LiNi0.5Mn1.5O4 Joins to Alleviate Self-Discharge of Anion-Graphite Intercalation Compounds.

A straightforward hybrid approach of a blend cathode is put forward to alleviate self-discharged anion-graphite intercalation compounds in dual-ion batteries. The self-discharge mechanism of the LiNi0.5Mn1.5O4/graphite blend cathode is investigated by conventional electrochemical tests and in situ X-ray diffraction measurements. A charging behavior between electrode materials during self-discharge has been discovered. This work will contribute to advancing the practical implementation of dual-ion batteries and provide valuable theoretical support for the research of blend electrodes.

Ultrafast Charge and Long Life of High-Voltage Cathodes for Dual-Ion Batteries via a Bifunctional Interphase Nanolayer on Graphite Particles.

Dual-ion batteries (DIBs) with Co/Ni-free cathodes especially graphite cathodes are very attractive energy storage systems in the long run because of the cost effectiveness and sustainability. However, graphite cathodes severely suffer from poor structural stability during anions storage at high potentials owing to the oxidative decomposition of electrolytes and volume expansion. This work proposes an artificial cathode/electrolyte interphase (CEI) strategy by implanting polyphosphoric acid (PPA) nanofilms tightly on natural graphite (NG) particles via interfacial hydrogen bonding. The electrochemical results show that the PPA-modified graphite cathodes possess enhanced charge-discharge reversibility, accelerated electrode reaction kinetic, decreased resistance, decelerated self-discharge, and prolonged cycling life. Through post-analyses on the cycled graphite cathodes, the improved performance is mainly attributed to the PPA-based CEI, which effectively mitigates the electrolyte decomposition and protects the graphitic structure. More interestingly, the hydrogen bonding interactions between poly(vinyldifluoride) (PVDF) binder and PPA as validated through density functional theory calculations and practical experiments can increase the contact sites of PVDF chains on NG@PPA particles. Meanwhile, the cross-linking effect of PPA can enhance the mechanical strength of PVDF, thus the long life of NG@PPA cathode is also correlated with the improved mechanical stability of the entire electrode.

Associations between ambient air pollution and daily incidence of pediatric hand, foot and mouth disease in Ningbo, 2014-2016: a distributed lag nonlinear model.

Hand, foot and mouth disease (HFMD) has high prevalence around the world, with serious consequences for children. Due to the long survival period of HFMD virus in ambient air, air pollutants may play a critical role in HFMD epidemics. We collected data on daily cases of HFMD among children aged 0-14 years in Ningbo City between 2014 and 2016. Distributed lag nonlinear models were used to assess the effects of particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) on the daily incidence of HFMD among children, with analyses stratified by gender and age. Compared with moderate levels of air pollution, high SO2 levels had a relative risk (RR) of 2.32 (95% CI 1.42-3.79) and high NO2 levels had a RR of 2.01 (95% CI 1.22-3.31). The RR of O3 was 2.12 (95% CI 1.47-3.05) and that of PM2.5 was 0.77 (95% CI 0.64-0.92) at moderate levels of air pollution. Specifically, high levels of SO2 and NO2 had RRs of 2.39 (95% CI 1.44-3.96) and 2.02 (95% CI 1.21-3.39), respectively, among 0-4-year-old children, while high O3 had an RR of 2.31 (95% CI 1.09-4.89) among 5-14-year-old children. Our findings suggest significant associations of high SO2 and NO2 levels and moderate O3 levels in HFMD epidemics, and also indicate that air pollution causes lagged effects on HFMD epidemics. Our study provides practical and useful data for targeted prevention and control of HMFD based on environmental evidence.

Characterization of the spatial variability of soil available zinc at various sampling densities using grouped soil type information.

