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Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg

AbstractBackground Sarcopenia is a common complication of liver cirrhosis and can be used for predicting dismal prognostic outcomes. This study aimed to evaluate the role of sarcopenia in rebleeding and mortality of liver cirrhosis patients after endoscopic therapy.Methods The liver cirrhosis patients who received endoscopic treatment were enrolled. Propensity score matching (PSM) was used to overcome selection bias. Two-year rebleeding episodes and mortality after endoscopic therapy were recorded.Results A total of 109 (32.4%) sarcopenia patients were reported. Before PSM, the frequency of rebleeding was significantly higher in the sarcopenia group relative to the non-sarcopenia group (41.3% vs. 15.9%, p

Tobacco is a special commercial crop that prefers potassium but not chlorine, and excessive chloride (Cl–) accumulation can cause toxicity. Here, we revealed that the structural characteristics of chloroplasts in tobacco leaves were significantly destroyed under high Cl– salinity, but not mitochondria. Large differences in leaf structure, MDA content, and antioxidant enzyme activities were observed for the treatment with highest chloride accumulation at the 14th day. Moreover, RNA-seq analysis of tobacco leaves exposed to high Cl– salinity revealed global changes in gene transcription levels. A total of 1360 DEGs involved in cell wall, lipid, starch, and secondary metabolism processes were unevenly distributed on chromosomes, and were mainly enriched for starch and sucrose metabolism, phenylpropanoid biosynthesis, ribosome and ribosome biogenesis, protein processing in the endoplasmic reticulum, and plant hormone signal transduction pathways. Overall, our study provides valuable insights for further research on the mechanism underlying Cl– salinity and salt-tolerant tobacco development.

The urban logistics delivery planning problems are a crucial component of urban spatial decision analysis. Most studies typically focus on traditional urban logistics delivery planning problems and ignore real-time traffic information. With the advancement of urbanization, real-time traffic networks play a critical role. However, previous studies have utilized heuristic methods to solve urban logistics delivery planning with real-time traffic information problems, and few studies have applied deep reinforcement learning methods to tackle this problem. Deep reinforcement learning methods solving traditional logistics delivery planning problems overlook the impact of dynamic spatio-temporal features on route planning. In this study, we propose a new deep reinforcement method called DRLDSTG. The method introduces the dynamic spatio-temporal graph model into a deep reinforcement learning method to capture these dynamic features from urban logistics delivery planning tasks. The actor-critic with maximum entropy method is employed to train the model and determine the optimal policy function. The experimental results indicated that the proposed method can achieve a superior solution with faster computational efficiency compared to commercial software and heuristic methods. Compared to other deep reinforcement learning methods, our method can more effectively learn dynamic spatio-temporal features from environments, demonstrating promising applications in cities.

Doxorubicin (DOX)-mediated cardiotoxicity can impair the clinical efficacy of chemotherapy, leading to heart failure (HF). Given the importance of circRNAs and miRNAs in HF, this paper intended to delineate the mechanism of the circular RNA 0006332 (circ -0,006,332)/microRNA (miR)-143/Toll-like receptor 2 (TLR2) axis in doxorubicin (DOX)-induced HF. The binding of miR-143 to circ -0,006,332 and TLR2 was assessed with the dual-luciferase assay, and the binding between miR-143 and circ -0,006,332 was determined with FISH, RIP, and RNA pull-down assays. miR-143 and/or circ -0,006,332 were overexpressed in rats and cardiomyocytes, followed by DOX treatment. In cardiomyocytes, miR-143 and TLR2 expression, cell viability, LDH release, ATP contents, and levels of IL-1β, IL-18, TNF-α, and pyroptosis-related molecules were examined. In rats, cardiac function, serum levels of cardiac enzymes, apoptosis, myocardial fibrosis, and levels of IL-1β, IL-18, TNF-α, TLR2, and pyroptosis-related molecules were detected. miR-143 diminished TLR2 expression by binding to TLR2, and circ -0,006,332 bound to miR-143 to downregulate miR-143 expression. miR-143 expression was reduced and TLR2 expression was augmented in DOX-induced cardiomyocytes. miR-143 inhibited DOX-induced cytotoxicity by suppressing pyroptosis in H9C2 cardiomyocytes. In DOX-induced rats, miR-143 reduced cardiac dysfunction, myocardial apoptosis, myocardial fibrosis, TLR2 levels, and pyroptosis. Furthermore, overexpression of circ -0,006,332 blocked these effects of miR-143 on DOX-induced cardiomyocytes and rats. Circ -0,006,332 stimulates cardiomyocyte pyroptosis by downregulating miR-143 and upregulating TLR2, thus promoting DOX-induced cardiac injury.

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.

