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Sunitinib offers a significant survival benefit to patients with imatinib-resistant gastrointestinal stromal tumors (GIST). However, the incidence and risk of sunitinib-induced hematologic toxicities in such a population are often overlooked and have not been well characterized. This meta-analysis was performed to assess the summary incidence and risk of hematologic toxicities secondary to sunitinib in patients with GIST.Searches were performed in PubMed, Embase, Cochrane Library, and Web of Science as well as ClinicalTrials.gov to identify relevant studies up to April 2022. Studies with adequate safety profile, including anemia, neutropenia, and thrombocytopenia, were included to calculate the pooled incidence, relative risk (RR), and corresponding 95% confidence intervals (CIs). This study was registered with PROSPERO under number CRD42022328202.A total of 2593 patients from 13 studies were included in the present meta-analysis. For patients with GIST assigned to sunitinib, the overall incidences of all-grade anemia, neutropenia, and thrombocytopenia were 26.2% (95% CI, 14.9-39.4%), 41.8% (95% CI, 29.0-55.1%), and 36.4% (95% CI, 22.8-51.1%), respectively. Regarding high-grade (grades 3 and 4) events, there were 4.7% (95% CI, 3.8-5.6%) for anemia, 9.3% (95% CI, 5.6-13.7%) for neutropenia and 5.0% (95% CI, 2.9-7.3%) for thrombocytopenia. Compared to placebo arms, sunitinib was related to an increased risk of high-grade neutropenia with an RR of 10.39 (95% CI, 1.53-70.72; p = 0.017).Sunitinib carries a relatively high incidence of hematologic toxicities and a substantial increased risk of high-grade neutropenia in patients with GIST. Appropriate prevention and management seem to be inevitable.

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. FTO is an N6-methyladenosine (m6A) demethylase that participates in various biological events, while its role in DR remains elusive. Herein, we detected elevated FTO expression in retinal proliferative membranes of DR patients. FTO promoted endothelial cell (EC) cell cycle progression and tip cell formation to facilitate angiogenesisin vitro, in mice and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegenerationin vivoandin vitro. Mechanistically, FTO affected EC features via modulatingCDK2mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate mediated histone lactylation. FB23-2, an inhibitor to FTO’s m6A demethylase activity, suppressed angiogenic phenotypesin vivoandin vitro. Noteworthy, we developed a nanoplatform encapsulating FB23-2 for systemic administration, and confirmed its targeting and therapeutic efficiencies in mice. Collectively, our study demonstrated that FTO coordinates EC biology and retinal homeostasis in DR, providing a promising nanotherapeutic approach for DR.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life.Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated.Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21–3.01), significantly higher than in the MTX group 2.06 (1.81–2.32), p < 0.0001), and the median (IQR) β-CTX in the JBQG group was 0.4 (0.32–0.43), significantly lower than in the MTX group 0.55 (0.47–0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1–3), a decrease from 3 (2–4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1–2), a decrease from 2 (1–2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8–16), significantly lower than in the MTX group 26 (16–30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12–20), with a significant difference compared to the MTX group 19 (13–25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10–18), with a significant difference compared to the MTX group 16 (11–22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05).Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.

Rare earth-doped upconversion nanoparticles (UCNPs) have the advantages of a narrow emission peak, large anti-Stokes displacement, negligible autofluorescence and photobleaching, which make them popular in biomedical fields. With the development of biological technology and nanotechnology, great progress has been achieved in use of rare earth-doped UCNPs in the treatment and diagnosis of various diseases. To date, based on the light conversion characteristics of upconverted rare earth nanocrystals, their medical applications are mainly focused on the detection and treatment of tumors. In view of the above situation, this paper focuses on reviewing UCNPs applications for the treatment and detection of various diseases, including atherosclerosis, inflammation, bacterial infections, viruses, and tumors. Finally, challenges and opportunities regarding the use of UCNPs in diseases treatment and detection are discussed. Overall, our goal is to provide readers with a fresh perspective on recent developments in the treatment and detection of various diseases with rare earth-doped upconversion materials.

