Early Famine Exposure Results in Left Ventricular Remodeled, Diastolic Dysfunction and Systolic Function Preserved in Adults.

INTRODUCTION: Malnutrition during a critical window of development in a fetus or infant can result in abnormal cardiac remodeling and function. It is uncertain whether the contribution of these effects continues to impact the cardiac remodeling and function of adults over the course of several decades of growth. Our study examined the impact of early Chinese famine exposure on cardiac remodeling, left ventricular (LV) diastolic function, and LV systolic function in adults. METHODS: Participants at high risk of cardiovascular disease from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project (PEACE MPP) were enrolled. The famine in China lasted from 1959 to 1962. A total of three groups were formed based on the participants' birth dates: pre-famine group, famine exposure group, and post-famine group. Logistic regression and linear mixed models were used to explore the association between famine exposure and cardiac remodeling, LV diastolic function and LV systolic function in adults. RESULTS: The study included 2,758 participants, the mean age was 57.05 years, 62.8% were female, 26.4% had LV hypertrophy (LVH), 59.6% had LV diastolic dysfunction (LVDD), and 10.5% had reduced global longitudinal strain (GLS). Compared to post-famine exposure, participants had independently increased risk of LVH in the famine exposure group (OR: 2.02, 95% CI: 1.60-2.56) and pre-famine exposure (OR: 1.36, 95% CI: 1.06-1.76). Compared to post-famine exposure, the risk of LVDD remarkably increased in the famine exposure group (OR: 3.04, 95% CI: 2.49-3.71) and pre-famine exposure group (OR: 1.87, 95% CI: 1.52-2.31). Famine exposure had no significant impact on GLS but was associated with a significant increase in LV ejection fraction (LVEF) and LV end-diastolic diameter (LVEDD). Significant interactions were observed between the effects of famine exposure and other clinical/sociodemographic variables (gender, systolic blood pressure [SBP] ≥140 mm Hg or not, high school or above or not, and annual income <50,000 RMB or not) on these outcomes. CONCLUSION: Exposure to famine, particularly during fetal and infant stages, increases the risk of LVH and LVDD in adults. However, the LV systolic function remains preserved. These impacts are more pronounced in females, individuals with SBP ≥140 mm Hg, those with low income, or those with high educational status.

Icariside II prevents kidney fibrosis development in chronic kidney disease by promoting fatty acid oxidation.

Renal interstitial fibrosis (RIF) is the main pathological basis for the progression of chronic kidney disease (CKD), however, effective interventions are limited. Here, we investigated the effect of Icariside II (ICA-II) on RIF and explored the underlying mechanisms. Rats receiving 5/6 ablation and infarction (A/I) surgery were gavaged with ICA-II (5 or 10 mg/kg) for 8 weeks. In vitro, TGF-ß1-stimulated NRK-52E cells were treated with ICA-II and (or) oleic acid, etomoxir, ranolazine, fenofibrate, and GW6471. The effects of ICA-II on RIF, fatty acid oxidation, lipid deposition, and mitochondrial function were determined by immunoblotting, Oil red O staining, colorimetric, and fluorometric assays. Using adeno-associated virus injection and co-culture methods, we further determined mechanisms of ICA-II anti-RIF. ICA-II ameliorated the fibrotic responses in vivo and in vitro. RNA-seq analysis indicated that ICA-II regulated fatty acid degradation and PPAR pathway in 5/6 (A/I) kidneys. ICA-II attenuated lipid accumulation and up-regulated expression of PPARα, CPT-1α, Acaa2, and Acadsb proteins in vivo and in vitro. Compared to ICA-II treatment, ICA-II combined with Etomoxir exacerbated mitochondrial dysfunction and fibrotic responses in TGF-ß-treated NRK-52E cells. Importantly, we determined that ICA-II improved lipid metabolism, fatty acid oxidation, mitochondrial function, and RIF by restoring PPARα. Co-culture revealed that ICA-II decreased the expression of Fibronectin, Collagen-I, α-SMA, and PCNA proteins in NRK-49F cells by restoring PPARα of renal tubular cells. ICA-II may serve as a promising therapeutic agent for RIF in 5/6 (A/I) rats, which may be important for the prevention and treatment of CKD.

Recent advances in the detection of pathogenic microorganisms and toxins based on field-effect transistor biosensors.