The daily operations of large hydropower stations on rivers induce frequent variations in downstream water levels and flow velocities, resulting in unsteady and complex hydraulic characteristics at the confluence of the main stream and its tributaries, which adversely affect navigation safety. The continuity and momentum equations, along with the RNG k-ϵ turbulence model and the VOF model, were employed to simulate the river flow process at the confluence under unsteady flow conditions. The simulated results for water levels and velocity vector fields are in good agreement with experimental data. Variations in hydraulic characteristics, including water level, flow velocity, and longitudinal gradient at the confluence of the main stream and its tributaries, were analysed. The results indicated that the water level at the confluence decreases when the tributary merges with the main stream. As the confluence ratio increases, fluctuations in the water level at the confluence decrease. However, an increase in the staggered period results in greater fluctuations in the water level within this region. Moreover, a crescent-shaped high-speed flow region is formed at the confluence of the tributary and the main stream. As the unsteady flow discharge of the main stream increases, the relative area of this region correspondingly enlarges, reaching its maximum at peak discharge, and subsequently gradually diminishes as the discharge decreases. Based on these simulation data, a Long Short-Term Memory (LSTM) model was developed to effectively predict water levels and flow velocities, providing a more convenient and accurate method for obtaining real-time information on confluence areas than traditional mathematical and statistical approaches. This study provides novel insights into predicting flow characteristics in confluence areas, thereby offering a basis for formulating navigation safety plans.

Persistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p

ABSTRACTSopF, a newly discovered effector secreted by Salmonella pathogenicity island-1 type III secretion system (T3SS1), was reported to target phosphoinositide on host cell membrane and aggravate systemic infection, while its functional relevance and underlying mechanisms have yet to be elucidated. PANoptosis (pyroptosis, apoptosis, and necroptosis) of intestinal epithelial cells (IECs) has been characterized as a pivotal host defense to limit the dissemination of foodborne pathogens, whereas the effect of SopF on IECs PANoptosis induced by Salmonella is rather limited. Here, we show that SopF can attenuate intestinal inflammation and suppress IECs expulsion to promote bacterial dissemination in mice infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). We revealed that SopF could activate phosphoinositide-dependent protein kinase-1 (PDK1) to phosphorylate p90 ribosomal S6 kinase (RSK) which down-regulated Caspase-8 activation. Caspase-8 inactivated by SopF resulted in inhibition of pyroptosis and apoptosis, but promotion of necroptosis. The administration of both AR-12 (PDK1 inhibitor) and BI-D1870 (RSK inhibitor) potentially overcame Caspase-8 blockade and subverted PANoptosis challenged by SopF. Collectively, these findings demonstrate that this virulence strategy elicited by SopF aggregates systemic infection via modulating IEC PANoptosis through PDK1-RSK signaling, which throws light on novel functions of bacterial effectors, as well as a mechanism employed by pathogens to counteract host immune defense.

Background: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it’s urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. Method: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. Results: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual’s humoral responses against the latest Omicron subvariants. Conclusions: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Background/Aim Uremic cardiomyopathy (UCM) is a characteristic cardiac pathology that is commonly found in patients with chronic kidney disease. This study dissected the mechanism of SPI1 in myocardial fibrosis and inflammation induced by UCM through S100A8/A9.Methods An UCM rat model was established, followed by qRT-PCR and western blot analyses of SPI1 and S100A8/A9 expression in myocardial tissues. After alterations of SPI1 and S100A8/A9 expression in UCM rats, the blood specimens were harvested from the cardiac apex of rats. The levels of creatine phosphokinase-MB (CK-MB), blood creatinine, blood urea nitrogen (BUN), and inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor-α [TNF-α]) were examined in the collected blood. Collagen fibrosis was assessed by Masson staining. The expression of fibrosis markers [transforming growth factor (TGF)-β1, α-smooth muscle actin (SMA), Collagen 4a1, and Fibronectin], IL-6, IL-1β, and TNF-α was measured in myocardial tissues. Chromatin immunoprecipitation and dual-luciferase reporter gene assays were conducted to test the binding relationship between SPI1 and S100A8/A9.Results S100A8/A9 and SPI1 were highly expressed in the myocardial tissues of UCM rats. Mechanistically, SPI1 bound to the promoter of S100A8/A9 to facilitate S100A8/A9 transcription. S100A8/A9 or SPI1 knockdown reduced myocardial fibrosis and inflammation and the levels of CK-MB, blood creatinine, and BUN, as well as the expression of TGF-β1, α-SMA, Collagen 4a1, Fibronectin, IL-6, TNF-α, and IL-1β in UCM rats.Conclusion SPI1 knockdown diminished S100A8/A9 transcription, thus suppressing myocardial fibrosis and inflammation caused by UCM.

