cytoskeleton and extracellular matrix (ECM). Accumulative evidence indicates that abnormalities in PINCH signaling are involved in the pathogenesis of important diseases, such as cancers, renal diseases, cardiomyopathy, and HIV. Therefore, clarifying the functions of PINCH and its interactions with key factors is important for better understanding of signaling events both in health and disease. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) have been identified in and isolated from numerous human tissues. The characteristics of mesenchymal stem cells, including their plasticity, the secretion of cytokines, and their low immunogenicity, contribute to their therapeutic potential. It has recently been reported that MSCs are also involved in tumorigenesis and its prognosis. Here, we present the first report of MSC-like cells isolated from human gastric cancer tissues. In our study, gastric cancer-derived MSC-like cells (hGC-MSCs) were isolated from 13 out of 20 cancer tissue samples. Their characteristics, including their morphology, surface antigens, specific gene expression, and differentiation potential, were similar to those of MSCs derived from human bone marrow (hBM-MSCs) but different from gastric cancer cells. The existence of MSC-like cells in gastric cancer tissues suggests that they may be potential targets for cancer therapy and provides an experimental foundation for investigating their role in the initiation and progression of gastric cancers. [Copyright &y& Elsevier]

• TMP protected ucMSCs against H 2 O 2 induced-oxidative damage at a low concentration. • ucMSC migration was improved by TMP via the SDF-1/CXCR4 axis. • At a high dose, TMP induced the differentiation of ucMSCs into neuron-like cells. • The secretion of cytokines was significantly increased by TMP Umbilical cord mesenchymal stem cells (ucMSCs) may serve as a new source for cell therapy in stroke patients; however, the poor efficiency of viability, migration, and differentiation limit the application of ucMSCs. This study determined the dose-dependent effects of tetramethylpyrazine (TMP) on the characteristics of ucMSCs in vitro. The effect on proliferation was determined with Cell Counting kit-8 assays. Cell migration was analyzed with Transwell assays and western blot analysis. Differentiation of ucMSCs was evaluated according to markers and the expression of relevant proteins and genes. Secretion capacity was detected by ELISA analysis. TMP protected ucMSCs against H 2 O 2 induced-oxidative damage but had no influence on ucMSC activity at a low concentration. Furthermore, ucMSC migration was improved by TMP via the SDF-1/CXCR4 axis. The observed effects were dose dependent. At a high dose, however, TMP induced the differentiation of ucMSCs into neuron-like cells that expressed neuron-specific markers. In addition, the secretion of cytokines was significantly increased by TMP. Therefore, TMP pre-treatment of ucMSCs may be an effective strategy to enhance the efficiency of ucMSC transplantation in stroke therapy. [ABSTRACT FROM AUTHOR]

Liver injury is closely associated with macrophage activation following HBV infection. Our previous study showed that only HBeAg, but not HBsAg and HBcAg, stably enhances inflammatory cytokine production in macrophages. And we also indicated that HBeAg could induce macrophage activation via TLR2 and thus aggravate the progression of liver fibrosis. However, the specific molecular mechanism of HBeAg in macrophage activation is not clear. We screened significantly overexpressed RGS16 from RNASeq results of HBeAg-stimulated macrophages and validated them with cellular assays, GSE83148 microarray dataset, and in clinical samples. Meanwhile, small interference, plasmid, and lentivirus transfection assays were used to establish cell models for knockdown and overexpression of RGS16, and q-PCR, ELISA, Transwell, and CCK-8 assays were used to analyze the role of RGS16 in HBeAg-induced macrophage activation. In addition, the upstream and downstream mechanisms of RGS16 in HBeAg-treated macrophage activation were explored using inhibitors, phostag gels, and RGS16 phosphorylation mutant plasmids. Finally, the effect of RGS16 on hepatic inflammation in murine tissues was evaluated by H&E staining, liver enzyme assay and immunofluorescence. RGS16 was significantly upregulated in HBeAg-induced macrophage activation, and its expression was enhanced with increasing HBeAg content and treatment time. Functional experiments showed that overexpression of RGS16 promoted the production of inflammatory factors TNF-α and IL-6 and boosted macrophage proliferation and migration, while knockdown of RGS16 exhibited the opposite effect. Mechanistically, we discovered that RGS16 is regulated by the TLR2/P38/STAT5 signaling pathway. Meanwhile, RGS16 enhanced ERK phosphorylation via its own Tyr168 phosphorylation to contribute to macrophage activation, thereby accelerating liver injury. Finally, in mice, overexpression of RGS16 markedly strengthened liver inflammation. HBeAg upregulates RGS16 expression through the TLR2-P38-STAT5 axis, and the upregulated expression of RGS16 enhances macrophage activation and accelerates liver injury by promoting ERK phosphorylation. In this process, phosphorylation of Tyr168 is necessary for RGS16 to function. Key messages: RGS16 boosted HBeAg-induced macrophage inflammation, proliferation, and migration. Tyr168 phosphorylation of RGS16 affected by ERK promoted macrophage activation. HBeAg upregulated the expression of RGS16 through TLR2/P38/STAT5 signal pathway. RGS16 promoted liver injury by regulating macrophage functions in mouse model. [ABSTRACT FROM AUTHOR]

