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Tubular epithelial cells (TECs) exposed to hypoxia incite tubulointerstitial inflammation (TII), while the exact mechanism is unclear. In this study, we identified that hypoxia evoked tubule injury as evidenced by tubular hypoxia-inducible factor-1α and kidney injury molecule-1 (KIM-1) expression and that renal small extracellular vesicle (sEV) production was increased with the development of TII after ischemia-reperfusion injury (IRI). Intriguingly, KIM-1-positive tubules were surrounded by macrophages and co-localized with sEVs. In vitro, KIM-1 expression and sEV release were increased in hypoxic TECs and the hypoxia-induced inflammatory response was ameliorated when KIM-1 or Rab27a, a master regulator of sEV secretion, was silenced. Furthermore, KIM-1 was identified to mediate hypoxic TEC-derived sEV (Hypo-sEV) uptake by TECs. Phosphatidylserine (PS), a ligand of KIM-1, was present in Hypo-sEVs as detected by nanoflow cytometry. Correspondingly, the inflammatory response induced by exogenous Hypo-sEVs was attenuated when KIM-1 was knocked down. In vivo, exogenous-applied Hypo-sEVs localized to KIM-1-positive tubules and exacerbated TII in IRI mice. Our study demonstrated that KIM-1 expressed by injured tubules mediated sEV uptake via recognizing PS, which participated in the amplification of tubule inflammation induced by hypoxia, leading to the development of TII in ischemic acute kidney injury.

Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia.Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed.From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients' all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p 0.05). The predicting factor of a CRE bacteremia episode was the causative agent of Enterobacter spp. (adjusted OR of 2.551, CI 1.073-6.066, p 0.05) and ESBL-producing phenotype (adjusted OR 14.268, CI 5.120-39.762, p 0.001).Bloodstream infections caused by CRE are associated with a higher mortality rate in the pediatric population. Attention must be paid to preventing and managing pediatric patients with CRE infections.

With the coming of the “14th Five-Year Plan”, the coordinated control of particulate matter with an aerodynamic diameter no greater than 2.5 μm (PM2.5) and O3 has become a major issue of air pollution prevention and control in China. The stereoscopic monitoring of regional PM2.5 and O3 and their precursors is crucial to achieve coordinated control. However, current monitoring networks are currently inadequate for monitoring the vertical profiles of both PM2.5 and O3 simultaneously and support air quality control. The University of Science and Technology of China (USTC) has established a nationwide ground-based hyperspectral stereoscopic remote sensing network based on multi-axis differential optical absorption spectroscopy (MAX-DOAS) since 2015. This monitoring network provides a significant opportunity for the regional coordinated control of PM2.5 and O3 in China. One-year vertical profiles of aerosol, NO2 and HCHO monitored from four MAX-DOAS stations installed in four megacities (Beijing, Shanghai, Shenzhen, and Chongqing) were used to characterize their vertical distribution differences in four key regions, Jing–Jin–Ji (JJJ), Yangtze River Delta (YRD), Pearl River Delta (PRD), and Sichuan Basin (SB), respectively. The normalized and yearly averaged aerosol vertical profiles below 400 m in JJJ and PRD exhibit a box shape and a Gaussian shape, respectively, and both show exponential shapes in YRD and SB. The NO2 vertical profiles in four regions all exhibit exponential shapes because of vehicle emissions. The shape of the HCHO vertical profile in JJJ and PRD was Gaussian, whereas an exponential shape was shown in YRD and SB. Moreover, a regional transport event occurred at an altitude of 600–1000 m was monitored in the southwest–northeast pathway of the North China Plain (NCP) by five MAX-DOAS stations (Shijiazhuang (SJZ), Wangdu (WD), Nancheng (NC), Chinese Academy of Meteorological Sciences (CAMS), and University of Chinese Academy of Sciences (UCAS)) belonging to the above network. The aerosol optical depths (AOD) in these five stations decreased in the order of SJZ > WD > NC > CAMS > UCAS. The short-distance regional transport of NO2 in the 700–900 m layer was monitored between WD and NC. As an important precursor of secondary aerosol, the peak of NO2 air mass in WD and NC all occurred 1 h earlier than that of aerosol. This was also observed for the short-distance regional transport of HCHO in the 700–900 m layer between NC and CAMS, which potentially affected the O3 concentration in Beijing. Finally, CAMS was selected as a typical site to determine the O3–NOx–volatile organic compounds (VOCs) sensitivities in vertical space. We found the production of O3 changed from predominantly VOCs-limited conditions to mainly mixed VOCs–NOx-limited condition from the 0–100 m layer to the 200–300 m layer. In addition, the downward transport of O3 could contribute to the increase of ground surface O3 concentration. This ground-based hyperspectral stereoscopic remote sensing network provide a promising strategy to support management of PM2.5 and O3 and their precursors and conduct attribution of sources.