The influence of anthropogenic activities and natural processes involved high uncertainties to the spatial variation modeling of soil available zinc (AZn) in plain river network regions. Four datasets with different sampling densities were split over the Qiaocheng district of Bozhou City, China. The difference of AZn concentrations regarding soil types was analyzed by the principal component analysis (PCA). Since the stationarity was not indicated and effective ranges of four datasets were larger than the sampling extent (about 400 m), two investigation tools, namely F3 test and stationarity index (SI), were employed to test the local non-stationarity. Geographically weighted regression (GWR) technique was performed to describe the spatial heterogeneity of AZn concentrations under the non-stationarity assumption. GWR based on grouped soil type information (GWRG for short) was proposed so as to benefit the local modeling of soil AZn within each soil-landscape unit. For reference, the multiple linear regression (MLR) model, a global regression technique, was also employed and incorporated the same predictors as in the GWR models. Validation results based on 100 times realization demonstrated that GWRG outperformed MLR and can produce similar or better accuracy than the GWR approach. Nevertheless, GWRG can generate better soil maps than GWR for limit soil data. Two-sample t test of produced soil maps also confirmed significantly different means. Variogram analysis of the model residuals exhibited weak spatial correlation, rejecting the use of hybrid kriging techniques. As a heuristically statistical method, the GWRG was beneficial in this study and potentially for other soil properties.

Predict nutrition-related adverse outcomes in head and neck cancer patients undergoing radiotherapy: A systematic review.

BACKGROUND: Acute nutrition-related adverse outcomes are common in head and neck cancer patients undergoing radiotherapy. Predictive models can assist in identifying high-risk patients to enable targeted intervention. We aimed to systematically evaluate predictive models for predicting severe acute nutritional symptoms, insufficient intake, tube feeding, sarcopenia, and weight loss. METHODS: We searched PubMed, Web of Science, EBSCO, Embase, WanFang, CNKI, and SinoMed. We selected studies developing predictive models for the aforementioned outcomes. Data were extracted using a predefined checklist. Risk of bias and applicability assessment were assessed using the Prediction model Risk of Bias Assessment Tool. A narrative synthesis was conducted to summarize the model characteristics, risk of bias, and performance. RESULTS: A total of 2941 studies were retrieved and 19 were included. Study outcome measure were different symptoms (n = 11), weight loss (n = 5), tube feeding (n = 3), and symptom or tube feeding (n = 1). Predictive factors mainly encompassed sociodemographic data, disease-related data, and treatment-related data. Seventeen studies reported area under the curve or C-index values ranging from 0.610 to 0.96, indicating moderate to good predictive performance. However, candidate predictors were incomplete, outcome measures were diverse, and the risk of bias was high. Most of them used traditional model development methods, and only two used machine learning. CONCLUSIONS: Most current models showed moderate to good predictive performance. However, predictors are incomplete, outcome are inconsistent, and the risk of bias is high. Clinicians could carefully select the models with better model performance from the available models according to their actual conditions. Future research should include comprehensive and modifiable indicators and prioritize well-designed and reported studies for model development.

Effects of sodium hydroxide, sodium hypochlorite, and gaseous hydrogen peroxide on the natural properties of cancellous bone.

Processed xenegeneic cancellous bone represents an alternative to bone autograft. In order to observe the effects of present prion inactivation treatments on the natural properties of xenogeneic cancellous bones, we treated bovine bone granules with sodium hydroxide (NaOH), sodium hypochlorite (NaOCl), and gaseous hydrogen peroxide (gH2 O2 ) respectively in this study. The microstructure, composition, and mineral content of the granules were evaluated by scanning electron micrograph, energy dispersive X-ray spectroscopy, ash analysis, and micro-computed tomography. The biomechanical property was analyzed by a materials testing machine. The cytocompatibility was evaluated by using a mouse fibroblast cell line (3T3). The microstructure, organic content, and mechanical strength were dramatically altered at the surface of bone in both NaOH- and NaOCl-treated groups, but not in the gH2 O2 -treated group. Compared with the gH2 O2 -treated group, attachment and proliferation of 3T3 were reduced in either NaOH- or NaOCl-treated groups. As the consequence, gH2 O2 treatment may be a useful approach of disinfection for the preparation of natural cancellous bone with well-preserved structural, mechanical, and biological properties.