In food safety analysis, the detection and control of foodborne pathogens and their toxins are of great importance. Monitoring of virus transmission is equally important, especially in light of recent findings that coronaviruses have been detected in frozen foods and packages during the current global epidemic of coronavirus disease 2019. In recent years, field-effect transistor (FET) biosensors have attracted considerable scholarly attention for pathogenic microorganisms and toxins detection and sensing due to their rapid response time, high sensitivity, wide dynamic range, high specificity, label-free detection, portability, and cost-effectiveness. FET-based biosensors can be modified with specific recognition elements, thus providing real-time qualitative and semiquantitative analysis. Furthermore, with advances in nanotechnology and device design, various high-performance nanomaterials are gradually applied in the detection of FET-based biosensors. In this article, we review specific detection in different biological recognition elements are immobilized on FET biosensors for the detection of pathogenic microorganisms and toxins, and we also discuss nonspecific detection by FET biosensors. In addition, there are still unresolved challenges in the development and application of FET biosensors for achieving efficient, multiplexed, in situ detection of pathogenic microorganisms and toxins. Therefore, directions for future FET biosensor research and applications are discussed.

Density functional theory studies of Ti3C2TxMXene nanosheets decorated with Au for sensing SF6/N2nitrogen-containing decomposition gases.

SF6/N2mixture is an alternative gas of SF6, which is already used in electrical equipment. When a malfunction occurs , SF6/N2will decompose and further react with trace water and oxygen to produce nitrogen-containing gases such as NO, NO2, N2O and NF3. It is necessary to monitor these gases to ensure the safe operation of the equipment. This paper is based on density functional theory (DFT), the nanomaterial Ti3C2Txdoped with Au atom was selected as sensing material. The result shows that Au/Ti3C2Txhas larger adsorption energy when NO and NO2adsorbed on the surface, the stable structures were conformed more easily with NO and NO2compared with N2O and NF3. The density of states analysis and the frontier molecule orbital analysis reveal more change of the system before and after NO and NO2adsorption, suggesting the material showed good sensitivity performance to NO and NO2. Thus, Au/Ti3C2Txis considered to have the potential for sensing NO and NO2.

Association of adiposity indices with cardiometabolic multimorbidity among 101,973 chinese adults: a cross-sectional study.

BACKGROUND: Cardiometabolic multimorbidity (CMM) and obesity represent two major health problems. The relationship between adiposity indices and CMM, however, remains understudied. This study aimed to investigate the associations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and conicity index (CI) with CMM among Chinese adults. METHODS: Data of 101,973 participants were collected from a population-based screening project in Southern China. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, hypertension, and diabetes. The relationship between the six adiposity indices and CMM was investigated by multivariate logistic regression and restricted cubic splines. Receiver operator characteristic curve, C-statistic and net reclassification index were used to estimate the discriminative and incremental values of adiposity indices on CMM. RESULTS: Logistic regression models showed the six adiposity indices were all significantly associated with the odds of CMM with non-linear relationships. For per SD increment, WC (Odds ratio [OR]: 1.66; 95% confidence interval (CI): 1.62-1.70) and WHtR (OR, 1.61; 95% CI, 1.58-1.65) were more significantly associated with a higher prevalence of CMM than BMI (OR, 1.55; 95% CI, 1.52-1.58) (all P < 0.05). In addition, WC, WHtR, and BRI displayed significantly better performance in detecting CMM compared with BMI (all P < 0.05). Their respective area under the curve (AUC) values were 0.675 (95% CI: 0.670-0.680), 0.679 (95% CI: 0.675-0.684), and 0.679 (95% CI: 0.675-0.684), while BMI yielded an AUC of 0.637 (95% CI: 0.632-0.643). These findings hold true across all subgroups based on sex and age. When Adding WC, WHtR, or BRI to a base model, they all provided larger incremental values for the discrimination of CMM compared with BMI (all P < 0.05). CONCLUSIONS: Adiposity indices were closely associated with the odds of CMM, with WC and WHtR demonstrating stronger associations than BMI. WC, WHtR, and BRI were superior to BMI in discriminative ability for CMM. Avoidance of obesity (especially abdominal obesity) may be the preferred primary prevention strategy for CMM while controlling for other major CMM risk factors.