Background. Endothelial dysfunction commonly occurs in obese children and adolescents, leading to an increased risk of cardiovascular diseases. Exercise has significant protective effects against endothelial dysfunction through regulating some noncoding RNAs. This study aimed to investigate the relationship of long noncoding RNA MALAT1 and microRNA-320a (miR-320a) with the exercise-induced improvement of endothelial dysfunction in obese children and adolescents. Methods. Sixty obese children and adolescents were included in this study, including 40 cases that received 12-week exercise training and 20 cases that received only diet control. The anthropometric and blood indices before and after exercise were recorded and compared, and the endothelial dysfunction was evaluated by examining the levels of markers, including VCAM-1, ICAM-1, and E-selectin, using an ELISA assay. The expression levels of noncoding RNAs were assessed using real-time quantitative PCR, and their correlation with patients' recorded indices and endothelial dysfunction markers was analyzed. Results. The 12-week exercise training significantly decreased the levels of VCAM-1, ICAM-1, and E-selectin and could inhibit MALAT1 but promote miR-320a expression in obese children and adolescents. The expression of MALAT1 and miR-320a was correlated with the changes in the anthropometric and blood indices of obese children and adolescents, and their correlations with endothelial dysfunction markers were obtained. Conclusion. All the data revealed that exercise has significantly protective effects against endothelial dysfunction and can regulate the expression of the MALAT1/miR-320a axis. MALAT1 and miR-320a were correlated with endothelial dysfunction markers, indicating that the MALAT1/miR-320a axis may be related with the alleviating effects of exercise on endothelial function in obese children and adolescents. [ABSTRACT FROM AUTHOR]

Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is an important bacterium and responsible for both infections acquired in hospital and community because of its multidrug resistance and the virulence. The aim of this research was to investigate clonal lineages, antibiotic resistance profiles, and virulence factors of the hospital isolated carbapenem-resistant strains. Fifty carbapenem-resistant isolates were phenotypically confirmed extended-spectrum beta-lactamases ESBLs producers. MLST analysis revealed 94% sequence type 11. These isolates mainly belonged to three clones according to the PFGE DNA patterns. PFGE patterns have good discrimination than ST profiles. One isolate, K. pneumoniae KPX, undergoing whole-genome sequencing comprised one circular chromosome and four circular plasmids. This isolate harbored a variety of antimicrobial resistance and virulence determinants. The closest relative of K. pneumoniae KPX was another ST11 clinical isolate recovered Sichuan. In addition, KPC-2 (98.0%), SHV-11 (98.0%), TEM-1 (76.0%), CTX-M (76.0%), oqxB1(66%), qnrS (70%), Int1 (42.0%), sul1 (82.0%), sul2 (96.0%), iutA (88%), iucC(10%), and rmpA2 (100%) genes were presented in multiple drug-resistant isolates. The dataset presented in this study provided the genomic and epidemiological analysis of carbapenem-resistant K. pneumoniae in hospital settings. Antimicrobial-resistant profiles suggested the presence of significant selective antibiotic pressure. Appropriate surveillance is essential to the development of effective control strategies in the prevention of nosocomial infection. [ABSTRACT FROM AUTHOR]

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment. [ABSTRACT FROM AUTHOR]

Tartaric acid (TA) is a major non-fermentable plant soluble acid that abundantly occur in grapes and wines, imparting low pH and tart flavour to berries thereby regulating numerous quality attributes of wine, such as flavour, microbial stability, and aging potential. Evaluation of acidity in mature fruits of 21 wine grape (Vitis vinifera) varieties revealed significant variation between 'Beichun' and 'Gewürztraminer', which was correlated with TA content. RNA-seq analysis of fruits from the two cultivars at different developmental stages revealed that a transketolase gene, VvTK2 , was significantly dominantly expressed in the high TA phenotype 'Beichun' variety. Subcellular localization assay showed that VvTK2 protein was located in the chloroplast. Virus-induced VvTK2 gene silencing significantly decreased the expression of 2-keto-L-gulonic acid reductase (Vv2-KGR) as well as L-idonate dehydrogenase (VvL-IdnDH3) and inhibited TA accumulation, while its transient over-expression in grape showed the opposite results. Heterologous VvTK2 over-expression in tomato demonstrated its obvious capacity to induce TA synthesis. Overall, these results highlights a novel role of VvTK2 in modulating TA biosynthesis, which could be an excellent strategy for future genetic improvement of grape flavour. [ABSTRACT FROM AUTHOR]