The Global Ecosystem Dynamics Investigation (GEDI), a new spaceborne LiDAR system of the National Aeronautics and Space Administration (NASA), has the potential to revolutionize global measurements of vertical vegetation structure. However, GEDI performance among different forest types and factors influencing GEDI performance needs to be evaluated against similar measurements from existing airborne LiDAR platforms. Ideally, comparisons across diverse forest types will inform future work quantifying biomass or mapping species habitats. Thus, we compared the second version of GEDI L2A product (GEDI V2) with Airborne Observation Platform (AOP) leaf-on LiDAR data across 33 National Ecological Observation Network (NEON) sites. Comparisons were made for ground elevation and relative height (RH) of GEDI with simulated airborne laser scanning (ALS) waveforms from discrete point cloud LiDAR. Results indicated that GEDI V2 obtained high accuracy on ground elevation and RH100 estimations (3σ) with RMSEs of 1.38 m and 2.62 m, respectively. GEDI produced forest height estimations (RH100) for all 12 forest types with a %RMSE below 25%. GEDI RHs were sensitive to ground finding accuracy, and GEDI performance of RH estimation varied from forest profiles of different forest types. For factors influencing GEDI performance, greater than 21% of GEDI RH95 and 33% of ground elevation variations can be explained by land surface attributes, observing sensor system characteristics, and the collection time differences between GEDI and NEON LiDAR. Furthermore, geolocation error remains an essential factor affecting GEDI performance, which varies among forest and land cover types, especially for canopy height estimation. The findings reported here can provide insights to guide and enhance future GEDI-based global forest structure mapping and applications.

The wetting property to different oil of cotton fibers which come from different regions of China was studied. The surface adsorption characteristics of cotton fibers were characterized. It is found that the oleophilic and hydrophobic properties of all the raw cotton fibers are fantastic and the average static contact angle of cotton fibers to water is 135.36°, but it is less than 51° to different oil such as engine oil, waste oil and salad oil. In the dynamic spreading process, the droplets of water formed on the surface of cotton fibers and the contact angles of all the cotton fibers to water is not changing with time while the oil liquids were quickly and completely spread out almost in 2000 ms. The speed of spreading is closely relevant with the viscosity of oil and the higher oil viscosity, the slower wetting velocity. The contact angles of cotton fibers come from different regions to the same oil liquid had little changes, thus the adsorption velocity difference of cotton fibers to engine oil, waste oil and salad oil was not significant, respectively.

AbstractEnvironmental DNA (eDNA) metabarcoding permits a new measurement to monitor biodiversity in aquatic ecosystems. This study utilized eDNA metabarcoding to examine the seasonal and spatial distribution of phytoplankton and their relationship with environmental factors in the Chai River, Kunming, China, in the dry, and wet seasons. The process detected 108 genera of phytoplankton, which were members of 11 phyla, 41 orders, and 60 families. Distinct differences in seasonal and spatial distribution patterns of phytoplankton diversity, including community structure, α-diversity, and representative functional groups, were observed. In the dry season, Pseudanabaena, Microcystis, and Synechococcus were the predominant genera in Cyanophyta, and Chlorophyta, Bacillariophyta and Euglenophyta were predominant in the eukaryotic phytoplankton. While in the wet season, Cylindrospermopsis, Microcystis, and Planktothrix predominated in the Cyanophyta, and Bacillariophyta, Chlorophyta and Xanthophyta predominated in the eukaryotic phytoplankton. Significant differences were shown by a principal coordinate analysis and PERMANOVA test among the upper, middle, and lower reaches of the phytoplankton communities except for the cyanobacterial community structure between the upper and lower reaches at the wet season (p > 0.05). The representative functional groups of phytoplankton varied from A, D, E, LM, L0, N, S1, MP, P, TB, TC, U, W0, W1, Xph, Y, and Z in the dry season to A, B, D, E, F, J, MP, LM, S1, SN, TC, P, W0, W1, X2, and Y in the wet season. Significant differences in the water temperature (WT), pH, chemical oxygen demand, oxygen consumed, nitrate nitrogen (NO3-N), and chlorophyll a were exhibited between the dry and wet seasons (p

The jute/polylactic acid (PLA) composite material has been widely concerned in the field of composite materials because of its green, degradable and renewable properties, but its low mechanical properties limit the application field. In order to improve the mechanical properties of jute/PLA composites, styrene butadiene rubber (SBR) particles modified by different silane coupling agents were introduced into PLA matrix, and jute/PLA composites were prepared by solution casting and molding method. The changes in the mechanical properties of the jute/PLA composite were studied, and the toughening mechanism of the jute/PLA composite was analyzed. The results show that SBR particles can induce the crystallization of the PLA matrix, and the coupling agent plays a promoting role. The addition of SBR improves the bending and stretching of the jute/PLA composite. The silane coupling agent KH560 has the best modification effect on SBR particles. When the mass fraction of KH560-SBR particles in the composite is 1.0%, its bending strength and modulus achieve the highest, which are respectively 247.04% and 773.91% higher than the control group. When the mass fraction of KH560-SBR particles added in the composite is 2.0%, its tensile strength and modulus are the largest, 517.91% and 472.00% higher than the control group.

Objective This article is aimed to investigate the function and underlying action mechanism of Fisetin in LPS-induced PE rats. Methods LPS-induced PE-like rat model was established to explore the effects of Fisetin on PE in vivo. Results Fisetin reduced hypertension, proteinuria, TNF-α, IL-6, IL-1β, MDA, and sFlt-1/PlGF ratio, but elevated the placental, fetal weight, GSH and SOD in PE rats. Moreover, Fisetin suppressed TLR4/NF-κB pathway, as well as promoting Nrf2/HO-1 pathway in placental tissues of PE rats. Conclusions Fisetin exerted protective role and modulated the activation of TLR4/NF-κB and Nrf2/HO-1 pathways in PE-like rat models.

