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OBJECTIVES The aim of this study was to investigate whether higher serum uric acid (SUA) levels within the physiological range were associated with changes in lumbar spine bone mineral density (LBMD) in postmenopausal women without existing lumbar spine osteoporosis after a longitudinal follow-up of 3.09 years, and to further confirm the relationship between SUA and bone mineral density (BMD) in other sites such as femoral neck, total hip, and trochanter at follow-up. METHODS A longitudinal study of 175 healthy postmenopausal women without osteoporosis was conducted in Shenyang, China. BMD of the lumbar spine, femoral neck, total hip, and trochanter were measured using dual-energy x-ray absorptiometry at each visit. Pearson's correlation analysis and regression analyses were performed to determine any associations. RESULTS There were positive correlations between baseline SUA and BMD of the lumbar spine (P = 0.03), total hip (P = 0.04), and trochanter (P = 0.04). Moreover, higher baseline SUA levels were independently associated with LBMD decline and the odds ratio of the baseline SUA of the third quartile group was 0.12 (95% confidence interval, 0.02-0.70, P

Background: Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial.Methods: The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis.Results: Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, P = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, P = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat.Conclusion: Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.

Xinning Wang,1 Qiang Zu,1 Jinshan Lu,1 Lei Zhang,1 Qiang Zhu,1 Xuefeng Sun,2 Jun Dong1 1Department of Urology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Nephrology, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuefeng Sun; Jun Dong Email xfssun@126.com; jundong@vip.126.comIntroduction: Our previous study revealed that a young internal environment ameliorated kidney aging by virtue of an animal model of heterochronic parabiosis and a model of heterochronic renal transplantation. In this research, we used proteome to investigate the effects of donor-recipient age difference in clinical renal transplantation.Methods: This study included 10 pairs of renal transplantation donors and recipients with an age difference of greater than 20 years to their corresponding recipients/donors. All recipients have received transplantation more than 3 years ago. Renal function and the serum/urine proteomes of the donors and recipients were analyzed.Results: The renal function was similar between the young recipients and the old donors. In contrast, the renal function of the young donors was significantly superior to that of the old recipients. Furthermore, 497 and 975 proteins were identified in the serum and urine proteomes, respectively. The content of SLC3A2 in the blood was found to be related to aging, while the contents of SERPINA1 and SERPINA3 in the urine were related to immune functions after renal transplantation.Conclusion: This study demonstrated that, in the human body, a younger internal environment could ameliorate kidney aging and provided not only clinical evidence for increasing the age limit of kidney transplant donors but also new information for kidney aging research.Keywords: renal transplantation, aging, proteome, living donor transplantation

The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2′-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.

Disinfection is an indispensable water treatment process for killing harmful pathogens and protecting human health. However, the disinfection has caused significant public concern due to the formation of toxic disinfection by-products (DBPs). Lots of studies on disinfection and DBPs have been performed in the world since 1974. Although related studies in China started in 1980s, a great progress has been achieved during the last three decades. Therefore, this review summarized the main achievements on disinfection and DPBs studies in China, which included: (1) the occurrence of DBPs in water of China, (2) the identification and detection methods of DBPs, (3) the formation mechanisms of DBPs during disinfection process, (4) the toxicological effects and epidemiological surveys of DBPs, (5) the control and management countermeasures of DBPs in water disinfection, and (6) the challenges and chances of DBPs studies in future. It is expected that this review would provide useful information and reference for optimizing disinfection process, reducing DBPs formation and protecting human health.

The occurrence of multi-modal ages for inclusions contained within cave sediments is probably far more widespread and problematic than has been appreciated by archaeologists until now. This phenomenon is likely to be a relatively common situation in caves especially in tropical/sub-tropical areas like southern China where karstification and sedimentation would have been rapid within a context of active hydrological regimes over protracted periods during the Pleistocene. The availability of various cost-effective dating techniques applicable to both Pleistocene cave sediments and a range of sedimentary inclusions means that archaeologists are now better placed to understand this phenomenon than ever before. Here we describe the results of Uranium-series dating of a randomly selected sample of deer bones and teeth from Maludong in southern China which demonstrate the existence of disparate multi-modal ages among sedimentary inclusions at the site. These results have implications for previous reconstructions of the palaeoenvironment of the site as well as for interpretations of the possible significance of enigmatic hominin remains from Maludong for understanding the late phases of human evolutionary history in the region. We conclude that the complexities of reconstructing sedimentary history and allied challenges of dating sedimentary inclusions in caves require urgent and serious attention by archaeologists especially in light of the growing international attention being paid to later Middle and Late Pleistocene sites in tropical East Asia.