Human serum albumins (HSAs) are synthesized in the liver and are the most abundant proteins in plasma of healthy human. They play an important role in the pathophysiological processes of the liver and even the whole organism. Previous studies have mainly focused on the regulation of HSAs' expression. However, with the progress of research in recent years, it has been found that the content of circulating albumin cannot fully reflect the biological function of albumin itself. Given the aforementioned fact, the concept of serum 'effective albumin concentration' has been proposed. It refers to the content of albumin that is structurally and functionally intact. Alterations in the molecular structure and function of albumin have been reported in a variety of diseases, including liver disease. Moreover, these changes have been verified to affect the progression of oxidative stress-related diseases. However, the link between albumin structure and function has not been fully elaborated, and the mechanisms by which different forms of albumin affect disease also need to be further investigated. In this context, the present review mainly expounded the biological characteristics and functions of albumin, summarized the different types of post-translational modification of albumin, and discussed their functional changes and possible mechanisms in non-alcoholic fatty liver disease, alcoholic hepatitis, viral hepatitis and different stages of cirrhosis. This will help to improve understanding of the role of albumin in disease development and provide a more comprehensive physiological basis for it in disease treatment. [ABSTRACT FROM AUTHOR]

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell-extracellular matrix adhesion and migration; however, their roles in adipose tissue and metabolism are unclear. Here we find that high-fat diet (HFD) feeding dramatically increases expression of Pinch1/2 proteins in white adipose tissue (WAT) in mice. Furthermore, expression of Pinch1 is largely upregulated in WAT in leptin-deficient ob/ob type 2 diabetic mice and obese humans. While mice with loss of Pinch1 in adipocytes or global Pinch2 do not display any notable phenotypes, deleting Pinch1 in adipocytes and Pinch2 globally significantly decreases body weight and WAT mass, but not brown adipose tissue mass, in HFD-fed, but not normal chow diet-fed, mice. Pinch loss ameliorates HFD-induced glucose intolerance and fatty liver. After HFD challenge, Pinch loss slightly but significantly accelerates energy expenditure. While Pinch loss decreases adipocyte size and alters adipocyte size distribution, it greatly accelerates cell apoptosis primarily in epididymal WAT and to a lesser extent in subcutaneous WAT. In vitro studies demonstrate that Pinch loss accelerates adipocyte apoptosis by activating the Bim/Caspase-8 pathway. In vivo, genetic ablation of Caspase-8 expression in adipocytes essentially abolishes the ameliorating effects of Pinch deficiency on obesity, glucose intolerance, and fatty liver in mice. Thus, we demonstrate a previously unknown function of Pinch in control of adipose mass, glucose, and fat metabolism via modulation of adipocyte apoptosis. We may define a novel target for the prevention and treatment of metabolic diseases, such as obesity and diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The present study was designed and conducted to compare the efficacy between nasal continuous positive airway pressure (NCPAP), nasal intermittent positive-pressure ventilation (NIPPV), and noninvasive high-frequency oscillatory ventilation (NHFOV) as the primary noninvasive ventilation in preterm infants with respiratory distress syndrome (RDS).Material and Methods: This multicenter retrospective cohort study was performed using data from four tertiary neonatal intensive care units (NICUs) in China between 2016 and 2018. 512 preterm infants with RDS who received early non-invasive ventilation (NIV) were analyzed. Propensity score analysis with 1 : 1 matching was performed with the nearest neighbor matching method using calipers of width equal to 0.1 of the standard deviation of the logit of the propensity score. The primary outcome was the need for intubation and invasive mechanical ventilation (IMV) within the first 7 days after birth. Secondary outcomes were days of hospitalization, predischarge mortality, rate of retinopathy of prematurity (ROP) > stage II, rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age, rate of air leaks, rate of intraventricular hemorrhage (IVH) ≥ grade 3, and rate of necrotizing enterocolitis (NEC) ≥ stage II.Results: Propensity score matching identified 126 infants in each cohort (NHFOV vs. NIPPV), 96 infants in each cohort (NHFOV vs. NCPAP), 134 infants in each cohort (NIPPV vs. NCPAP) respectively. The need for IMV was significantly lower in the NHFOV as compared with NCPAP and NIPPV groups respectively (13/126 vs. 27/126, p = 0.016; 9/96 vs. 20/96, p = 0.027), while no difference was observed between NIPPV and NCPAP groups (25/134 vs. 25/134, p = 0.805). However, the number of days of hospitalization in NIPPV was significantly lower than that of the NCPAP group (24.8 ±14.6 days vs. 33.2 ±20.2 days p = 0.002). In subgroup analyses, the need for IMV was significantly lower in the NHFOV group than in the NCPAP and NIPPV group (7 : 79 vs. 15 : 74; 95% CI: 1.00-6.836; p = 0.044 and 11 : 102 vs. 22 : 98; 95% CI: 1.092-5.251; p = 0.026), and there was no difference between NIPPV and NCPAP in the preterm infants at ≤ 32 weeks' gestational age. There were no significant differences among three groups (p > 0.05 respectively) regarding secondary outcomes.Conclusions: In this multicenter retrospective cohort study, NHFOV significantly reduced the need for IMV within the first 7 days as compared to NCPAP and NIPPV in the treatment of preterm infants with RDS without increasing the incidence of adverse events. However, NIPPV was not found to be superior to NCPAP for decreasing the need for IMV in the treatment of preterm infants with RDS. [ABSTRACT FROM AUTHOR]