A fuzzy hierarchical comprehensive evaluation algorithm including fuzzy matrix and comprehensive evaluation matrix calculation thought is proposed to accurately evaluate the running state of an electromechanical system. The analytic hierarchy process is included in the algorithm, which calculates the state of each subsystem from top to bottom and the states are used as the evaluation factor of the upper system. The idea of degradation degrees is introduced to standardize the indicators. The paper carried out the simulation experiment for the electromechanical system with a model number of JKMD-4 × 4(Z). The experimental results show that the established state evaluation model can accurately judge the operation state of the system with not too much data.

Introduction: Young adults may be facing growing threats from vaccine-preventable diseases (VPDs). However, vaccination of young adults may not have drawn adequate attention. In Asia, adensely populated region with ahigh proportion of low-income countries, VPDs impose more of an economic and social burden than in western countries. However, knowledge about attitudes toward vaccines among young Asians is limited. This study aims to fill that gap by describing attitudes toward vaccines and how well they are accepted among young Asian adults through asystematic review of relevant Chinese and English publications. Methods: A three-stage searching strategy was adopted to identify eligible studies published during 2009–2019 according to the selection criteria, resulting in 68 articles being included. Results: The review finds that vaccination coverage among young Asians is generally lower than among their western peers, and there is a lack of relevant study in many Asian countries. Factors influencing young Asians’ attitudes toward vaccines are categorized into contextual level, individual and social level, and vaccine-specific level. Conclusion: These suggest that there is a need to strengthen young adults’ vaccination programs and to promote vaccine-related information and government.

Camellia rubituberculata Chang ex Lin et Lu is an endemic woody plant species with ornamental and edible oil value in Guizhou, China. Lack of genetic information seriously hinders its conservation and sustainable utilization. In this study, its complete chloroplast genome was assembled and annotated. Results show that the total length of the genome is 157,137 bp, in which the LSC is 86,782 bp in length, the SSC is 18,279 bp, and the length of the two long repeat regions is 26,038 bp, respectively. A total of 115 genes in the chloroplast genome of C. rubituberculata were annotated, including 80 protein-coding genes, 29 tRNA genes and 4 rRNA genes. In addition, there are 19 genes with two copies in the genome. Phylogenetic tree based on 62 homologous coding genes from 24 species chloroplast genomes showed that C. anlungensis is the most closely related species of C. rubituberculata. These results could enrich the chloroplast genomic information of Theaceae species, and lay a solid foundation for the study of phylogenetic relationships of this family, as well as the conservation and sustainable utilization of C. rubituberculata.

Radioactive levels and radiological hazard assessment associated with exposure to radionuclides from uranium tailings were investigated in this study. Herein, the concentrations of 238U, 226Ra, 232Th, and 40K in 36 samples including 25 soil and 11 water samples were measured using a low background HPGe semiconductor detector. The radionuclide concentrations were much lower outside the tailings reservoir than inside the reservoir; however, both exceeded the national average and world average values. The mean concentrations of 238U, 226Ra, 232Th, and 40K in water samples were higher than the WHO guideline levels. The radionuclide transfer factors showed that the radionuclides in soil of the tailings enter the surrounding water. Additionally, the radiological hazard indices around the reservoir were much higher than the worldwide average. Results suggest that the high level of radiation in the tailings reservoir posed a potential threat to the health of the local residents.

Puerarin (Pue) is the most abundant isoflavonoid in kudzu root. It has been widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, poor-bioavailability of puerarin is the main obstacle to its widespread clinical applications. In this paper, HA-ADH-PS nanomicelles were prepared by chemical modification, noncovalent modification and etc, and characterized by means of FT-IR, ultraviolet (UV) and thermogravimetric analysis (TG). The encapsulation efficiency and drug loading of Pue-loaded HA-ADH-PS nanomicelles were 45.1% and 19.89% by UV, respectively. It could be observed from the transmission electron microscopy (TEM) images that HA-ADH-PS micelles appeared obvious spherical structure in the water. The particle size of HA-ADH-PS nanomicelles and Pue-loaded HA-ADH-PS nanomicelles were about 136.8 nm and 119.5 nm with a PDI of 0.237 and 0.272, respectively. The fluorescence probe method was used to characterize the critical micelle concentration, the critical micelle concentration (CMC) value of the nanomicells was 0.002 g/L and the results met the requirements and ensured the stability of micelles after dilution. DPPH assay suggested that Pue-loaded HA-ADH-PS nanomicelles had an obvious radical scavenging effect in vitro. MTT test showed that Pue-loaded HA-ADH-PS nanomicelles was non-toxic and had good biocompatibility. Thus, Pue-loaded HA-ADH-PS nanomicelles could be used as a potential drug carrier for puerarin.