Gastrointestinal (GI) cancers, including colorectal cancer, pancreatic cancer, liver cancer and gastric cancer, are severe social burdens due to high incidence and mortality rates. Bromodomain and extra-terminal (BET) proteins are epigenetic readers consisting of four conserved members (BRD2, BRD3, BRD4 and BRDT). BET family perform pivotal roles in tumorigenesis through transcriptional regulation, thereby emerging as potential therapeutic targets. BET inhibitors, disrupting the interaction between BET proteins and acetylated lysines, have been reported to suppress tumor initiation and progression in most of GI cancers. In this review, we will demonstrate how BET proteins participate in the GI cancers progression and highlight the therapeutic potential of targeting BET proteins for GI cancers treatment.

Irreversible ion migration was utilized to design a built-in electric field and energy band bending in a symmetrically structured Au/FAPbBr3/Au device, which successfully leads to a self-powered photoelectric device based on FAPbBr3 crystals.

This paper investigates the kinematics and statics of a 3-UPU robot in screw coordinates. According to the definition of a twist, both the angular velocity of a rigid body and the linear velocity of a point on it are expressed in screw components. The twist equation is established to calculate the position and posture of each joint. This equation can be applied directly to analyze the statics. According to the definition of a wrench, both the force and torque of the planar linkages are expressed in wrench components. As a result, the wrench equations are established to express the resultant action of a force system in one coordinate frame. Compared with the traditional Cartesian coordinate method, the wrench equation is free from complex algebraic manipulation and convenient to obtain wrench matrix by Plücker coordinates of each wrench. Numerical calculation is applied to solve the kinematics which can conveniently depict the position and posture of each joint in the absolute coordinate frame. Six unknown variables can be solved with each equation of wrench that contains three forces and three torques. The kinematics and static analysis of the 3−UPU robot validate this method.

Background: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following exploratory abdominal laparotomy. Methods: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30 and 150 mg/kg) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) were measured at 24 h after surgery. Results: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions. Conclusions: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.

Additional file 2: Table S2. Demographic and clinical parameters of the study population.

Deploying deep learning models in cloud clusters provides efficient and prompt inference services to accommodate the widespread application of deep learning. These clusters are usually equipped with host CPUs and accelerators with distinct responsibilities to handle serving requests, i.e. generalpurpose CPUs for input preprocessing and domain-specific GPUs for forward computation. Recurrent neural networks play an essential role in handling temporal inputs and display distinctive computation characteristics because of their high inter-operator parallelism. Hence, we propose Chrion to optimize recurrent neural network inference by collaboratively utilizing CPUs and GPUs. We formulate the model deployment in the CPU-GPU cluster as an NP-hard scheduling problem of directed acyclic graphs on heterogeneous devices. Given an input model in the ONNX format and user-defined SLO requirement, Chrion firstly preprocesses the model by model parsing and profiling, and then partitions the graph to select execution devices for each operator. When an online request arrives, Chrion performs forward computation according to the graph partition by executing the operators on the CPU and GPU in parallel. Our experimental results show that the execution time can be reduced by 19.4% at most in the latency-optimal pattern and GPU memory footprint by 67.5% in the memory-optimal pattern compared with the execution on the GPU.

Supplemental material, sj-pdf-2-vmj-10.1177_1358863X221137617 for Regulation of oxidized LDL-induced proliferation and migration in human vascular smooth muscle cells by a novel circ_0007478/miR-638/ROCK2 ceRNA network by Zeyu Guan, Ran Lu, Yong Sun, Xiaogao Wang, Chaowen Yu and Tao Song in Vascular Medicine

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X221137617 for Regulation of oxidized LDL-induced proliferation and migration in human vascular smooth muscle cells by a novel circ_0007478/miR-638/ROCK2 ceRNA network by Zeyu Guan, Ran Lu, Yong Sun, Xiaogao Wang, Chaowen Yu and Tao Song in Vascular Medicine

Additional file 3: Fig S1. Ang-(1–7) and Ang II/Ang-(1–7) levels in the serum of each group of mice. Fig S2. Effect of Ang-(1–7) on LPS-mediated NF-κB nuclear translocation. Fig S3. Ang-(1–7) alleviates H9c2 cells apoptosis induced by LPS-mediated inflammatory response through the NF-κB and MAPK signaling pathways.

Additional file 1: Table S1. Baseline characteristics of patients who received trimodal therapy before and after PSM. Table S2. Univariate and multivariate analyses of OS in stage IIB-IVA patients who received trimodal therapy before and after PSM.