Three-dimensional hollow SnO2@TiO2 spheres encapsulated in reduced graphene oxide aerogels (HSTGAs) were successfully fabricated through self-assembly from SnO2@TiO2 hollow spheres and graphene oxide nanosheets using a simple hydrothermal process. The hollow spheres possess an average size of 360 nm. The thickness of SnO2 shell is 10–15 nm, and the thickness of TiO2 shell is 20–35 nm. The TiO2 shell was anchored onto the surface of hollow SnO2 spheres to effectively limit volume change. Afterward, hollow SnO2@TiO2 spheres were wrapped in graphene oxide nanosheets to build a three-dimensional conductive structure. The applications of HSTGAs as anode for lithium ion storage were explored. Systematic electrochemical results show that HSTGAs electrode maintains a high-discharge capacity of about 668.2 mA h g−1 at 100 mA g−1 after 200 cycles. Compared with pure metal oxide hollow spheres, HSTGAs can greatly enhance the electrochemical performance due to the synergistic effects of metal oxide hollow spheres and graphene oxide nanosheets. HSTGAs are prospective multifunctional nanomaterials that can be used to solve the current energy storage issues.

Polyaniline (PANI) is a conducting polymer which has been employed as a photosensitizer for enhancing the performance of a number of photocatalysts. Herein, we describe the synthesis of organic–inorganic hybrid materials in order to enhance the photocatalytic activity of double-shell TiO2/PANI hollow spheres (TAHSs), which were fabricated by means of sol–gel and in situ polymerization processes. The physicochemical properties of the PANI-modified TiO2 hollow spheres were investigated by a variety of techniques. The effect of the PANI shell layer on the photocatalytic activity of TAHSs was elucidated. With the optimal PANI content, the resultant TiO2/PANI hybrid materials exhibited remarkably enhanced UV and visible light photocatalytic degradation of aqueous methyl orange, far exceeding the activity of bare TiO2 hollow spheres. The synergistic effect between TiO2 and PANI is explained in terms of the improved separation of photogenerated electron–hole pairs.

The Luonan Basin is a key region of early human settlement in Central China with more than 300 discovered Paleolithic sites. Artifact layer 1 of the Liuwan site was dated to approximately 0.6 million years (Ma) based on correlation with the well-dated loess–paleosol sequence of the central Chinese Loess Plateau. This study reassessed the age of the Liuwan artifact layer via an absolute dating method, namely, 26Al/10Be burial dating. We determined the burial age of artifact layer 1, which was most likely at least 0.60 ± 0.12 Ma (1ơ), using three simple burial ages. The new burial age confirmed the previous estimated age and provided a considerably accurate age range. Therefore, we suggest the use of the 26Al/10Be burial dating method in thin loess-covered Paleolithic sites around the Qinling Mountain Range is helpful to understand the early human behavior.

Sand-loess sequences in the desert-loess transition zone are sensitive terrestrial archives for recording past climatic changes and atmospheric dust activities. However, a high-resolution chronology for relative long-term sand-loess sequences is still rare. In this study, we used quartz SAR OSL and K-feldspar pIRIR (pIRIR290) methods to date a 16.8 m sand-loess sequence at Zhenbeitai in Yulin (North-Central China). The quartz is sensitive, fast component dominated but saturates at ∼150 Gy. The measured K-feldspar pIRIR290 De showed no dependency on the first IR stimulation temperature between 50 °C and 260 °C. Dose recovery results were consistent with unity up to ∼800 Gy for a test dose of approximately 30% of the equivalent dose to be measured. The resulting pIRIR290 ages are consistent with the stratigraphy up to ∼121 ka. Thus, a high-resolution chronology up to the last interglacial could be established for the Zhenbeitai sand-loess section. Derived mass accumulation rates show sedimentation rates of ∼10–80 cm/ka for the upper loess (