Staphylococci are the main cause of nosocomial infections globally. The exotoxin staphylococcal enterotoxin B (SEB) produced by methicillin-resistant Staphylococcus aureus is a major cause of pathology after a staphylococcal infection. We previously isolated an anti-SEB human monoclonal antibody designated as M0313. Here we further characterize this antibody in vitro and in vivo. Immunoblotting analysis and ELISA results indicated that M0313 accurately recognized and bound to SEB. Its binding affinity to native SEB was measured at the low nM level. M0313 effectively inhibited SEB from inducing mouse splenic lymphocyte and human peripheral blood mononuclear cell proliferation and cytokine release in cell culture. M0313 also neutralized SEB toxicity in BALB/c female mice. Most importantly, M0313 promoted the survival of mice treated with SEB-expressing bacteria. In-vivo imaging revealed that M0313 treatment significantly reduced the replication of SEB-expressing bacteria in mice. The neutralization capacity of M0313 correlated with its ability to block SEB from binding to major histocompatibility complex II and T-cell receptor by binding to the SEB residues 85–102 and 90–92. Thus, the monoclonal antibody M0313 may be developed into a therapeutic agent.

The “Zaoheibao” fruit with rich rose-scented grapes was used as the main material to optimize the fermentation process of “Zaoheibao” wine. Its composition in volatile aroma compounds was determined by headspace solid phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC–MS) analysis, indicating that “Zaoheibao” wine has strong ester, fruity and floral characteristics. The addition of 30 mg/L SO2 and 200 mg/L yeast, and a fermentation time of 6 days were indicated as the optimal fermentation conditions, where 35 volatile aroma substances were detected and a relative ester content of 45.59% was achieved. Among the identified ester compounds, isoamyl ester, ethyl octanoate, ethyl acetate, 2-methyltetrahydrothiophen-3-one, 4-hydroxy-2-butanone, linalool and 2,4-dimethyl-1-heptene contributed mainly to the aroma characteristics of “Zaoheibao” wine. The obtained results will allow the production of higher quality “Zaoheibao” wine and serve as a guide to improve the characteristics of other wine varieties.

During the Small Baseline Subsets (SBAS) InSAR processing, the interferograms are often separated into multiple independent subsets, which results inevitably in a rank deficiency problem. Singular value decomposition (SVD) or linear interpolation based least squares (LS) is generally adopted, which causes systematically biased deformation estimation. Therefore, we presents a constrained SBAS method, which takes the period of the time series deformation detected by frequency-spectrum analysis as constraints to solve the rank deficiency problem. This method is illustrated with simulated data in detail. The results of the SVD, LS and our methods are in agreement with the true value in the first subset, but biased in the second subset with the magnitudes of 17.39 cm, 15.90 cm and -0.53 cm, respectively, where our method is the best one. Lastly, the new method is successfully verified using the real SAR data over Southern California from 2003 to 2006. The averaged STD of the differences between our method and GPS observations in four stations are 5.0, 3.62, 6.31 and 5.87 mm/year, respectively, which is much better than those from SVD and LS methods. This outcome confirms the validity of the newly proposed method.

With the purpose of improving the water solubility and oral bioavailability, ursolic acid nanoparticles (UANs) were prepared by the emulsion solvent evaporation method, and the nanosuspension was freeze-dried into powder. The optimal conditions for preparing nanoparticles were screened out using single-factor experiment. Take advantage of the optimal conditions, UA nanoemulsion had mean particle size (MPS) of 69.7 ± 15.6 nm and polydispersity index value (PI) of 0.005. The MPS of UA nanosuspension was gained at 100.2 ± 12.1 nm (PI = 0.005), after the organic solvent was removed by rotary evaporator. Finally, UANs possessing an MPS of 157.5 ± 28.0 nm (PI = 0.005) and zeta potential of 20.33 ± 1.67 mV were obtained after freeze-dried. UANs were investigated using SEM, XRD, DSC, TGA and further explored their equilibrium solubility, dissolution rate, solvent residue analysis, cellular antioxidant activity and oral bioavailability. All the results above showed that UA in UANs was in the amorphous state. The result of solubility test figured that the equilibrium solubility of UANs was 13.48 times in simulated gastric fluid (SGF), 11.79 times in simulated intestinal fluid (SIF) and 23.99 times in deionized water than raw UA. Accordingly, the dissolution rate of UANs in SGF and SIF had an apparent enhancement. The oral bioavailability of UANs increased 2.68 times than raw UA. UANs improved antioxidant activity toward cells compared with raw UA, and EC50 of UANs reduced 37.5 times than raw UA. The residual contents of trichloromethane and ethanol were separated up to the mustard of the ICH limit for class III and class II solvents. The results above indicated that UANs possesses a value of application on enhancement oral bioavailability.