Drought Eliminates the Difference in Root Trait Plasticity and Mycorrhizal Responsiveness of Two Semiarid Grassland Species with Contrasting Root System.

Root traits and arbuscular mycorrhizal (AM) fungi are important in determining the access of plants to soil resources. However, whether plants with different root systems (i.e., taproot vs. fibrous-root) exhibit different root trait plasticity and mycorrhizal responsiveness under drought remains largely unexplored. Tap-rooted Lespedeza davurica and fibrous-rooted Stipa bungeana were grown in monocultures in sterilized and live soils, followed by a drought treatment. Biomass, root traits, root colonization by AM fungi, and nutrient availability were evaluated. Drought decreased biomass and root diameter but increased the root:shoot ratio (RSR), specific root length (SRL), soil NO3--N, and available P for the two species. Under control and drought conditions, soil sterilization significantly increased the RSR, SRL, and soil NO3--N for L. davurica, but this only occurs under drought condition for S. bungeana. Soil sterilization significantly reduced AM fungal root colonization of both species, but drought significantly increased it in live soil. In water-abundant conditions, tap-rooted L. davurica may depend more on AM fungi than fibrous-rooted S. bungeana; however, under drought conditions, AM fungi are of equal importance in favoring both plant species to forage soil resources. These findings provide new insights for understanding the resource utilization strategies under climate change.

Soy isoflavone-specific biotransformation product S-equol in the colon: physiological functions, transformation mechanisms, and metabolic regulatory pathways.

Epidemiological data suggest that regular intake of soy isoflavones may reduce the incidence of estrogen-dependent and aging-associated disorders. Equol is a metabolite of soy isoflavone (SI) produced by specific gut microbiota and has many beneficial effects on human health due to its higher biological activity compared to SI. However, only 1/3 to 1/2 of humans are able to produce equol in the body, which means that not many people can fully benefit from SI. This review summarizes the recent advances in equol research, focusing on the chemical properties, physiological functions, conversion mechanisms in vitro and vivo, and metabolic regulatory pathways affecting S-equol production. Advanced experimental designs and possible techniques in future research plan are also fully discussed. Furthermore, this review provides a fundamental basis for researchers in the field to understand individual differences in S-equol production, the efficiency of metabolic conversion of S-equol, and fermentation production of S-equol in vitro.

Prevalence and prognosis of left ventricular diastolic dysfunction in community hypertension patients.

Left ventricular diastolic dysfunction (LVDD) is common in hypertension and is a predictor of increased cardiovascular risk, however the effect of LVDD, detected by new guideline, on major adverse cardiac events (MACE) is unknown in hypertensive patients without known cardiovascular disease. The present study aims to evaluate LVDD in a community hypertension cohort study and assess the effect of LVDD on MACE. we studied 283 asymptomatic nonischemic patients with hypertension who had baseline echocardiogram between 2012 and 2014. Patients were followed for MACE (myocardial infarction, coronary revascularization procedures, heart failure, stroke, all-cause mortality) with mean follow-up of 5.4 years. A Cox proportional hazards model was used to assess the association of LVDD with MACE. At baseline, 35 of the 283 hypertensions were diagnosed with LVDD (12.3%) and 25 patients were women (15.5%). Women had higher frequency of LVDD than men (8%). During follow-up, there were 26.6% patients occurring MACE in the LVDD group at baseline, 9.9% patients occurring MACE in the group with normal diastolic function. In multivariable Cox regression analyses, LVDD was a stronger predictor of MACE (HR: 2.5; 95% CI: 1.20 to 5.25; c- statistics 0.805) than E/e' ratio (HR: 1.13; 95% CI: 1.04 to 1.22). LVDD was strongly associated with MACE in hypertension patients.

[Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics].

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-ß1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-ß1-stimulated NRK-52 E cells were treated with or without 5 µmol·L~(-1) ICA+10 µmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-ß1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-ß1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

One-Step Template/Solvent-Free Pyrolysis for In Situ Immobilization of CoP Nanoparticles onto N and P Co-Doped Carbon Porous Nanosheets towards High-efficiency Electrocatalytic Hydrogen Evolution.