Low-temperature thermal conductivity (κ), as well as the magnetic properties and specific heat, are studied for the frustrated zigzag spin-chain material SrEr2O4 by using single-crystal samples. The specific heat data indicate the long-range antiferromagnetic transition at ∼ 0.73 K and the existence of strong magnetic fluctuations. The magnetizations at very low temperatures for magnetic field along the c axis (spin chain direction) or the a axis reveal the field-induced magnetic transitions. The κ shows a strong dependence on magnetic field, applied along the c axis or the a axis, which is closely related to the magnetic transitions. Furthermore, high magnetic field induces a strong increase of κ. These results indicate that thermal conductivity along either the c axis or the a axis are mainly contributed by phonons, while magnetic excitations play a role of scattering phonons.

An immunized mouse phage display scFv library with a capacity of 3.34 × 109 CFU/mL was constructed and used for screening of recombinant anti-ciprofloxacin single-chain antibody for the detection of ciprofloxacin (CIP) in animal-derived food. After four rounds of bio-panning, 25 positives were isolated and identified successfully. The highest positive scFv-22 was expressed in E. coli BL21. Then, its recognition mechanisms were studied using the molecular docking method. The result showed the amino acid residue Val160 was the key residue for the binding of scFv to CIP. Based on the results of virtual mutation, the scFv antibody was evolved by directional mutagenesis of contact amino acid residue Val160 to Ser. After the expression and purification, an indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) based on the parental and mutant scFv was established for CIP, respectively. The IC50 value of the assay established with the ScFv mutant was 1.58 ng/mL, while the parental scFv was 26.23 ng/mL, this result showed highly increased affinity, with up to 16.6-fold improved sensitivity. The mean recovery for CIP ranged from 73.80% to 123.35%, with 10.46% relative standard deviation between the intra-assay and the inter-assay. The RSD values ranged between 1.49% and 9.81%. The results indicate that we obtained a highly sensitive anti-CIP scFv by the phage library construction and directional evolution, and the scFv-based IC-ELISA is suitable for the detection of CIP residue in animal-derived edible tissues.

Martinon-Torres et al. (1) present a flawed reinterpretation of our work which demands correction. FY-HT-1 and FY-HT-2 were collected from the section walls of the 2011–2013 excavations; details of provenience were provided (2). All of the lingual and much of the occlusal and mesial surfaces of FY-HT-2’s enamel is missing (Fig. 1 A ). Therefore, reconstructions of “deer-like” wear (1) simply bear no resemblance to the preservational reality of the tooth. Also disconcerting is their comparison of FY-HT-2 with images of various deer incisors (Fig. 1 A and ref. 1). Confirmation bias aside, a proper comparison would have indicated affinities to recent humans (Fig. 1 A ), as confirmed by DNA analyses (2). Regarding FY-HT-1, its preservation is visually indistinct from existing samples (see ref. 3). But within-sample variation is clear, and expected, given nonuniform taphonomic processes within the context of a dynamic sedimentary history, as we have demonstrated at Fuyan Cave (2). Fig. 1. ( A ) Fuyan Cave tooth FY-TH-2 ( i ), a recent human from the Foyemiaowan Han Tomb ( ii ), and deer of Martinon-Torres et al. (1) ( iii ). Right column adapted with permission from ref. 1. ( B ) Number of sequences overlapping each position in the FY-HT-2 mitochondrial genome (coverage, Left ) and percentage of sequences carrying an identical base ( Right ). ( C ) Frequencies of nucleotide substitutions at the start and end positions of sequences from the FY-HT-2 library. Martinon-Torres et al. (1) and Higham and Douka (4) challenge our AMS 14C dating. We describe our accelerator mass spectrometry (AMS) 14 … [↵][1]1To whom correspondence may be addressed. Email: darrencurnoe{at}icloud.com. [1]: #xref-corresp-1-1

The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD.A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (12 years old: 2.5 g tid; 6∼12 years old: 1.5 g tid; 2∼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests.2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 mSingle-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.