Development and Application of Portable Reflectometric Spectroscopy Combined with Solid-Phase Extraction for Determination of Potassium in Flue-Cured Tobacco Leaves.

Potassium (K) plays important roles in the energy and substance conversion of tobacco metabolism and is also regarded as one of the important indicators of tobacco quality evaluation. However, the K quantitative analytical method shows poor performance in terms of being easy-to-use, cost-effective, and portable. Here, we developed a rapid and simple method for the determination of K content in flue-cured tobacco leaves, including water extraction with 100 °C heating, purification with solid-phase extraction (SPE), and analysis with portable reflectometric spectroscopy based on K test strips. The method development consisted of optimization of the extraction and test strip reaction conditions, screening of SPE sorbent materials, and evaluation of the matrix effect. Under the optimum conditions, good linearity was observed in 0.20-0.90 mg/mL with a correlation coefficient >0.999. The extraction recoveries were found to be in the range of 98.0-99.5% with a repeatability and reproducibility of 1.15-1.98% and 2.04-3.26%, respectively. The sample measured range was calculated to be 0.76-3.68% K. Excellent agreement was found in accuracy between the developed reflectometric spectroscopy method and the standard method. The developed method was applied to analyze the K content in different cultivars, and the content varied greatly among the samples with lowest and highest contents for Y28 and Guiyan 5 cultivars, respectively. This study can provide a reliable approach for K analysis, which may become available on-site in a quick on-farm test.

Electrochemistry-Driven Interphase Doubly Protects Graphite Cathodes for Ultralong Life and Fast Charge of Dual-Ion Batteries.

Dual-ion batteries (DIBs) with graphite as cathode material, show superiority in terms of sustainability, affordability, and environmental impact over Li-ion batteries that rely on transition-metal based cathodes. However, graphite cathodes severely suffer from poor structural stability during anion storage at high potentials because of the co-intercalation and oxidative decomposition of electrolytes. This work presents an in situ electrochemistry-driven route to create a bifunctional interphase through implantation of diethylenetriaminepenta(methylene-phosphonic acid) (DTPMP) on the surface of graphite particles. The reaction mechanisms and functions of DTPMP are investigated both experimentally and theoretically. The DTPMP-derived interphase not only improves the antioxidative stability of electrolytes but also benefits the desolvation of PF6 - anions, which doubly protect the graphitic structure and give rise to fast-charge and ultralong cycling performance of graphite cathodes in DIBs.

Study on the Effect of Secondary Injection on the Combustion and Emission of n-Butanol Engines.

n-Butanol, as a biological alternative fuel containing oxygen, has similar physical and chemical properties to gasoline and has a wide range of sources, which has attracted more and more attention and research. Direct injection technology has been widely used in the field of internal combustion engine due to its advantages of flexibility and control ability. In this paper, the secondary injection of n-butanol engine under the mode of in-cylinder direct injection is discussed to organize stratified combustion of the mixture, optimize combustion to improve the thermal efficiency, and reduce emission. A four-cylinder four-stroke spark ignition (SI) engine was selected to carry out the secondary injection experiment of n-butanol under the excess air ratio (λ) of 1, an engine speed of 1500 r/min, and a low load, and the variables were the second injection ratio and timing. The results show that the secondary injection of n-butanol can achieve stratified combustion of the mixture, but only at a specific second injection timing such as 100°CA before compression top dead center (BTDC) or 125°CA BTDC, the combustion effect is the best. A small second injection ratio can optimize combustion, improve brake thermal efficiency, and reduce hydrocarbon and carbon monoxide emissions. When the second injection ratio is greater than 60%, it results in incomplete fuel combustion, a 3 to 4% reduction in thermal efficiency, and an increase in emissions. Coefficient of variation (COV) was increased by secondary injection, but the effect was insignificant in the small injection ratio, and it will increase with the increase of the second injection ratio. The change of particle number is mainly affected by the nuclear particle number, and with the increase of the second injection ratio, the total particulate number is more affected by the second injection timing. The second injection ratio of 40% can reduce the total particle number under the mixed-gas stratification condition.