This paper brings forth a kind of automatic pressurizing device which can resolve the problem of poor hydraulic support setting load directly without modifying the original hydraulic system excessively. On the basis of the control loop that is designed according to working requirements and conditions to realize automatic pressurization of stand column system, it is divided into pressurizing structure and auxiliary structure. Reserved liquid opening and unit design are used to design the automatic pressurizing device from the principle perspective, and it is also made associated with all units reasonably by improving the details. The automatic pressurizing device combines machinery and hydraulic pressure so that all structural units can finish the expected action and coordinate mutually under the effect of emulsion in order to finally realize the overall function of automatic and fast pressurization. On the basis of the simulated analysis of AMESim hydraulic simulation platform on the control loop and lifting support system loop of support stand column, the working performance of automatic pressurizing device and dynamic characteristics of control loop are simulated. The result after comparing and analyzing the simulation curve and site installation test of underground ZY12000/28/63D support finally shows that the device is able to enhance the setting load to above 30 MPa, which is basically the same with simulation result. It demonstrates that the design of automatic pressurizing device conforms to the expected pressurization requirements and the pressurization effect is significant. [ABSTRACT FROM AUTHOR]

Purpose: Mesenchymal stem cell (MSC)-like cells, a subpopulation of tumor microenvironment, have been isolated from several tumor tissues. In our previous study, we identified MSC-like cells in human gastric cancer tissues and found their characteristics to be similar to those of bone marrow MSCs. However, whether there are MSC-like cells in adjacent non-cancerous tissues and any difference between the MSC-like cells derived from tumor and non-cancerous tissues are not clear. The aim of this study is to study and research the differences of two mesenchymal stem-like cells. Methods: We demonstrate that MSC-like cells can be isolated from both human gastric tumor (hGC-MSCs) and adjacent non-cancerous tissues (hGCN-MSCs) of the same patient. We further compared the characteristics between hGC-MSCs and hGCN-MSCs. Results: Our results revealed that hGC-MSCs and hGCN-MSCs possessed similar morphological properties; stem cell-associated gene expression, as well as multipotential differentiation capability. We also found differences in cell surface markers, pluripotency, and proliferation-related gene expression between hGCN-MSCs and hGC-MSCs. Conclusions: Our findings suggest that MSC-like cells are components of the tumor microenvironment and provide proof for the origin of carcinoma-associated fibroblast, therefore may potentially be used as a target for gastric cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the diagnosis value of urinary inflammatory index (UII) and systemic immune-inflammation index (SII) for UTI. Nine inflammatory indexes including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, SII and six UIIs were calculated for Receiver operating characteristic curve analysis to select which one is suitable for the screening of UTIs or distinguishing the types of bacteria. UII3, which calculated from leucocyte esterase (LE), nitrite, white blood cells and bacteria, was preferentially used as an indicator for the diagnosis of UTI when the threshold was set at 0.53. UII2 was more suitable for the distinction between groups when the cutoff is set to 0.94. Appropriate urinary inflammation index calculated by rapid urinalysis of urine dipstick and urine sediment can help us to predict urinary tract infection and bacterial type, and reduce the workload and costs of urine culture. [ABSTRACT FROM AUTHOR]

The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6 , 12 , 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e , 22a-c and 22e-g exhibited strong binding force against Hsp90N with∣ΔTm∣ > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC 50 values below 25 μM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy. [ABSTRACT FROM AUTHOR]