Purpose Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from RM is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients. Method Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. We extracted data from the first 24 h after patient ICU admission. Data from the two data sets were merged for further analysis. The merged data sets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model. Results In total, 938 patients with RM were eligible for this analysis. The area under the receiver operating characteristic curve (AUC) of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915, and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression, AUC = 0.862; support vector machine, AUC = 0.843; random forest, AUC = 0.825; and naive Bayesian, AUC = 0.805) and clinical scores (Sequential Organ Failure Assessment, AUC = 0.747; Acute Physiology Score III, AUC = 0.721). Conclusions Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24 h of admission to the ICU.

Introduction Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes. Methods We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days. Results miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70–100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO. Conclusion miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.

The quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool. Here, we show that the muscle fiber maintains a continuum of quiescent states, through a gradient of Notch ligand, Dll4, produced by the fiber and captured by QSCs. The abundance of Dll4 captured by the QSC correlates with the protein levels of the stem cell (SC) identity marker, Pax7. Niche-specific loss of Dll4 decreases QSC diversity and shifts the continuum to cell states that are biased toward more proliferative and committed fates. We reveal that fiber-derived Mindbomb1 (Mib1), an E3 ubiquitin ligase activates Dll4 and controls the heterogeneous levels of Dll4. In response to injury, with a Dll4-replenished niche, the normal continuum and diversity of the SC pool is restored, demonstrating bidirectionality within the SC continuum. Our data show that a post-translational mechanism controls heterogeneity of Notch ligands in a multinucleated niche cell to maintain a continuum of metastable states within the SC pool during tissue homeostasis.

Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U–Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS (14)C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS (14)C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Invited for the cover of this issue is Qinghua Gong, Guowei Zhou, and co-workers at Qilu University of Technology. The dial represents the etching time of SiO

BackgroundRhabdomyolysis (RM) is a clinical syndrome characterised by the breakdown of skeletal muscle fibres and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous study, exogenous biological renal support alleviates renal ischaemia-reperfusion injury (IRI) in elderly mice. This study aimed to determine whether exogenous biological renal support promoted renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved.MethodsA parabiosis animal model was established to investigate effects of exogenous biological renal support on RM-induced AKI. Male wild-type C57BL/6 mice and C57BL/6-TgN (ACTb-EGFP) transgenic mice were used to determine whether shared circulation was established among parabiotic pairs 3 weeks after parabiosis surgery. Mice were divided into three groups: the control group (sterile saline injected); RM group (glycerol (8 mL/kg) injected); and parabiosis + RM group (three weeks after the parabiosis model was established, the recipient mouse was injected with glycerol). Blood samples and kidney tissue were collected for further processing 48 hours after RM induction. Bioinformatics analysis was conducted with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, functional enrichment analysis and clustering analysis.ResultsAt 48 hours after the procedure, all mice survived. Exogenous biological renal support attenuated the histological and functional deterioration in RM-induced AKI in mice. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated kidney injury through multiple pathways, including suppressing the complement system; attenuating oxidative stress, inflammation, and apoptosis; and increasing proliferation.ConclusionsExogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and apoptosis; and promoting tubular cell proliferation. Our study provides new ideas for effectively preventing and treating RM-induced AKI and provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.

Introduction Rhabdomyolysis (RM) is a complex set of clinical syndromes involving the rapid dissolution of skeletal muscles. The early detection of patients who need renal replacement therapy (RRT) is very important and may aid in delivering proper care and optimizing the use of limited resources. Methods Retrospective analyses of the following three databases were performed: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care III (MIMIC-III) database and electronic medical records from the First Medical Centre of the Chinese People's Liberation Army General Hospital (PLAGH). The data from the eICU-CRD and MIMIC-III datasets were merged to form the derivation cohort. The data collected from the Chinese PLAGH were used for external validation. The factors predictive of the need for RRT were selected using a LASSO regression analysis. A logistic regression was selected as the algorithm. The model was built in Python using the ML library scikit-learn. The accuracy of the model was measured by the area under the receiver operating characteristic curve (AUC). R software was used for the LASSO regression analysis, nomogram, concordance index, calibration, and decision and clinical impact curves. Results In total, 1259 patients with RM (614 patients from eICU-CRD, 324 patients from the MIMIC-III database and 321 patients from the Chinese PLAGH) were eligible for this analysis. The rate of RRT was 15.0% (92/614) in the eICU-CRD database, 17.6% (57/324) in the MIMIC-III database and 5.6% in the Chinese PLAGH (18/321). After the LASSO regression selection, eight variables were included in the RRT prediction model. The AUC of the model in the training dataset was 0.818 (95% CI 0.78–0.87), the AUC in the test dataset was 0.794 (95% CI 0.72–0.86), and the AUC in the Chinese PLAGH dataset (external validation dataset) was 0.820 (95% CI 0.70–0.86). Conclusions We developed and validated a model for the early prediction of the RRT requirement among patients with RM based on 8 variables commonly measured during the first 24 h after admission. Predicting the need for RRT could help ensure appropriate treatment and facilitate the optimization of the use of medical resources.