Modified Laparoscopic Anatomic Hepatectomy: Two-Surgeon Technique Combined with the Simple Extracorporeal Pringle Maneuver.

Laparoscopic anatomic hepatectomy (LAH) has become increasingly prevalent worldwide in recent years. However, LAH remains a challenging procedure due to the anatomical characteristics of the liver, with intraoperative hemorrhage being a primary concern. Intraoperative blood loss is the leading cause of conversion to open surgery; therefore, effective management of bleeding and hemostasis is crucial for a successful LAH. The two-surgeon technique is proposed as an alternative to the traditional single-surgeon approach, with potential benefits in reducing intraoperative bleeding during laparoscopic hepatectomy. However, there remains a lack of evidence to determine which mode of the two-surgeon technique yields superior patient outcomes. Besides, to our knowledge, the LAH technique, which involves the use of a cavitron ultrasonic surgical aspirator (CUSA) by the primary surgeon while an ultrasonic dissector by the second surgeon, has been rarely reported before. Herein, we present a modified, two-surgeon LAH technique, wherein one surgeon employs a CUSA while the other uses an ultrasonic dissector. This technique is combined with a simple extracorporeal Pringle maneuver and low central venous pressure (CVP) approach. In this modified technique, the primary and secondary surgeons utilize a laparoscopic CUSA and an ultrasonic dissectorconcurrently to achieve precise and expeditious hepatectomy. A simple extracorporeal Pringle maneuver, combined with the maintenance of low CVP, is employed to regulate the hepatic inflow and outflow in order to minimize intraoperative bleeding. This approach facilitates the attainment of a dry and clean operative field, which allows for the precise ligation and dissection of blood vessels and bile ducts. The modified LAH procedure is simpler and safer due to its effective control over bleeding as well as the seamless transition between the roles of primary and secondary surgeons. It holds great promise for future clinical applications.

Effects of CpG sites methylation modification of HPV16 integration essential gene on the proliferation of cervical cancer cells.

PURPOSE: The mechanism of methylation of HPV CpG sites in the occurrence and prognosis of cervical carcinogenesis remains unclear. We investigated the effects of demethylation of the CpG sites of E2 and E6, essential genes of HPV16 integration, on cervical cancer cell expression, integration, and proliferation. MATERIALS AND METHODS: HPV16-positive (Caski) cells were treated with different concentrations of the demethylation compound 5-aza-dc (0, 5, 10, 20 µmol/l) in vitro. After the intervention, the methylation statuses of HPV16 E2 and E6 were detected by TBS, the expression levels of E2 and E6 mRNA and protein were detected by real-time PCR and western blot, cell proliferation activity was detected by CCK8, and cell cycle and apoptosis were determined by FCM. GraphPad Prism version 8.4.2 and R version 4.2.3 were used for relevant data analyses. RESULTS: The methylation levels of HPV16 E2 and E6 CpG sites decreased gradually with increasing 5-aza-dc intervention concentrations. With decreasing E2 and E6 methylation rates, E2 expression increased, the E2/E6 ratio increased, E6 expression decreased, and the growth inhibition rate of Caski cells increased. E2 and E6 expression were negatively and positively correlated with their degrees of methylation respectively, while the E2/E6 mRNA to protein ratio was negatively correlated with the methylation degrees of E2 and E6. CONCLUSION: Demethylation can be used as a prospective treatment to affect HPV expression and persistent infection, providing a new theoretical basis for the clinical treatment of viral infections.