Few studies on the factors associated with multiloculated breast abscesses during lactation have been performed. We collected data on 1805 patients with breast abscesses during lactation, who were divided into single-cavity breast abscess (N = 1298) and multiloculated breast abscess groups (N = 507). Fifteen variables were compared between the groups. The results showed significant differences between the two groups in (1) whether in the puerperium, (2) separated from the baby > 12 h in the last week, (3) exclusively breastfeeding or not in the last 2 weeks, (4) inverted nipple on the affected side or not, (5) history of fever or not, (6) breast skin redness and swelling on the affected side or not, (7) nipple pain or not in the last 2 weeks, and (8) whether the breasts had been massaged by non-medical staff in the last month, with (1), (5), (6), and (8) being independent risk factors. Patients in the puerperium, separated from the baby, not exclusively breastfeeding, having an inverted nipple on the affected side, accompanied by fever, with breast skin redness and swelling on the affected side, nipple pain, and having undergone a breast massage by non-medical staff are more likely to develop multiloculated breast abscesses.

The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture’s actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS.

Summary Excessive water production from oil reservoirs not only affects the economical production of oil, but it also results in serious environmental concerns. Polymer gels have been widely applied to decrease water production and thus improve oil production. However, traditional polymer gels such as partially hydrolyzed polyacrylamide (HPAM)/chromium (III) gel systems usually have a short gelation time and cannot meet the requirement of some conformance control projects. This paper introduces a novel polymer gel system of which crosslinking time can be significantly delayed. A branched polymer grafted from arginine by the surface initiation method is synthesized as the backbone, chromium acetate is used as the crosslinker, and no additional additives are used for the gel system. The results show that the gelation time of this system can be delayed to 61 days at 45°C and 20 days at 65°C because of the rigid structure of the branched polymer and the excellent chromium (III) chelating ability of arginine. The polymer gels have been stable for more than 150 days at 45 and 65°C. Coreflooding and rheology tests have demonstrated that this branched polymer has good injectivity and shear resistance in high-permeability rocks.

Distilled grain waste (DGW) can be converted to organic fertilizer via aerobic composting process without inoculating exogenous microorganisms. To illustrate the material conversion mechanism, this study investigated the dynamic changes of bacterial community structure and metabolic function involved in DGW composting. Results showed that a significant increase in microbial community alpha diversity was observed during DGW composting. Moreover, unique community structures occurred at each composting stage. The dominant phyla were Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, Myxococcota, and Chloroflexi, whose abundance varied according to different composting stages. Keystone microbes can be selected as biomarkers for each stage, and Microbispora, Chryseolinea, Steroidobacter, Truepera, and Luteimonas indicating compost maturity. Co-occurrence network analysis revealed a significant relationship between keystone microbes and environmental factors. The carbohydrate and amino acid metabolism were confirmed as the primary metabolic pathways by metabolic function profiles. Furthermore, nitrogen metabolism pathway analysis indicated that denitrification and NH3 volatilization induced higher nitrogen loss during DGW composting. This study can provide new understanding of the microbiota for organic matter and nitrogen conversion in the composting process of DGW.

Aerobic composting is a promising alternative for the recycling of rice straw (RS), and an applicable nitrogen source is necessary to improve the process. The aim of this study was to compare the performance and microbial community dynamics of RS composting using urea or protein hydrolysate from leather waste (PHL) as a nitrogen source. Results showed that PHL addition achieved a faster temperature increase rate at start-up (1.85 ℃·h−1 vs 1.07 ℃·h−1), higher volatile solid degradation efficiency (48.04% vs 46.98%), and greater germination indices (111.72% vs 89.87%) in the end products, as compared to urea. The major bacterial phyla included Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria in both composting processes. Although the bacterial communities in both processes succeeded in a similar pattern according to different composting phases, PHL addition accelerated the succession rate of the microbial community. Co-occurrence network analysis revealed that bacterial community composition was strongly correlated with physicochemical properties such as dissolved organic carbon (DOC), NH4+, pH, temperature, and total nitrogen (TN) content. These results proved the potential of using PHL as a nitrogen source to improve the RS composting process.