The search for economical, active and stable electrocatalysts towards the hydrogen evolution reaction (HER) is highly imperative for the progression of water electrolysis technology and related sustainable energy conversion technologies. The delicate optimization of chemical composition and architectural configuration is paramount to design high-efficiency non-precious metal HER electrocatalysts. Herein, we report a one-step scalable template/solvent-free pyrolysis approach for in situ immobilizing uniform CoP nanoparticles onto N and P co-doped carbon porous nanosheets (denoted as CoP@N,P-CNSs hereafter). The simultaneous consideration of architectural design and nanocarbon hybridization renders the formed CoP@N,P-CNSs with plentiful well-dispersed anchored active sites, shortened pathway for mass diffusion, enhanced electric conductivity, and reinforced mechanical stability. As a consequence, the optimized CoP@N,P-CNSs exhibit an overpotential of 115 mV to afford a current density of 10 mA cm-2 , small Tafel slope of 74.2 mV dec-1 , high Faradaic efficiency of nearly 100 %, and superb long-term durability in an alkaline medium. Given the fabrication feasibility, mass production potential and outstanding HER performance, the CoP@N,P-CNSs may hold great promise for large-scale electrochemical water splitting. More importantly, the explored one-step template/solvent-free pyrolysis methodology offers a feasible and versatile route to fabricate carbon nanosheet-based nanocomposites for diverse energy conversation-related applications.

Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1ß/transforming growth factor-ß-mediated activation of renal fibroblasts.

Icariin (ICA) is a bioactive flavonoid extracted from Epimedium brevicornum Maxim and exhibits a variety of pharmacological activities including antiinflammatory and antioxidant effects. Recently, icariin has shown renoprotective role by inhibiting pathological matrix. However, the underlying mechanisms of the efficacy remain unknown. This study aimed to determine the effects of icariin on renal fibrosis and explore its molecular mechanisms. Chronic kidney disease (CKD) was induced in rats with 5/6 ablation and infarction (A/I) operation. Four weeks later, rats were treated with vehicle or 20 mg/kg (low dose) or 40 mg/kg (high dose) of icariin by daily gavage. Furthermore, to further elucidate the effect mechanisms of icariin, in vitro, NRK-49F cells stimulated by 8 ng/ml IL-1ß were treated with icariin in the presence or absence of SB431542 or the neutralizing antibody of transforming growth factor-ß (TGF-ß) for 24 h. We showed that icariin treatment for 8 weeks dose-dependently improved 5/6 (A/I)-induced kidney injury and fibrosis, and blocked the release of inflammatory cytokine IL-1ß. In vitro, icariin inhibited IL-1ß/TGF-ß-mediated activation of renal fibroblasts. In summary, anti-fibrotic effects of icariin were interconnected with the inhibition of renal fibroblast activation caused by IL-1ß/TGF-ß signaling.

Effects of intensive blood-pressure treatment on myocardial work in elderly hypertensive patients: A subcenter study of the STEP randomized controlled trial.

BACKGROUND: The benefits and safety of intensive blood pressure treatment in elderly hypertensive patients have been proved in the STEP trial. However, relevant mechanisms for intensive treatment are lacking. HYPOTHESIS: We aimed to explore whether intensive blood pressure treatment is associated with left ventricular systolic function changes as evaluated by myocardial work (MW) parameters in elderly hypertensive patients compared to the standard. METHODS: Patients were randomized to the intensive group (n = 66, median age 66 years, 42.4% male) with a systolic blood pressure (SBP) goal of 110 to <130 mmHg or the standard treatment group (n = 50, median age 63.5 years, 30% male) with an SBP goal of 130-<150 mmHg in this subcenter study of the STEP trial. There was no pre-randomization echocardiographic collected. Echocardiographic exam was produced at 1-year (phase 1) and 3-year (phase 2) post-randomization. RESULTS: In phase 1, SBP was already significantly lower in the intensive treatment group than in the standard treatment group (126.5 vs. 132.1 mmHg, p < .05). During a median follow-up of 40 months, in phase 2, the intensive group still had a lower SBP than the standard treatment group (125.0 vs. 135.3 mmHg, p < .05). Both global work index (GWI) and global constructive work (GCW) decreased significantly in phase in the intensive treatment group but not in the standard group (p < .05). Global wasted work (GWW) increased and global work efficiency (GWE) declined in both groups from phase 1 to phase 2 while no significant difference between the treatment effects. Similarly, left ventricular ejection function (LVEF) and global longitudinal strain (GLS) decreased in the two groups. The multivariate linear regression analysis showed the intensive treatment appeared to be an independent predictor of the ΔGWI (ß = -110.92; 95% CI, -197.78 to -30.07, p = .008) and ΔGCW (ß = -135.11; 95% CI, -220.33 to -49.88, p = .002). CONCLUSIONS: In elderly hypertensive patients, lower SBP was associated with decreased GWI and GCW and intensive BP treatment did not improve global MW efficiency.