NIR-II fluorescence-guided liver cancer surgery by a small molecular HDAC6 targeting probe.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and ranks third in terms of both mortality and incidence rates. Surgical resection holds potential as a curative approach for HCC. However, the residual disease contributes to a high 5-year recurrence rate of 70%. Due to their excellent specificity and optical properties, fluorescence-targeted probes are deemed effective auxiliary tools for addressing residual lesions, enabling precise surgical diagnosis and treatment. Research indicates histone deacetylase 6 (HDAC6) overexpression in HCC cells, making it a potential imaging biomarker. This study designed a targeted small-molecule fluorescent probe, SeCF3-IRDye800cw (SeCF3-IRD800), operating within the Second near-infrared window (NIR-II, 1000-1700 nm). The study confirms the biocompatibility of SeCF3-IRD800 and proceeds to demonstrate its applications in imaging in vivo, fluorescence-guided surgery (FGS) for liver cancer, liver fibrosis imaging, and clinical samples incubation, thereby preliminarily validating its utility in liver cancer. METHODS: SeCF3-IRD800 was synthesized by combining the near-infrared fluorescent dye IRDye800cw-NHS with an improved HDAC6 inhibitor. Initially, a HepG2-Luc subcutaneous tumor model (n = 12) was constructed to investigate the metabolic differences between SeCF3-IRD800 and ICG in vivo. Subsequently, HepG2-Luc (n = 12) and HCCLM3-Luc (n = 6) subcutaneous xenograft mouse models were used to assess in vivo targeting by SeCF3-IRD800. The HepG2-Luc orthotopic liver cancer model (n = 6) was employed to showcase the application of SeCF3-IRD800 in FGS. Liver fibrosis (n = 6) and HepG2-Luc orthotopic (n = 6) model imaging results were used to evaluate the impact of different pathological backgrounds on SeCF3-IRD800 imaging. Three groups of fresh HCC and normal liver samples from patients with liver cancer were utilized for SeCF3-IRD800 incubation ex vivo, while preclinical experiments illustrated its potential for clinical application. FINDINGS: The HDAC6 inhibitor 6 (SeCF3) modified with trifluoromethyl was labeled with IRDy800CW-NHS to synthesize the small-molecule targeted probe SeCF3-IRD800, with NIR-II fluorescence signals. SeCF3-IRD800 was rapidly metabolized by the kidneys and exhibited excellent biocompatibility. In vivo validation demonstrated that SeCF3-IRD800 achieved optimal imaging within 8 h, displaying high tumor fluorescence intensity (7658.41 ± 933.34) and high tumor-to-background ratio (5.20 ± 1.04). Imaging experiments with various expression levels revealed its capacity for HDAC6-specific targeting across multiple HCC tumor models, suitable for NIR-II intraoperative imaging. Fluorescence-guided surgery experiments were found feasible and capable of detecting sub-visible 2 mm tumor lesions under white light, aiding surgical decision-making. Further imaging of liver fibrosis mice showed that SeCF3-IRD800's imaging efficacy remained unaffected by liver pathological conditions. Correlations were observed between HDAC6 expression levels and corresponding fluorescence intensity (R2 = 0.8124) among normal liver, liver fibrosis, and HCC tissues. SeCF3-IRD800 identified HDAC6-positive samples from patients with HCC, holding advantages for perspective intraoperative identification in liver cancer. Thus, the rapidly metabolized HDAC6-targeted small-molecule NIR-II fluorescence probe SeCF3-IRD800 holds significant clinical translational value. INTERPRETATION: The successful application of NIR-II fluorescence-guided surgery in liver cancer indicates that SeCF3-IRD800 has great potential to improve the clinical diagnosis and treatment of liver cancer, and could be used as an auxiliary tool for surgical treatment of liver cancer without being affected by liver pathology. FUNDING: This paper is supported by the National Natural Science Foundation of China (NSFC) (92,059,207, 62,027,901, 81,930,053, 81,227,901, 82,272,105, U21A20386 and 81,971,773), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), and Guangdong Basic and Applied Basic Research Foundation under Grant No. 2022A1515011244.

Study on Combustion and Emissions of a Combined Injection Spark Ignition Engine with Natural Gas Direct Injection Plus Ethanol Port Injection under Lean-Burn Conditions.