Objectives This study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3–5 predialysis chronic kidney disease (CKD) patients. Design This study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis > 50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD. Results The adjusted odds ratios of CAD were 3.059 (95% CI: 1.859–5.032) and 2.670 (95% CI: 1.605–4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR = 1.177, 95% CI 1.067–1.299, P = 0.001) or TVD (adjusted OR = 1.154, 95% CI 1.076–1.238, P Conclusions FAR levels were independently associated with the presence and severity of CAD in stage 3–5 predialysis CKD patients.

The rapid depletion of oxygen during irradiation at ultra-high dose rate calls for tissue oximeters capable of high temporal resolution. This study demonstrates a water-soluble phosphorescent nanoprobe and fiber-coupled instrument, which together are used to measure the kinetics of oxygen depletion at 200 Hz during irradiation of in vitro solutions.

3α-HSDHs have a crucial role in the bioconversion of steroids, and have been widely applied in the detection of total bile acid (TBA). In this study, we report a novel NADP(H)-dependent 3α-HSDH (named Sc 3α-HSDH) cloned from the intestinal microbiome of Ursus thibetanus. Sc 3α-HSDH was solubly expressed in E. coli (BL21) as a recombinant glutathione-S-transferase (GST)-tagged protein and freed from its GST-fusion by cleavage using the PreScission protease. Sc 3α-HSDH is a new member of the short-chain dehydrogenases/reductase superfamily (SDRs) with a typical α/β folding pattern, based on protein three-dimensional models predicted by AlphaFold. The best activity of Sc 3α-HSDH occurred at pH 8.5 and the temperature optima was 55 °C, indicating that Sc 3α-HSDH is not an extremozyme. The catalytic efficiencies (k

With the ever-increasing burden of kidney disease, the need for developing new therapeutics to manage this disease has never been greater. Extracellular vesicles (EVs) are natural membranous nanoparticles present in virtually all organisms. Given their excellent delivery capacity in the body, EVs have emerged as a frontier technology for drug delivery and have the potential to usher in a new era of nanomedicine for kidney disease. This review is focused on why EVs are such compelling drug carriers and how to release their fullest potentiality in renal therapeutics. We discuss the unique features of EVs compared to artificial nanoparticles and outline the engineering technologies and steps in developing EV-based therapeutics, with an emphasis on the emerging approaches to target renal cells and prolong kidney retention. We also explore the applications of EVs as natural therapeutics or as drug carriers in the treatment of renal disorders and present our views on the critical challenges in manufacturing EVs as next-generation renal therapeutics.

Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS).An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated.The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16).Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Holmquist Johnson Cook (HJC) model has been extensively adopted to simulate the projectile penetration of concrete targets. In this study, based on the available experimental data of uniaxial compression, triaxial compression, split Hopkinson pressure bar (SHPB) and Hugoniot tests, HJC model parameters in terms of the strength surface, strain rate effect, damage evolution and equation of state (EOS) were systematically calibrated for a newly fabricated ultra-high performance concrete termed as geopolymer-based ultra-high performance concrete (G-UHPC). Using the HJC model with calibrated model parameters, numerical simulations of projectile penetration into plain and fibre reinforced G-UHPC targets were performed in a commercial finite element program LS-DYNA. The numerical results for the depth of penetration (DOP) exhibited fair agreement with the test data. The numerical projectile velocity and displacement evolutions were also validated through comparing to the semi-analytical model. These observations demonstrated the applicability and validity of the calibrated HJC model to estimate DOP of G-UHPC targets subjected to projectile impact. With the calibrated and validated HJC model, parametric studies were further conducted to explore the effect of uniaxial compressive strength of G-UHPC, projectile impact velocity, mass, diameter and nose shape on the final DOP values. Based on the numerical results from the parametric studies, an empirical equation concerning the aforementioned variables was proposed, which could help design G-UHPC protective barriers against projectile penetration.

Wheat powdery mildew is a destructive disease seriously threatening yield and quality. Comprehensive dissection of new resistance-related loci/genes is necessary to control this disease. LS5082 is a Chinese wheat breeding line with resistance to powdery mildew. Genetic analysis indicated that a single dominant gene, tentatively designated PmLS5082, conferred seedling resistance to different Bgt isolates. Bulked segregant RNA-seq (BSR-seq) was carried out to map the R gene PmLS5082 and profile differentially expressed genes associated with PmLS5082. PmLS5082 was mapped to chromosome arm 2BL and flanked by the markers WGGBH612-5 and YTU19-005 with genetic distances of 0.3 and 0.4 cM, respectively. The physical position was subsequently locked into the interval of 710.3-711.0 Mb. PmLS5082 differs from the catalogued Pm genes on chromosome arm 2BL in its resistant spectrum, physical position and origin, suggesting it is most likely a new Pm gene. Through COG and KEGG analysis, differentially expressed genes associated with PmLS5082 were profiled, and six genes in PmLS5082 interval were confirmed to be associated with PmLS5082 via RT-qPCR, using an additional set of wheat samples and time-course analysis post-inoculation with Bgt. In order to transfer PmLS082 to different genetic backgrounds using marker-assisted selection (MAS), closely linked markers, including Kompetitive Allele-Specific PCR (KASP) markers, were evaluated and nine markers were confirmed to be widely applicable for MAS in different genetic backgrounds.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.