Ultra-sensitive and rapid detection of Salmonella enterica and Staphylococcus aureus to single-cell level by aptamer-functionalized carbon nanotube field-effect transistor biosensors.

Foodborne diseases caused by Salmonella enterica (S. enterica) and Staphylococcus aureus (S. aureus) significantly impact public health, underscoring the imperative for highly sensitive, rapid, and accurate detection technologies to ensure food safety and prevent human diseases. Nanomaterials hold great promise in the development of high-sensitivity transistor biosensors. In this work, field-effect transistor (FET) comprising high-purity carbon nanotubes (CNTs) were fabricated and modified with corresponding nucleic acid aptamers for the high-affinity and selective capture of S. enterica and S. aureus. The aptamer-functionalized CNT-FET biosensor demonstrated ultra-sensitive and rapid detection of these foodborne pathogens. Experimental results indicated that the biosensor could detect S. enterica at a limit of detection (LOD) as low as 1 CFU in PBS buffer, and S. aureus at an LOD of 1.2 CFUs, achieving single-cell level detection accuracy with exceptional specificity. The biosensor exhibited a rapid response time, completing single detections within 200 s. Even in the presence of interference from six complex food matrices, the biosensor maintained its ultra-sensitive (3.1 CFUs) and rapid response (within 200 s) characteristics for both pathogens. The developed aptamer-functionalized CNT-FET biosensor demonstrates a capability for low-cost, ultra-sensitive, label-free, and rapid detection of low-abundance S. enterica and S. aureus in both buffer solutions and complex environments. This innovation holds significant potential for applying this detection technology to on-site rapid testing scenarios, offering a promising solution to the pressing need for efficient and reliable pathogen monitoring in various settings.

Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise-induced fatigue via upregulating the glutaminemediated Ca2+ /Calcineurin signaling pathway in mice.

Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched-chain amino acids have anti-fatigue properties. However, the function of the sea cucumber intestine in reducing exercise-induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise-induced fatigue using swimming and pole-climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight-loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow-twitch muscle fiber and a significant decrease the proportion of fast-twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.

Shen Shuai II Recipe inhibits hypoxia-induced glycolysis by preserving mitochondrial dynamics to attenuate kidney fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen Shuai II Recipe (SSR) is a traditional Chinese medicine prescription with significant clinical efficacy in chronic kidney disease (CKD) by invigorating Qi and resolving blood stasis, clearing away heat and dampness. Our previous studies demonstrated that SSR attenuated renal interstitial fibrosis (RIF) by improving hypoxia and mitochondrial dysfunction. AIM OF THE STUDY: The aim of this study was to investigate the potential mechanisms of SSR against RIF. MATERIALS AND METHODS: The CKD was established by 5/6 ablation/infarction (A/I) operation. After 4 weeks, rats were gavaged with SSR or Fenofibrate for 8 weeks. Hypoxia-treated NRK-52 E cells were treated with SSR and (or) glycolysis inhibitors, including GSK2837808 A (GSK) and 2-Deoxy-D-glucose (2-DG). In addition, Drp1-deficient or MFP-M1-treated NRK-52 E cells were treated with SSR under hypoxic conditions. The effects of SSR on fibrotic phenotype, glycolysis, mitochondrial dynamics and membrane potential in hypoxia-exposed NRK-52 E cells were examined by immunoblotting, colorimetric, and fluorometric methods. Furthermore, we constructed a lactic acid-induced activation model of NRK-49 F cells and a co-culture system. The activation of NRK-49 F cells was evaluated by immunoblotting method. RESULTS: Our findings indicated that SSR significantly attenuated abnormal glycolysis in vivo and in vitro, which was correlated with its renoprotective effect. Further studies revealed that improvement of mitochondrial dynamics could be one of the mechanisms by which SSR inhibits glycolysis to achieve anti-renal fibrosis. Furthermore, treatment with SSR significantly inhibited the lactic acid-induced activation of NRK-49 F cells. The co-culture results further highlighted that SSR inhibited activation of renal fibroblasts and deposition of extracellular matrix by reducing glycolysis in renal tubular cells. CONCLUSIONS: SSR alleviates RIF by inhibiting hypoxia-induced glycolysis through improvement of mitochondrial dynamics.