Conventional ethanol spark ignition (SI) engines have poor fuel atomization and mixture formation. The objective of this paper is to improve the combustion and emission performance of ethanol SI engines under lean-burn conditions through the dual-injection mode with ethanol port injection and compressed natural gas (CNG) direct injection (CDI+EPI). This paper studies the engine performance at 1500 rpm under five CNG direct injection ratios (CDIr) and five excess air ratios (λ). The results show that as the CDIr increases under lean-burn conditions, the following occurs: the minimum advance for best torque (MBT), the coefficient of variation (CoVIMEP), and CO and HC emissions decrease; the crankshaft rotation or time with cumulative heat release rate ranging from 10% to 90% (CA 10-90) and NOx emissions first decrease and then increase; and torque, peak in-cylinder pressure (Pmax), and the λ limit first increase and then decrease. The larger the CDIr is, the less influence λ has on the MBT. When CDIr = 15%, the CoVIMEP can be effectively reduced, the engine can still work stably in all lean-burn conditions, and the λ limit will reach the maximum value of 1.73, 19.31% higher than that of the original engine (CDIr = 0). When λ = 1.1, CO emissions decrease the most and HC emissions decrease the least. At this time, CO and HC emissions decrease by 1.56 vol % and 30 ppm, respectively, on average for every 0.1 decrease in λ. For CA 10-90, torque, and Pmax, λ = 1.1, 15% CDI, and 85% EPI is the optimal combination under lean-burn conditions. When CDIr ≥ 15%, NOx emissions are at an ideal level. Under lean-burn conditions, direct-injection CNG can form a good stratified natural gas/ethanol mixture in the cylinder, effectively improving the engine's power and stability and reducing emissions. The λ = 1.1, 15% CDI, 85% EPI combination provides a cutting-edge and outstanding solution for a natural gas/ethanol combined injection SI engine.

Effect of Exhaust Gas Recirculation and Spark Timing on Combustion and Emission Performance of an Oxygen-Enriched Gasoline Engine.

Oxygen-enriched combustion (OEC) technology in SI engines can greatly improve the degree of constant volume combustion, increase the torque output, and reduce HC and CO emissions but lead to a sharp increase in NO x emissions. Simultaneously, the high temperature from OEC would lead to high nucleation particle emissions. Under the OEC mode, except the oxygen content, spark timing and engine load are important influencing factors on emissions. Exhaust gas recirculation (EGR) technology has been proven to reduce NO x emissions effectively. This research investigates the effects of EGR on combustion and emission performance under an oxygen-enriched ratio (OER) of 25% with five EGR ratios (0-20%) for the initial throttle opening of 14% (at an EGR ratio of 0%) with an engine speed of 1500 rpm. The study shows that when the OER is 25%, the output torque increases with the increase of the EGR ratio. At the proper spark timing, the EGR ratio over 15% can obtain lower NO x emissions and particle emissions than the baseline (OER of 21%). Although HC emissions increase with the EGR ratio, they are still lower than the baseline. Overall, the OER of 25% coupled with the EGR ratios of 15-20% is the predominant combustion mode to improve power and emission performance in SI engines.

THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.

Follistatin Alleviates Hepatic Steatosis in NAFLD via the mTOR Dependent Pathway.