Background: youthful blood environment was shown to decelerate the aging process of kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. To further investigate the effect of youthful blood environment on renal interstitial fibrosis and the underlying mechanisms, we bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries.Methods: Parabiotic mice were divided into isochronic parabiotic (young-young, Y-IP and old-old, O-IP) and heterochronic parabiotic (young-old, HP) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice. Results: Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with wildtype UUO mice, the expressions of pNF-κB and fibrosis-related proteins, kidney interstitial fibrosis area, and the kidney function were all significantly decreased in Wps/Wps UUO mice.Conclusions: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice, and ameliorated UUO-induced kidney fibrosis and function loss, which may be mediated via the NF-κB pathway.

SummaryThe quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool. Here we show that the muscle fiber maintains a continuum of quiescent states, through a gradient of Notch ligand, Dll4, produced by the fiber and captured by QSCs. The abundance of Dll4 captured by the QSC correlates with levels of the SC identity gene, Pax7. Niche-specific loss of Dll4 decreases QSC diversity and shifts the continuum, towards more proliferative and committed states. We reveal that fiber-derived Mindbomb1 (Mib1), an E3 ubiquitin ligase activates Dll4 and controls the spatial localization of Dll4. In response to injury, with a Dll4-replenished niche, the normal continuum and diversity of SC pool is restored, demonstrating bi-directionality within the SC continuum. Our data shows that a post-translational mechanism controls spatial heterogeneity of Notch ligands in a multinucleated niche cell to maintain a continuum of diverse states within the SC pool during tissue homeostasis.

At present, lithium-ion batteries (LIBs) have received widespread attention as substantial energy storage devices, thus, their electrochemical performances must be continuously researched and improved. In this paper, we demonstrate a simple self-template solvothermal method combined with annealing for the synthesis of NiFe2O4 yolk-shell (NFO-YS) and NiFe2O4 solid (NFO-S) nanospheres by controlling the heating rate and coating them with a carbon layer on the surface via high-temperature carbonization of resorcinol and formaldehyde resin. Among them, NFO-YS@C has an obvious yolk-shell structure, with a core-shell spacing of about 60 nm, and the thicknesses of the NiFe2O4 shell and carbon shell are approximately 15 and 30 nm, respectively. The yolk-shell structure can alleviate volume changes and shorten the ion/electron diffusion path, while the carbon shell can improve conductivity. Therefore, NFO-YS@C nanospheres as the anode materials of LIBs show a high initial capacity of 1087.1 mA h g&minus, 1 at 100 mA g&minus, 1, and the capacity of NFO-YS@C nanospheres impressively remains at 1023.5 mA h g&minus, 1 after 200 cycles at 200 mA g&minus, 1. The electrochemical performance of NFO-YS@C is significantly beyond NFO-S@C, which proves that the carbon coating and yolk-shell structure have good stability and excellent electron transport ability.

Background Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions. Methods A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections. Discussion At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research. Trial registration Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated the high expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) from old rats, which mediated the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.Methods: miR-133b expression induced during the EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and time points (0, 24, 48, and 72 h) was detected using real-time polymerase chain reaction. The target genes of miR-133b were validated using a dual-luciferase reporter assay. In vitro experiments were performed to observe mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-week-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. miR-133b、 target gene and other indexes mentioned above mRNA and protein levels and renal interstitial fibrosis were detected at 7 and 14 days.Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. Dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. miR-133b mimic transfection inhibited the TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidneys after injection of the miRNA-133b overexpression complex, significantly alleviating renal interstitial fibrosis in UUO mice.Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, consequently reducing the TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in old UUO mice.