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease. In our previous investigations, we have reported the spectrum and frequency of mitochondrial MT-ND1, MT-ND4 and MT-ND6 gene in Chinese LHON population. This study aimed to assess the molecular epidemiology of MT-TT mutations in Chinese families with LHON. A cohort of 352 Chinese Han probands lacking the known LHON-associated mtDNA mutations and 376 control subjects underwent molecular analysis of mtDNA. All variants were evaluated for evolutionary conservation, structural and functional consequences. Fifteen variants were identified in the MT-TT gene by mitochondrial genome analysis of LHON pedigrees, which was substantially higher than that of individuals from general Chinese populations. The incidences of the two known LHON-associated mutations, m.15927G > A and m.15951A > G, were 2.27% and 1.14%, respectively. Nine putative LHON-associated variants were identified in 20 probands, translated into 2.1% cases of this cohort. Moreover, mtDNAs in 41 probands carrying the MT-TT mutation(s) were widely dispersed among nine Eastern Asian haplogroups. Our results suggest that the MT-TT gene is a mutational hotspot for these 352 Chinese families lacking the known LHON-associated mutations. These data further showed the molecular epidemiology of MT-TT mutations in Chinese Han LHON pedigrees.

Iron withholding, an essential component of nutritional immunity, plays a fundamental role in host resistance to Salmonella infection. Our previous study showed that SpvB, an important pSLT-encoded cytotoxic effector, facilitated Salmonella pathogenesis within macrophages via perturbing cellular iron metabolism. However, the underlying mechanisms of SpvB in Salmonella-relevant disorders of systemic iron metabolism have not yet been identified. Here, we demonstrated that SpvB facilitated Salmonella to scavenge iron from the host by modulating the hepcidin–ferroportin axis, a key regulator of systemic iron metabolism. We observed that SpvB enhanced hepatic hepcidin synthesis in a STAT3-dependent manner, but not the BMP/SMAD pathway. This subsequently resulted in a reduction of the unique cellular iron exporter ferroportin, which facilitated hypoferremia and hepatic iron accumulation and ultimately countered the limitation of iron availability, thereby improving the chances of Salmonella survival and replication. Moreover, SpvB promoted the production of proinflammatory molecules associated with the infiltration of inflammatory cells via highly upregulating TREM-1 signaling. Our data supported a role of TREM-1 in SpvB-related dysregulation of host iron metabolism and suggested that targeting TREM-1 might provide a potential therapeutic strategy to prevent or alleviate Salmonella pathogenesis.

Even though phenazines have been extensively reported as anticancer molecules, the molecular target of these compounds is severely lagging behind. Our study consequently focuses on the anticancer target of a phenazine analogue (CPUL1) for its potently antitumor activities in initial stage. Along with redox status courses of Hep G2 cells, thioredoxin reductase I (TrxR1) was speculated as anticancer target of CPUL1. By virtue of zymologic, immunological and molecular biological experiments, we demonstrated that TrxR1 could be the anticancer target of CPUL1. The knowledge on phenazine targeting to TrxR1 have not been reported previously. Thus, it can provide valuable information for further development of the TrxR1 inhibitors.

A strain of Microbacterium kitamiense capable of decomposing cellulose was obtained from the soil of Shigatse region in Tibet. Low temperature and cellulase gene MkCel5 was cloned and sequenced. The size of the open-reading frame was 1449 bp; it was predicted to encode a polypeptide with 482 residues with a molecular weight of 51.38 kDa. Sequence analysis indicated that it belongs to the glycoside hydrolase family 5 (GH5), which has high homology with reported endoglucanases. The predicted protein structure had a typical carbohydrate-binding domain and a catalytic domain of cellulase. Site mutagenesis experiments showed that the two glutamates at positions 312 and 404 were crucial in the catalytic process. MkCel5 was identified as a cold-adaptive and neutral enzyme with a maximum activity at 25 °C and pH 7.0. These properties suggested that MkCel5 has potential for application in the cellulose processing industry requiring low temperature.

Background: Patients with chronic kidney disease (CKD) often have CD4+ regulatory T cells (Tregs) dysfunction and chronic inflammation. We aim to investigate the effect, function, and related mechanism of low-dose IL-2 on CD4+ regulatory T cells expansion in vitro from patients with CKD. Methods: A total of 148 newly diagnosed patients with CKD at Stage III and 35 healthy volunteer subjects were recruited into our studies. The number of peripheral Tregs in peripheral blood mononuclear cells isolated from CKD patients, which were characterized by FACS as CD4+CD25hi and CD4+CD25+FoxP3+. The effect of low-dose IL-2 on expansion of Tregs, and the suppressive function of expanded Tregs were also analyzed by FACS. The levels of FoxP3 mRNA were detected by qRT-PCR. The activation of IL-2 induced Stat5 and blocking experiments were assessed by Western Blotting and FACS. Results: We found that the frequency of peripheral Tregs from CKD patients was significantly lower than that in healthy volunteer subjects. We also showed that IL-2 selectively expanded CD4+CD25hi and CD4+CD25+FoxP3+ regulatory T cells, and also upregulated the expression of FoxP3 mRNA. Our in vitro studies demonstrated that expanded CD4+ regulatory T cells from CKD patients suppressed proinflammatory Th1 and Th17 cell response. Furthermore, STAT5 activation is required for IL-2-induced expansion of regulatory T cells and expression of FoxP3 mRNA from CKD patients. Conclusions: Our findings support the clinical Treg defects in CKD patients with glomerular diseases, and the rationale of evaluating low-dose IL-2 treatment for selectively modulating CD4+ Tregs.