Purpose: In this study, we aimed to investigate the effect of follistatin (FST) on hepatic steatosis in NAFLD and the underlying mechanism, which has rarely been reported before. Methods: Liver samples from NAFLD patients and normal liver samples (from liver donors) were collected to investigate hepatic FST expression in humans. Additionally, human liver cells (LO2) were treated with free fatty acid (FFA) to induce lipid accumulation. Furthermore, lentivirus with FST overexpression or knockdown vectors were used to generate stable cell lines, which were subsequently treated with FFA or FFA and rapamycin. In the animal experiments, male C57BL/6J mice were fed with a high-fat diet (HFD) to induce NAFLD, after which the adeno-associated virus (AAV) gene vectors for FST overexpression were administered. In both cell culture and mice, we evaluated morphological changes and the protein expression of sterol regulatory element-binding protein1 (SREBP1), acetyl-CoA carboxylase1 (ACC1), carbohydrate-responsive element-binding protein (ChREBP), fatty acid synthase (FASN), and Akt/mTOR signaling. The body weight and serum parameters of the mice were also measured. Results: Hepatic FST expression level was higher in NAFLD patients compared to normal samples. In LO2 cells, FST overexpression alleviated lipid accumulation and lipogenesis, whereas FST knockdown aggravated hepatic steatosis. FST could regulate Akt/mTOR signaling, and the mTOR inhibitor rapamycin abolished the effect of FST knockdown on hepatic de novo lipogenesis (DNL). Furthermore, FST expression was increased in HFD mice compared to the corresponding controls. FST overexpression in mice reduced body weight gain, hyperlipidemia, hepatic DNL, and suppressed Akt/mTOR signaling. Conclusion: Hepatic FST expression increases in NAFLD and plays a protective role in hepatic steatosis. FST overexpression gene therapy alleviates hepatic steatosis via the mTOR pathway.Therefore, gene therapy for FST is a promising treatment in NAFLD.

Copper migration and isotope fractionation in a typical paddy soil profile of the Yangtze Delta.

To decipher Cu migration in paddy soils, which is important for understanding Cu supply in rice cultivation, Cu concentrations and isotope compositions were measured in a paddy soil profile in Suzhou, Eastern China, in the central Yangtze Delta. The results show that the variations in δ65Cu values and Cu concentrations are not coupled along the profile. From top to bottom, the δ65Cu values show small variations (0.07 ± 0.03‰ to 0.25 ± 0.01‰) in the upper layers (Ap-Br1), with a decrease in the subsurface Br2 layer (from 0.16 ± 0.04‰ to -0.19 ± 0.02‰), are almost homogeneous in the transitional Br3-BCrg layers (-0.01 ± 0.01‰ to -0.10 ± 0.02‰), and further decrease to -0.33 ± 0.01‰ in the permanently submerged G1 and G2 layers. Copper concentrations in the Ap layer show some fluctuations (25.8 to 29.0 µg/g), increase in the Br2 and Br3 layers (23.9 µg/g to 31.9 µg/g), and then decrease to 15.1 µg/g in the lower layers. The lack of coupling between δ65Cu values and Cu concentrations may be ascribed to various physicochemical conditions in different layers. In the upper layers, Cu(I) enriched in light isotopes migrates downward with soil solutions under flooded conditions, leaving the soils of the Ap and Br1 layers enriched in heavy Cu isotopes. In the Br2 layer, the readsorption of light Cu isotopes on clay minerals results in decreased δ65Cu values and increased Cu concentrations. In the Br3-BCrg layers, Cu(I) can be oxidized to Cu(II). The homogeneous Cu isotopes in these layers may mainly result from equilibrium adsorption of Cu on clay minerals. The decreased δ65Cu values and Cu concentrations in the G layer are mainly attributed to groundwater transport in this layer. This study represents the Cu isotope variations in a paddy soil profile and the possible mechanism of Cu isotope fractionation.

Mapping high resolution National Soil Information Grids of China.

Soil spatial information has traditionally been presented as polygon maps at coarse scales. Solving global and local issues, including food security, water regulation, land degradation, and climate change requires higher quality, more consistent and detailed soil information. Accurate prediction of soil variation over large and complex areas with limited samples remains a challenge, which is especially significant for China due to its vast land area which contains the most diverse soil landscapes in the world. Here, we integrated predictive soil mapping paradigm with adaptive depth function fitting, state-of-the-art ensemble machine learning and high-resolution soil-forming environment characterization in a high-performance parallel computing environment to generate 90-m resolution national gridded maps of nine soil properties (pH, organic carbon, nitrogen, phosphorus, potassium, cation exchange capacity, bulk density, coarse fragments, and thickness) at multiple depths across China. This was based on approximately 5000 representative soil profiles collected in a recent national soil survey and a suite of detailed covariates to characterize soil-forming environments. The predictive accuracy ranged from very good to moderate (Model Efficiency Coefficients from 0.71 to 0.36) at 0-5 cm. The predictive accuracy for most soil properties declined with depth. Compared with previous soil maps, we achieved significantly more detailed and accurate predictions which could well represent soil variations across the territory and are a significant contribution to the GlobalSoilMap.net project. The relative importance of soil-forming factors in the predictions varied by specific soil property and depth, suggesting the complexity and non-stationarity of comprehensive multi-factor interactions in the process of soil development.