Background: The complications of coronavirus disease 2019 (COVID-19) involved multiple organs or systems, especially in critically ill patients. We aim to investigate the neurological complications in critically ill patients with COVID-19. Methods: This retrospective single-center case series analyzed critically ill patients with COVID-19 at the intensive care unit of Tongji Hospital, Wuhan, China from February 5 to April 2, 2020. Demographic data, clinical and laboratory findings, comorbidities and treatments were collected and analyzed. Results: Among 86 patients with confirmed COVID-19, 54 patients (62.8%) were male, and the mean (SD) age was 66.6 (11.1) years. Overall, 65% patients presented with at least one neurological symptom. Twenty patients (23.3%) had symptoms involving the central nervous system, including delirium, cerebrovascular diseases and hypoxic-ischemic brain injury, while 6 patients (7%) had neuromuscular involvement. Seven of 86 patients exhibited new stroke and 6 (7%) cases were ischemic. A significantly higher prevalence of antiphospholipid antibodies was observed in patients with ischemic stroke than in those without stroke (83.3 vs. 26.9%, p < 0.05). Patients with ischemic stroke were more likely to have a higher myoglobulin level, and a lower hemoglobin level. Conclusions: The clinical spectrum of neurological complications in critically ill patients with COVID-19 was broad. Stroke, delirium and neuromuscular diseases are common neurological complications of COVID-19. Physicians should pay close attention to neurological complications in critically ill patients with COVID-19.

Ecological degradation impedes sustainable development in Southwest China, and artificial afforestation has been a key strategy of the Government of China to effectively curb it. However, the water consumed by large-scale afforestation has a huge impact on water supply in Southwest China, which also arise a new challenge causing severe drought here recently. In order to determine the impact of artificial afforestation on the region, this study conducts spatiotemporal, abrupt change, and correlation and regression analyses. Results show that although water resources fluctuate, they exhibit a general declining trend. Especially after 2000, water resources showed a significant downward trend. In terms of spatial tendency, there has been an obvious decrease in water resources in the Sichuan Basin, the mountainous region of eastern Chongqing, and the Yunnan–Guizhou Plateau. Due to extensive afforestation and vegetation cover growth, there has been an increase in most trends of forest-shrub ecosystems, resulting in substantially enhanced evapotranspiration effects. The uptake of water by afforestation in Southwest China could reach 40.42 billion m3, which is equivalent to 10.69% of its annul available water supply (1980–2015). Generally, afforestation disrupts the water balance of the region. This study recommends substituting afforestation for natural restoration or, at the very least, selecting vegetation that requires less water for the restoration of the ecological environment of Southwest China, which provide scientific method for regional sustainable development.

Introduction Over the past few decades, the incidence of Rhabdomyolysis (RM) has significantly increased. The prognosis is substantially worse if renal failure develops. Many problems remain to be addressed regarding the pathogenesis, prevention, and treatment of RM. The purpose of this study was to identify and characterize the top 100 most cited publications regarding rhabdomyolysis (RM) by performing a bibliometric analysis. Methods Publications focusing on RM were identified from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC). Bibliographic information was collected, including year of publication, authorship, publishing journals, institution, country of origin and keywords. CiteSpace V5.6.R2 and the Online Analysis Platform of Literature Metrology were used for descriptive analysis. Results The 100 most cited articles were published between 1995 and 2016, with citation numbers ranging from 116 to 904. The United States (60) has been the largest contributor to RM research. Hartford Hospital and University of Texas were found to be the most productive institutions, with five articles each. Thompson, PD, who authored six articles, was the most productive author. The American Journal of Cardiology published the most articles (5), followed by the New England Journal of Medicine (4). The top three co-cited journals were the New England Journal of Medicine (74), Lancet (59) and JAMA (54). Conclusions This study provides valuable information on the study of RM. These findings may be used to guide clinical decision-making and identify new research fields.