The aim of this case-control study was to investigate the correlation between the methylation levels of inhibitor of DNA binding 2 (Id2) gene and the incidence of tetralogy of Fallot (TOF) in children. The study included 31 TOF and 32 healthy control children. The methylation status of the Id2 gene was determined with time-of-flight mass spectrometry. Peripheral blood indices were detected, and their correlations with Id2 gene methylation were analyzed. Methylation analysis showed that there was no significant difference in the Id2 gene methylation level between the control and TOF groups (P > 0.05). After controlling the factors of gender, age, height and body weight, the analysis showed that there was no correlation between the methylation levels at each Id2 site and the red blood cells (RBC), hemoglobin (HGB) or hematocrit (HCT) (P > 0.05). However, the methylation levels at the CpG-16 and CpG-18.19 sites of the Id2 gene were negatively correlated with the mean corpuscular hemoglobin (MCH) (r = −0.337, P = 0.009; r = −0.392, P = 0.002) and mean corpuscular hemoglobin concentration (MCHC) (r = −0.363, P = 0.005; r = −0.286, P = 0.028), respectively. Our results suggest that the Id2 methylation might not be associated with the incidence of TOF. These results might contribute to the understanding of the etiology and mechanism of TOF in clinic.

Chitosan (CS)-acetylsalicylic acid (ASA) nanoparticles, which are well dispersed and stable in aqueous solution, have been prepared by interpolymer complexation of ASA in CS solution. The physicochemical properties of nanoparticles were investigated by using FT-IR, 1H NMR, scanning electron microscope（SEM）, dynamic light scattering, and UV spectrophotometer. It was found that the carboxyl group of the ASA had firmly integrated on the amino group of CS and the ASA-CS nanoparticles were almost spherical in shape with an average diameter of less than (79.3 ± 24.6) nm in high reproducibility and showed high chemical stability against environmental changes. It was also found that the prepared nanoparticles carried a positive charge and showed the size in the range from 700 to 150 nm. The surface structure and zeta potential of nanoparticles can be controlled by different preparation processes. The factor experiment results indicated that the ASA-CS nanoparticles had satisfactory loading capacity (LC) and encapsulation efficiency (EE), 27.27% and 46.88% (data not shown), respectively. The experiments of in vitro ASA release showed that these nanoparticles provided a sustained and pH-dependent drug release manner, and the release behavior was influenced by the pH value of the medium. Preliminary pharmacology experiment exhibited prolonged circulation and higher bioavailability than that of ASA. All the results indicated that ASA/CS nanoparticles may have promising pharmaceutical application, and further pharmacological research is needed to confirm these beneficial effects.

Objectives: Although low-dose computed tomography has been confirmed to have meaningful diagnostic utility, lung cancer is still the leading cause of cancer-related deaths for both genders worldwide. Thus, a novel panel with a stronger diagnostic performance for lung cancer is needed. This study aimed to investigate the efficacy of a new panel in lung cancer diagnosis. Materials and Methods: The serum levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and seven autoantibodies were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. The 316 candidates enrolled in this study were randomly assigned into two groups for the training and validation of a diagnostic panel. Results: An optimal panel with four biomarkers (CEA, CA125, Annexin A1-Ab, and Alpha enolase-Ab) was established, with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.897, a sensitivity of 86.5%, a specificity of 82.3%, a positive predictive value (PPV) of 88.3%, a negative predictive value (NPV) of 79.7%, and a diagnostic accuracy of 84.8% for the training group. The panel was validated, with an AUC of 0.856 and a sensitivity of 87.5% for the validation group. Furthermore, the new panel performed significantly better in lung cancer screening than did CEA and CA125 in all of the cohorts (p< .05). Conclusion: The diagnostic performance of CEA and CA125 was significantly enhanced through their combination with two autoantibodies (Annexin A1-Ab, and Alpha enolase-Ab). Optimization of the measured autoantibodies is critical for generating a panel to detect lung cancer in patients.

The present work aimed to apply the liquid antisolvent precipitation (LAP) method for preparing the apigenin nanoparticles and thereby improving the solubility and bioavailability of apigenin. The different experimental parameters on particle size were optimized through central composite design (CCD) using the Design-Expert® software. Under the optimum conditions, the particle size of the apigenin nanosuspension was about 159.2 nm. In order to get apigenin nanoparticles, the freeze-drying method was selected and the mannitol was used as a cryoprotectant. Then the solid state properties of the apigenin nanoparticles were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermo gravimetric (TG), and X-ray diffraction (XRD). The results obtained displayed that the apigenin nanoparticles exhibited near-spherical shape and could be transformed into an amorphous form. In addition, the dissolving test, the bioavailability in rats, and the antitumor activity were also studied. The experimental results showed that the solubility of the apigenin nanoparticles were about 29.61 times and 64.81 times of raw apigenin in artificial gastric juice and in artificial intestinal juice, respectively, and the apigenin nanoparticles showed higher dissolution rates compared to raw apigenin, and was about 6.08 times and 6.14 times than that of raw apigenin in artificial gastric juice and in artificial intestinal juice. The oral bioavailability of apigenin nanoparticles was about 4.96 times higher than that of the raw apigenin, but the apigenin nanoparticles had no toxic effect on the organs of rats. In addition, the apigenin nanoparticles had a higher inhibition to HepG2 cells by lower IC50 than that of raw apigenin.