Background and aims Mobile phone addiction (MPA) has recently aroused much attention due to its high incidence and considerable health hazards. Although some existing studies have documented that physical activity is negatively associated with MPA, it is little known about the potential effects underlying this relation. The aim of this study was to investigate the relationship between physical activity and MPA among undergraduates in China, and to further examine the moderating effect of exercise type in the relation between them. Methods By the quota sampling, a total of 650 participants engaged in this survey and completed relevant measurements including physical activity rating scale-3 (PARS-3) and mobile phone addiction tendency scale (MPATS). Results Gender (β = 0.271, P < 0.05) and major (β = −0.169, P < 0.05) could significantly predict MPA, respectively, and physical activity was an imperative protective factor to decrease MPA (β = −0.266, P < 0.001). While the physical activity level enhanced from none exercise to medium exercise, an optimum dose-response relationship would emerge between physical activity and MPA (F (3,604) = 4.799, P < 0.01). Most important, the relation between physical activity and MPA can be moderated by exercise type. Especially in terms of aerobic endurance exercise, the higher level of physical activity the undergraduates performed, the lower degree of MPA would be suffered by them (β = −0.266, P < 0.001). Discussion These findings could be conducive to better understand the positive and potential effects of physical activity on the intervention in MPA, and served as a persuasive evidence that as for university students, actively engaging in aerobic endurance exercise with the medium activity level would be a practicable exercise strategy to deal with MPA in daily lifestyle behavior.

Background: Acute kidney injury (AKI) is a significant public health problem with high morbidity and mortality. Unfortunately, no definitive treatment is currently available for AKI. RNA interference (RNAi) provides a new and potent method for gene therapy to tackle this dilemma. Methods We engineered red blood cell-derived extracellular vesicles (REVs) with targeting peptides and therapeutic siRNAs to treat experimental AKI in a mouse model following renal ischemia/reperfusion (I/R) injury and unilateral ureteral obstruction (UUO). Phage display identified peptides that bind to the kidney injury molecule-1 (Kim-1). RNA-sequencing (RNA-seq) characterized the transcriptome of ischemic kidney to explore potential therapeutic targets. Results REVs targeted with Kim-1-binding LTH peptide (REVLTH) efficiently homed to and accumulated at the injured tubules in kidney following I/R injury. We identified transcription factors P65 and Snai1 that drive inflammation and fibrosis as potential therapeutic targets. Taking advantage of the established REVLTH, siRNAs targeting P65 and Snai1 were efficiently delivered to ischemic kidney and consequently blocked the expression of P-p65 and Snai1 in tubules. Moreover, dual suppression of P65 and Snai1 significantly improved I/R- and UUO-induced kidney injury by alleviating tubulointerstitial inflammation and fibrosis, and potently abrogated the transition to chronic kidney disease. Conclusions A red blood cell-derived extracellular vesicle platform targeted Kim-1 in acutely injured mouse kidney and delivered siRNAs for transcription factors P65 and Snai1, alleviating inflammation and fibrosis in the tubules.

Background Urinary sediment messenger RNAs (mRNAs) have been shown as novel biomarkers of kidney disease. We aimed to identify targeted urinary mRNAs in diabetic nephropathy (DN) based on bioinformatics analysis and clinical validation. Methods Microarray studies of DN were searched in the GEO database and Nephroseq platform. Gene modules negatively correlated with estimated glomerular filtration rate (eGFR) were identified by informatics methods. Hub genes were screened within the selected modules. In validation cohorts, a quantitative polymerase chain reaction assay was used to compare the expression levels of candidate mRNAs. Patients with renal biopsy–confirmed DN were then followed up for a median time of 21 months. End-stage renal disease (ESRD) was defined as the primary endpoint. Multivariate Cox proportional hazards regression was developed to evaluate the prognostic values of candidate mRNAs. Results Bioinformatics analysis revealed four chemokines (CCL5, CXCL1, CXLC6 and CXCL12) as candidate mRNAs negatively correlated with eGFR, of which CCL5 and CXCL1 mRNA levels were upregulated in the urinary sediment of patients with DN. In addition, urinary sediment mRNA of CXCL1 was negatively correlated with eGFR (r = −0.2275, P = 0.0301) and CCL5 level was negatively correlated with eGFR (r = −0.4388, P Conclusions Urinary sediment CCL5 and CXCL1 mRNAs were upregulated in DN patients and associated with a decline in renal function and degree of renal interstitial fibrosis. Urinary sediment CCL5 mRNA could be used as a potential prognostic biomarker of DN.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-020-2873-1.