An isostructural phase transition and a cubic to tetragonal phase transition in spin-frustrated pyrochlore Dy

Purpose. To investigate the factors influencing brachial-ankle pulse wave velocity (baPWV) in an apparently healthy Chinese population, especially the associations between baPWV and indices of blood pressure (BP). Methods. A total of 1123 participants with no history of hypertension were enrolled in this study, and the baPWV and BP of all four limbs were measured along with other covariates. Correlation analyses and multivariate linear regression models were used to identify factors associated with baPWV. Results. A total of 1123 participants (male 43.3%, mean age: 58.4±13.9 years) were included. The average baPWV was 14.87±3.21 m/s, and no difference was found between the sexes. Age was positively correlated with baPWV (r=0.65, p<0.01), especially in females (r=0.71 versus 0.56 in males). The correlation coefficient between age and baPWV increased markedly after the age of 65 years. In addition, the resting heart rate (RHR), waist-hip ratio, glomerular filtration rate, and plasma glucose level were significantly correlated with baPWV (r=0.25, 0.22, -0.43, and 0.25, respectively; p<0.01). BP parameters were highly positively correlated with baPWV, especially systolic BP (SBP) and pulse pressure (PP). Multivariate regression revealed that age, BP parameters, and RHR were independently correlated with baPWV (p<0.01) after adjusting for confounding factors. The standardized coefficients of SBP were greater than those of PP, followed by diastolic BP (DBP). Conclusion. BaPWV increased with age, especially after 65 years. Age, BP, and RHR were independent factors associated with baPWV. The effect of SBP on baPWV was more prominent than that of PP.

Additional file 1. Questionnaire used in this study.

Background: Coronavirus 2019 (COVID-19) first emerged in Wuhan, China in December 2019, but spread rapidly throughout the world and became a pandemic Critical

Additional file 3. Detailed process of derivation and validation of the prediction rule.

Additional file 1: Table S1. Quality of eligible studies.

Image reconstruction based on deep learning has become an effective tool in fluorescence microscopy. Most deep learning reconstruction methods ignore the mechanism of the imaging process where a large number of datasets are required. In addition, a lot of time is spent solving the aliasing problem from multi-scaled image pairs for data pre-processing. Here we demonstrate an improved generative adversarial network for image scanning microscopy (ISM) that can be trained by simulation data and has good generalization. Based on physical imaging models, this method can generate matching image pairs from simulation images and uses them as datasets for network training, without capturing a large number of real ISM images and avoiding image alignment preprocessing. Simulation and experimental results show that this simulation data-driven method improves the imaging quality of conventional microscopic images and reduces the cost of experiments. This method provides inspiration for optimizing network generalizability of the deep learning network.

Tremella-like silica spheres (TSSs) and brush-like silica fibers (BSFs) with well-defined structures were synthesized using cetyltrimethylammonium bromide and sodium dodecyl sulfate aggregate as structure-directing agent and β-cyclodextrin (β-CD) as inducing agent. By controlling the amount of β-CD, the morphology of mesoporous silica was changed from TSSs to BSFs and then back to TSSs. The materials were characterized by using several techniques. The extraordinary mesoporous silica with a brush-like shape and measuring 180–220 nm wide and 6–20 μm long were formed as a result of the diameter of the U-shaped silica skeleton. These two kinds of materials can be used as fluorescent hybrid materials by immobilizing Rhodamine B (Rh B). Furthermore, the hybrid materials were well characterized by the fluorescence spectra to prove that BSFs-Rh B has excellent fluorescence property.

Interstitial iron ( Fe i ) has strong influence on physical properties of Fe 1 + x Sb (0.08 ⩽ x ⩽ 0.38) compounds. We synthesized Fe 1.08 Sb single crystals with Fe i content close to the lower limit of solution area and investigated its transport and magnetic properties. The ac susceptibility and field dependence of magnetization measurements demonstrate that the transition at ∼9 K is a spin glass transition. By analyzing temperature dependence of susceptibility ( χ vs T) and resistivity (d2 ρ /dT2 vs T) results, we found a change of scattering in transport properties caused by the ordering of Fe i moments in this compound. In addition, the Hall resistivity results reveal that the hole-type carrier is dominant and the topological Hall effect induced by spin chirality is negligible in Fe 1.08 Sb.