A co-loaded drug delivery system based on ascorbyl palmitate that can transport various functional drugs to their targets within a tumor represents an attractive strategy for increasing the efficiency of anticancer treatment. In this study, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. AP, which is a vitamin C derivative, and PTX were incorporated into solid lipid nanoparticles (AP/PTX-SLNs), which were used to treat murine B16F10 melanoma that had metastasized to the lungs of mice. These nanoparticles were spherical with an average size of 223 nm as measured by transmission electron microscope and dynamic light scattering. In vitro cytotoxicity assays indicated that the AP/PTX-SLNs with an AP/PTX mass ratio of 2/1 provided the optimal synergistic anticancer efficacy. In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs than single drug (AP or PTX)-loaded SLNs via a synergistic effect through reducing the Bcl-2/Bax ratio. Furthermore, no marked side effects were observed during the treatment with the AP/PTX-SLNs, indicating that the co-delivery system with ascorbyl palmitate holds promising clinical potential in cancer therapy.

Here, the complete chloroplast genome of Keteleeria fortunei, a vulnerable species in China, was sequenced by next-generation sequencing platform. Its circular genome was 117,183 bp in length and the GC content was 38.5%. A total of 101 genes were annotated, including 4 rRNA genes, 20 tRNA genes, and 71 protein coding genes. This study would further our understanding of the genomics and the conservation and utilization of K. fortunei.

The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remains difficult despite the availability of numerous diagnostic tools. The current study aimed to evaluate the performance of the whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional laboratory biomarkers in differential diagnosis of TPE and MPE in high tuberculosis prevalence areas. A total of 117 patients with pleural effusions were recruited, including 91 with TPE and 26 with MPE. All of the patients were tested with QFT-GIT, and the conventional biomarkers in both blood and pleural effusion were detected. The level of antigen-stimulated QFT-GIT in the whole blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33 IU/mL, P

Laminated ZrC-SiC ceramic was prepared through tape casting and hot pressing. The green tapes of ZrC and SiC were prepared at room temperature. In order to improve the density of composite, the binder of green tapes were removed at 550 °C for 1 h. The laminated structure and the cracks propagation path, which is not a straight line, are observed by optical metalloscope. The compact laminated ZrC-SiC composite sintered by vacuum hot-pressing at 1650 °C for 90 min under pressure of 20 MPa was researched by X-ray diffraction and scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis. The results showed that interlayer bonding is tight, and no disordered phase has formed in the interlayers of ZrC or SiC, and the combination mode is physical mechanism.

Emerging Microbes & Infections (2017)6, e93; doi:10.1038/emi.2017.80; published online 1 November 2017

Understanding interactions between tumor and the host immune system holds great promise to uncover biomarkers for targeted therapies and clinical outcomes. However, systematical analysis of immune signatures in esophageal squamous cell carcinoma (ESCC) remains largely unstudied. In this study, immune signatures containing 708 immune related genes were curated from mRNA microarray data with tumor and paired normal tissues from 119 ESCC patients. Differential expression and survival analysis were performed with validations from Human Protein Atlas and an independent cohort of 110 ESCC patients by immunohistochemistry staining. We identified a total of 186 significantly dysregulated genes in ESCC, including downregulated genes SPINK5, IL1RN and upregulated genes SPP1 and PLAU, which were further confirmed in Human Protein Atlas data. Moreover, nine immune related genes (ABL1, ATF2, ATG5, C6, CD38, HMGB1, ICOSLG, IL12RB2 and PLAU) were significantly associated with patients' overall survival, among which, prognostic model was built including three independent factors ABL1, CD38 and ICOSLG. Validation by immunohistochemistry staining suggested that combination with tumor infiltrated CD4+ and CD8+ T lymphocytes would yield higher performance in distinguishing cases as high or low risk of unfavorable prognosis. In summary, we profiled the immune status in ESCC and established predictive and prognostic factors for ESCC, which could reflect immune disorders within tumor microenvironments and independently distinguish patients with a high risk of reduced survival, providing novel predictive and therapeutic targets for ESCC patients in the future.

Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear. Here, we aimed to determine if the extent of HBV DNA integration is associated with the persistence of circulating HBsAg in people exposed to HBV. We established a digital droplet quantitative inverse PCR (dd-qinvPCR) method to quantify integrated HBV DNA in patients who had been exposed to HBV (anti-HBc positive and HBeAg-negative). Total DNA extracts from both liver resections (n = 32; 14 HBsAg-negative and 18 HBsAg-positive) and fine-needle aspirates (FNA, n = 10; 2 HBsAg-negative and 8 HBsAg-positive) were analysed. Using defined in vitro samples for assay establishment, we showed that dd-qinvPCR could detect integrations within an input of