Modeling Cardinality in Image Hashing.

Cardinality constraint, namely, constraining the number of nonzero outputs of models, has been widely used in structural learning. It can be used for modeling the dependencies between multidimensional labels. In hashing, the final outputs are also binary codes, which are similar to multidimensional labels. It has been validated that estimating how many 1's in a multidimensional label vector is easier than directly predicting which elements are 1 and estimating cardinality as a prior step will improve the classification performance. Hence, in this article, we incorporate cardinality constraint into the unsupervised image hashing problem. The proposed model is divided into two steps: 1) estimating the cardinalities of hashing codes and 2) then estimating which bits are 1. Unlike multidimensional labels that are known and fixed in the training phase, the hashing codes are generally learned through an iterative method and, therefore, their cardinalities are unknown and not fixed during the learning procedure. We use a neural network as a cardinality predictor and its parameters are jointly learned with the hashing code generator, which is an autoencoder in our model. The experiments demonstrate the efficiency of our proposed method.

Sex-specific risk factors of carotid atherosclerosis progression in a high-risk population of cardiovascular disease.

BACKGROUND: The progression of carotid intima-media thickness (cIMT) and plaques are associated with cardiovascular health, especially for high-risk population of cardiovascular disease (CVD). HYPOTHESIS: Risk factors for atherosclerosis may vary by sex. This study aimed to investigate the sex-specific risk factors of cIMT and plaque progression. METHODS: We selected subjects who were identified as high-risk population of CVD, and collected their carotid ultrasound data and baseline characteristics. Linear regression and logistic regression analyses were used to identify risk factors for cIMT and plaque progression. Sex-specific risk factors were identified respectively. RESULTS: A total of 7908 participants were included. The mean age was 57.75 ± 9.45 years and 61.51% were female. During mean follow-up of 1.92 ± 0.89 years, the median annual cIMT change rate was -7.25 µm/year. Seven hundred and fifteen subjects free from plaques at baseline developed plaque. Age, smoking, hypertension, and diabetes were common risk factors for carotid atherosclerosis progression in all participants. Smoking and alcohol drinking were significantly associated with increased cIMT change in women, while hypertension and antihypertensive medication were significant in men. Increased total cholesterol and diabetes were significantly associated with new plaque presence in women, while smoking, increased triglyceride, and dyslipidemia were significant in men (p ˂ .05 for all cases). The association of baseline cIMT and smoking with annual cIMT change rate and increased total cholesterol with new plaque presence were significantly differentiated between both sexes (p for interaction ˂ .05). CONCLUSIONS: The risk factors for cIMT and plaque progression differed by sex.

Longitudinal Study of Left Ventricular Mass Index Trajectories and Risk of Mortality in Hypertension: A Cohort Study.

Background Left ventricular mass index (LVMI) has been extensively studied for its relationship with mortality but has been typically assessed at a single time point. We, therefore, describe the trajectory of LVMI in a population with hypertension over 6 years to study the subsequent risk of mortality. Methods and Results We assessed LVMI that was collected during annual health examinations in round 1 (2010-2012), round 2 (2013-2014), and round 3 (2015-2016) with 2 allometric scalings, height2.7, and body surface area, in a cohort of participants with hypertension to identify 6-year trajectories of LVMI by latent class trajectory modeling. We followed up with participants for mortality by latent trajectory from the last echocardiographic examination (September 17, 2014-December 8, 2016) to December 31, 2018. We calculated mortality hazard ratios by assigned trajectory using Cox proportional hazards models. We obtained data for LVMI from 2453 participants (mean age, 61.80 [SD, 12.14] years, 1428 [58.2%] female). We identified 3 trajectories of LVM/H2.7, characterized by maintained low stable (1298 [52.9%]); moderate stable (935 [38.1%]); high stable (220 [9.0%]), as well as 3 trajectories by LVM/body surface area. During a median follow-up of 2.15 years, 167 participants developed all-cause mortality, and 71 were cardiovascular mortality. Only the high stable trajectory was associated with a higher risk of all-cause mortality compared with the low stable trajectory by LVM/H2.7 or LVM/body surface area (all P<0.05). In Kaplan-Meier survival analysis, the trajectory with high stable LVM/body surface area had significantly lower survival probability. Conclusions In community hypertension, the individuals with high stable LVMI trajectory had the highest risk of all-cause mortality. The individuals in the moderate stable trajectory had a similar risk for mortality as those in the low stable trajectory.