The Qinling Mountain Range (QMR) in central China encompasses innumerable Paleolithic sites. The hominin settlement in the QMR is comparable with that in the Nihewan Basin in northern China. The recorded information on the loess deposition in the QMR include both hominin remains and environmental changes. Since 2004, geological, geomorphological, archaeological, and chronological investigations were conducted by our team. By systematically using luminescence, paleomagnetic, and 26Al/10Be burial dating methods to obtain age controls, and by correlating the pedostratigraphy and magnetic susceptibility of the Luochuan loess section, we established the loess–paleosol sequence and chronology of the lithic artifact levels for 35 Paleolithic sites and spots in the QMR. This work remarkable found shifts from glacial-to interglacial-driving hominin settlement patterns. During the stage between 1.2 and 0.7 Ma, large drying events, such as L15 (MIS 38) and L9 (MIS 22, 23 and 24), may have driven hominin migrations when the Loess Plateau was depopulated; moreover, the southern QMR was a glacial refugium. During the stage after ∼0.60 Ma, the contrasts between glacial and interglacial scales are the greatest; furthermore, longer and warmer humid interglacial environments were dominant. S5 (MIS 13, 14, 15) and S1 (MIS 5) interglacial periods provided the optimal environments for hominin settlement and dispersal. On the basis of investigations, we also found that the hominin settlement is relatively continuous from ∼1.20 Ma to ∼0.05 Ma in the QMR. The human occupation of the QMR decreased considerably after ∼0.05 Ma, probably because of changes in climate and human adaptations.

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis. However, there was no increase in autophagy. Compared to old mice with IRI, old-old parabiosis mice with IRI did not show differences in renal histological damage, oxidative stress, inflammation, apoptosis, or autophagy, but did exhibit improved renal function. Compared to the old-old parabiosis mice with IRI, the old mice with IRI in the young (12 week)-old parabiosis showed less renal histological injury and better renal function. Renal oxidative stress, inflammation, and apoptosis were significantly decreased, and autophagy was significantly increased. Thus, a youthful systemic milieu may decrease oxidative stress, inflammation, and apoptosis, and increase autophagy in old mice with IRI. These effects ameliorated IRI injuries in old mice. Our study provides new ideas for effectively preventing and treating AKI in the elderly.

We established a young (Y)-old (O) rat kidney transplantation model. With this model, we detected no age-related differences in renal structure between Y→Y and Y→O kidneys or O→O and O→Y kidneys. However, we did detect differences in levels of the senescence markers β-gal and p16 as well as the inflammatory cytokines TNF-α and IL-1β. Using proteomics analysis we detected 66 proteins associated with suppression of aging and 73 proteins associated with enhancement of aging. After construction of a protein-protein interaction network, a total of 73 nodes and 99 edges were analyzed using MCODE, and three significant modules were selected. GO and KEGG analyses showed that these proteins were mainly located in mitochondria and were largely related to oxidative stress. Among them, SOD1 expression was lower in Y→O than Y→Y kidneys and higher in O→Y than O→O kidneys. Acetylated (Ac)-NF-κB showed the opposite expression profile. In addition, SOD1 expression was higher in primary tubular epithelial cells from young rats than old rats, and SOD1 knockdown led to increased Ac-NF-κB expression. These findings suggest the local renal environment, particularly oxidative stress/mitochondrial function, affects renal aging.

Purpose The purpose of the study was to test the psychometrical properties of the Chinese version of the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire. Methods We translated the English version of the PEmb-QoL into Chinese. Patients at various periods after pulmonary embolism diagnosed at Peking Union Medical College Hospital between May 2016 and Dec 2017 were invited to complete the questionnaire. Standard psychometrical tests and criteria were used to evaluate the acceptability, reliability and validity of the Chinese version of the PEmb-QoL. Results A total of 108 participants completed the questionnaire and were included for further analysis. The Chinese version of the PEmb-QoL showed good internal consistency (Crohnbach's alpha ranging from 0.643 to 0.930), inter-item correlations (0.369–0.599), and item-total correlations (0.341–0.893). Test-retest reliability was also good (0.759–0.896). Moderate correlations between PEmb-QoL and SF-36 dimensions, and low correlations between PEmb-QoL and clinical characteristics supported convergent and discriminant validity. Exploratory factor analysis suggested four underlying dimensions: work-related problems, daily activity limitations, emotional complaints and frequency and intensity of complaints. Conclusions The Chinese version of the PEmb-QoL questionnaire is both valid and reliable for measuring quality of life in patients at various periods after pulmonary embolism, proving the universality of this disease-specific questionnaire.