This work presents the study on solid-liquid mass transfer performance of suspension in a rotating packed bed (RPB). The calculation model of solid-liquid mass transfer coefficient (ks) is deduced on the basis of the mass conversation law. The ks in RPB is measured using the suspension of cation exchange resin particle reaction with NaOH. The effects of different operating parameters such as pre-dispersion time (t), rotating speed (N), mesh packing thickness (w), liquid volume flow rate (LT), and solid loading (e) are investigated. The results show that the ks increases with the increase of N and w, and increases first and then tends to remain constant with the increase of t and LT. However, the e has no influence on ks. The obtained ks ranges from 1.00×10-5 m/s to 2.60×10-4 m/s which is higher than that in microreactor (MR) under the similar experimental conditions.

Background There is no available viable treatment for Sepsis-Induced Cardiomyopathy (SIC), a common sepsis complication with a higher fatality risk. The septic patients showed an abnormal activation of the renin angiotensin (Ang) aldosterone system (RAAS). However, it is not known how the Ang II and Ang-(1–7) affect SIC. Methods Peripheral plasma was collected from the Healthy Control (HC) and septic patients and Ang II and Ang-(1–7) protein concentrations were measured. The in vitro and in vivo models of SIC were developed using Lipopolysaccharide (LPS) to preliminarily explore the relationship between the SIC state, Ang II, and Ang-(1–7) levels, along with the protective function of exogenous Ang-(1–7) on SIC. Results Peripheral plasma Ang II and the Ang II/Ang-(1–7) levels in SIC-affected patients were elevated compared to the levels in HC and non-SIC patients, however, the HC showed higher Ang-(1–7) levels. Furthermore, peripheral plasma Ang II, Ang II/Ang-(1–7), and Ang-(1–7) levels in SIC patients were significantly correlated with the degree of myocardial injury. Additionally, exogenous Ang-(1–7) can attenuate inflammatory response, reduce oxidative stress, maintain mitochondrial dynamics homeostasis, and alleviate mitochondrial structural and functional damage by inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thus alleviating SIC. Conclusions Plasma Ang-(1–7), Ang II, and Ang II/Ang-(1–7) levels were regarded as significant SIC biomarkers. In SIC, therapeutic targeting of RAAS, for example with Ang-(1–7), may exert protective roles against myocardial damage.

Purpose The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. Methods In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. Results After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to Conclusions Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

Common liver tissue damage is mainly due to the accumulation of toxic aldehydes in lipid peroxidation under oxidative stress. Cumulative toxic aldehydes in the liver can be effectively metabolized by acetaldehyde dehydrogenase 2 (ALDH2), thereby alleviating various liver diseases. Notably, gene mutation of ALDH2 leads to impaired ALDH2 enzyme activity, thus aggravating the progress of liver diseases. However, the relationship and specific mechanism between ALDH2 and liver diseases are not clear. Consequently, the review explains the relationship between ALDH2 and liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). In addition, this review also discusses ALDH2 as a potential therapeutic target for various liver diseases,and focuses on summarizing the regulatory mechanism of ALDH2 in these liver diseases.

Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-α regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia-reperfusion-, unilateral ureteral obstruction-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB, which plays a central role in the inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only under hypoxic conditions but also under normoxic conditions. Moreover, the induced HIF-1α by inflammation protected against tubular injury in AKI. Thus, our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.NEW & NOTEWORTHY Here, the mechanism of hypoxia-inducible factor-α (HIF-α) regulation in acute kidney injury (AKI) was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB was involved in the increasing expression of HIF-1α in AKI. Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription. Our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.

In this study, ZnSnO3/C nanofibers are successfully prepared using a simple electrospinning method and their morphology and electrical properties are characterized. The results show that the diameter of the ZnSnO3/C nanofibers is ~190 nm and they comprise ~25 nm particles. The lithium-ion battery (LIB) fabricated using the prepared ZnSnO3/C nanofibers exhibits a high initial specific capacity of 1411.7 mAh g−1 at a current density of 0.1 A g−1. Electrospun samples maintain a good specific capacity, owing to the unique structure of the ZnSnO3/C nanofibers, which provides both buffer spaces for the large volume expansion during repeated charge-discharge cycles and fast lithium-ion transport, resulting in excellent electrochemical performance. This study provides an effective method for the preparation of ZnSnO3/C nanofibers and a potential anode material for LIBs. ZnSnO3/C nanofibers are successfully synthesized via a simple electrospinning method, which maintains a good specific capacity during the charge discharge process with a large current density. These good performances are attributed to the unique structure of the ZnSnO3/C nanofibers, which provides both buffer spaces for the large volume expansion during repeated charge discharge cycles and fast lithium ion transport.