Combined Treatment of Tanshinone I and Epirubicin Revealed Enhanced Inhibition of Hepatocellular Carcinoma by Targeting PI3K/AKT/HIF-1α.

Background: Epirubicin (EADM) is a common chemotherapeutic agent in hepatocellular carcinoma (HCC). The accumulation of hypoxia-inducible factor-1α (HIF-1α) is an important cause of drug resistance to EADM in HCC. Tanshinone I (Tan I) is an agent with promising anti-cancer effects alone or with other drugs. Some tanshinones mediate HIF-1α regulation via PI3K/AKT. However, the role of Tan I combined with EADM to reduce the resistance of HCC to EADM has not been investigated. Therefore, this study aimed to investigate the combined use of Tan I and EADM in HCC and the underlying mechanism of PI3K/AKT/HIF-1α. Methods: HCC cells were treated with Tan I, EADM, or the combined treatment for 48 hrs. Cell transfection was used to construct HIF-1α overexpression HCC stable cells. Cell viability, colony formation, and flow cytometric assays were used to detect the viability, proliferation, and apoptosis in HCC cells. Synergism between Tan I and EADM were tested by calculating the Bliss synergy score, positive excess over bliss additivism (EOBA), and the combination index (CI). Western blotting analyses were used to detect the levels of ß-actin, HIF-1α, PI3K p110α, p-Akt Thr308, Cleaved Caspase-3, and Cleaved Caspase-9. Toxicity parameters were used to evaluate the safety of the combination in mice. The xenograft model of mice was built by HCC stable cell lines, which was administrated with Tan I, EADM, or a combination of them for 8 weeks. Immunohistochemistry staining (IHC) was used to assess tumor apoptosis in mouse models. Results: Hypoxia could upregulate HIF-1α to induce drug resistance in HCC cancer cells. The combination of Tan I and EADM was synergistic. Although Tan I or EADM alone could inhibit HCC cancer cells, the combination of them could further enhance the cytotoxicity and growth inhibition by targeting the PI3K/AKT/HIF-1α signaling pathway. Furthermore, Tan I and EADM synergistically reversed HIF-1α-mediated drug resistance to inhibit HCC. The results of toxicity parameters showed that the combination was safe in mice. Meanwhile, animal models showed that Tan I not only improved the anti-tumor effect of EADM, but also reduced the drug reactions of EADM-induced weight loss. Conclusion: Our results suggested that Tan I could effectively improve the anti-tumor effect of EADM, and synergize EADM to reverse HIF-1α mediated resistance via targeting PI3K/AKT/HIF-1α signaling pathway.

Significant loss of soil inorganic carbon at the continental scale.

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and CO2 release. However, to date, few studies have addressed these processes. Here, we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon (SIC) stocks in China. We observe an overall decrease in SIC stocks in topsoil (0-30 cm) (11.33 g C m-2 yr-1) from the 1980s to the 2010s. Total SIC stocks have decreased by ∼8.99 ± 2.24% (1.37 ± 0.37 Pg C). The average SIC losses across China (0.046 Pg C yr-1) and in cropland (0.016 Pg C yr-1) account for ∼17.6%-24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland, respectively. Nitrogen deposition and climate change have profound influences on SIC cycling. We estimate that ∼19.12%-19.47% of SIC stocks will be further lost by 2100. The consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration, which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.