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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]

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]

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]

The control of antibiotic resistance genes (ARGs) and removal of nitrogen are the main challenges in antibiotic wastewater treatment. This study adopted the multielectrode microbial fuel cell (MFC) to promote autotrophic denitrification and adopted agricultural waste as a slow-release carbon source to enhance heterotrophic denitrification while running in a siphoning mode. The associated metabolic process and mechanism were explored. The results showed that the electrochemical catalysis and siphoning aeration significantly improved the removal of COD and antibiotics. The number of ARGs and MGEs decreased significantly when both the electrochemical process and the siphoning mode were used. The removal of NH 4 +-N was limited under open-circuit conditions, and the removal was lower than 35.4% in all the reactors. Under electrochemical conditions, the addition of slow-release carbon sources promoted heterotrophic denitrification, and the removal of TN increased by 42.9%. The microbial mechanism of nitrogen removal and ARG control under the electrochemical process were revealed by metagenomic analysis. Compared with the control group, there were a large number of functional genes related to iron REDOX (oorB , oorD , moxR , moxA , mnxG , and mcoA) in the system, which promoted the efficiency of nitrogen removal through coupling with genes related to the nitrogen metabolic pathway. The results can provide a reference for ARGs control and nitrogen removal in the treatment of antibiotic wastewater containing high nitrogen concentrations. • Electrochemical catalysis and siphon aeration significantly improved COD and antibiotics removal. • Antibiotic resistance genes and mobile gene elements can be effectively controlled. • Electrochemical process and slow release carbon source promoted TN removal. • More than 19 major metabolic pathways were detected in the electrochemical system. • MGEs are closely related to horizontal gene transfer in ARGs. [ABSTRACT FROM AUTHOR]

T cells are strongly regulated by oxidizing environments and amino acid restriction. How T cells reprogram metabolism to adapt to these extracellular stress situations is not well understood. Here, we show that oxidizing environments and amino acid starvation induce ATF4 in CD4+ T cells. We also demonstrate that Atf4 -deficient CD4+ T cells have defects in redox homeostasis, proliferation, differentiation, and cytokine production. We further reveal that ATF4 regulates a coordinated gene network that drives amino acid intake, mTORC1 activation, protein translation, and an anabolic program for de novo synthesis of amino acids and glutathione. ATF4 also promotes catabolic glycolysis and glutaminolysis and oxidative phosphorylation and thereby provides precursors and energy for anabolic pathways. ATF4-deficient mice mount reduced Th1 but elevated Th17 immune responses and develop more severe experimental allergic encephalomyelitis (EAE). Our study demonstrates that ATF4 is critical for CD4+ T cell-mediated immune responses through driving metabolic adaptation. • Oxidizing environments and amino acid starvation induce ATF4 in CD4+ T cells • ATF4 increases mTORC1 activation plus intake and de novo synthesis of amino acids • ATF4 enhances glycolysis, glutaminolysis, and oxidative phosphorylation • ATF4 deficiency leads to decreases in Th1 but increases in Th17 immune responses. Oxidizing environments and availability of extracellular amino acids are major mechanisms that regulate T cell proliferation and function. Yang et al. demonstrate that ATF4 drives metabolic reprogramming, which allows CD4+ T cells to adapt to these stresses. [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]

Background: Relatively poor survival and differentiation performance of umbilical cord mesenchymal stem cells (ucMSCs) limits its application of transplantation. The purpose of this study was to investigate the combined effect of ucMSCs and tetramethylpyrazine (TMP) on the histological therapy of ischemia stroke.Methods: Using a middle cerebral artery occlusion (MCAO) model, we sought to determine the therapeutic effects of ucMSCs combined with TMP on ischemic stroke in rats. 1 × 106 ucMSCs was intracerebral transplanted after 24 hours and TMP (50 mg/kg) was injected intraperitoneally every day. After 7 days, the brain tissues were subjected to infarct weight measurement and preparation for 2,3,5-triphenyltetrazolium chloride (TTC) staining, HE staining, and immunohistochemical analysis.Results: The results showed that TMP combined with ucMSCs treatment significantly decreased the neurological deficit score, as well as the cerebral infarct ratio (from 16.33±3.35 to 7.67±1.19%) compared to TMP or ucMSCs treated alone. Moreover, TMP+ucMSCs treatment improved the morphological architecture of the infarct zone, dramatically up-regulated the expression of α-tubulin and nestin, and down-regulated GFAP and IL-1 expression.Conclusions: These data suggest that ucMSCs combined with TMP are able to exert therapeutic effects following ischemic injury by improving neurogenesis, inhibiting inflammation, and ameliorating histological damage. This may therefore be a promising future treatment for ischemic stroke. [ABSTRACT FROM AUTHOR]

• 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]

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]

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]