A micro-carbon nanotube transistor for ultra-sensitive, label-free, and rapid detection of Staphylococcal enterotoxin C in food.

Staphylococcal enterotoxin C (SEC) is an enterotoxin produced by Staphylococcus aureus, which can cause intestinal diseases. Therefore, it is of great significance to develop a sensitive detection method for SEC to ensure food safety and prevent foodborne diseases in humans. A field-effect transistor (FET) based on high-purity carbon nanotubes (CNTs) was used as a transducer, and a nucleic acid aptamer with high affinity was used for recognition to capture the target. The results indicated that the biosensor achieved an ultra-low theoretical detection limit of 1.25 fg/mL in PBS, and its good specificity was verified by detecting target analogs. Three typical food homogenates were used as the solution to be measured to verify that the biosensor had a swift response time (within 5 min after sample addition). An additional study with a more significant basa fish sample response also showed excellent sensitivity (theoretical detection limit of 8.15 fg/mL) and a stable detection ratio. In summary, this CNT-FET biosensor enabled the label-free, ultra-sensitive, and fast detection of SEC in complex samples. The FET biosensors could be further used as a universal biosensor platform for the ultrasensitive detection of multiple biological toxic pollutants, thus considerably stopping the spread of harmful substances.

Azithromycin Exposure Induces Transient Microbial Composition Shifts and Decreases the Airway Microbiota Resilience from Outdoor PM2.5 Stress in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled Trial.

Inappropriate antibiotic prescriptions are common for patients with upper respiratory tract infections (URTIs). Few data exist regarding the effects of antibiotic administration on airway microbiota among healthy adults. We conducted a randomized, double-blind, placebo-controlled trial to characterize the airway microbiota longitudinally in healthy adults using 16S rRNA gene sequencing and quantification. Both the induced sputum and oral wash samples were collected over a 60-day period following a 3-day intervention with 500 mg azithromycin or placebo. Environmental information, including air quality data (particulate matter [PM2.5] and PM10, air quality index [AQI] values), were also collected during the study. A total of 48 healthy volunteers were enrolled and randomly assigned into two groups. Azithromycin did not alter bacterial load but significantly reduced species richness and Shannon index. Azithromycin exposure resulted in a decrease in the detection rate and relative abundance of different genera belonging to Veillonellaceae, Leptotrichia, Fusobacterium, Neisseria, and Haemophilus. In contrast, the relative abundance of taxa belonging to Streptococcus increased immediately after azithromycin intervention. The shifts in the diversity of the microbiology composition took between 14 and 60 days to recover, depending on the measure used: either UniFrac phylogenetic distance or α-diversity. Outdoor environmental perturbations, especially the high concentration of PM2.5, contributed to novel variability in microbial community composition of the azithromycin group at D30 (30 days after baseline). The network analysis found that azithromycin altered the microbial interactions within airway microbiota. The influence was still obvious at D14 when the relative abundance of most taxa had returned to the baseline level. Compared to the sputum microbiota, oral cavity microbiota had a different pattern of change over time. The induced sputum microbial data can represent the airway microbiota composition in healthy adults. Azithromycin may have transient effects in the airway microbiota of healthy adults and decrease the airway microbiota resilience against outdoor environmental stress. The influence of azithromycin on microbial interactions is noteworthy, although the airway microbiota has returned to a near-baseline level. IMPORTANCE The influence of antibiotic administration on the airway microbiota of healthy adults remains unknown. This study is a randomized, double-blind, placebo-controlled trial aiming to investigate the microbial shifts in airways after exposure to azithromycin among heathy adults. We find that azithromycin changes the airway microbial community composition of healthy adults and decreases the airway microbiota resilience against outdoor environmental stress. This study depicts the longitudinal recovery trajectory of airway microbiota after the antibiotic perturbation and may provide reference for appropriate antibiotic prescription.