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The difficulty in grain refinement during the casting of superalloy turbine guides is the primary factor of their low percent of pass. This study innovatively employs the electromagnetic oscillation (EMO) process during pouring and solidification using self-developed device to break through this problem. The effect of various process parameters on blade microstructure is also investigated. The result shows that implementing 300 A/20 Hz optimal EMO process produces uniformly fine equiaxed grains, reducing average grain sizes by 71.83% at the blade concave and 75.80% at the inlet edge. Yield and tensile strength increased by 22.34% and 27.15%, respectively, reaching a tensile strength of 1208.09 MPa. Elongation and section shrinkage also increased by 69.67% and 19.57%, respectively. The forced oscillation of melt caused by alternating magnetic field flushes and fragments dendrites, creating numerous nucleation sites, thus promoting grain refinement. The current intensity is linearly correlated with the electromagnetic force within the melt, influencing consequent oscillation effects. The optimal electromagnetic oscillation penetration depth, calculated at 42 mm, is determined by the number of oscillations and skin effect. This depth, calculated based on the inherent properties of the alloy, is instrumental in ascertaining the optimum current frequency for this model of turbine guides, applicable across different alloy compositions. The tensile deformation behavior of castings is altered by the grain refinement induced by the EMO process, enhancing tensile properties through the promotion of more homogeneous deformation and the inhibition effect of grain boundaries and one-dimensional defects on dislocations.

ObjectiveTo compare the efficacy of trastuzumab plus pertuzumab (HP) combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice. MethodsClinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021. The total pathological complete response (tpCR) rates of the two groups were compared. ResultsA total of 76 patients were included in the study, with 47 in the nab-paclitaxel group and 29 in the docetaxel group. The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group (72.3% vs. 48.3%, χ2=4.463, P=0.035). Subgroup analysis indicated that patients older than 40 years, with cN2-3, cTNM stage Ⅲ, hormone receptor-positive status, and Ki67>30% had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group (P

Abstract One-dimensional carbon nanotubes are promising candidates for thermoelectrics because of their excellent electrical and mechanical properties. However, the large n-type power factor remains elusive in macroscopic carbon nanotubes films. Herein, we report an outstanding n-type power factor of 6.75 mW m−1 K−2 for macroscopic carbon nanotubes films with high electrical and thermal conductivity. A high-power density curl-able thermoelectric generator is fabricated with the obtained carbon nanotubes films, which exhibits a high normalized power output density of 2.75 W m−1 at a temperature difference of 85 K. The value is higher than that of previously reported flexible all-inorganic thermoelectric generators (

IntroductionEnhancing the efficacy of online food safety supervision requires thoughtful selection and efficient application of regulatory measures.MethodsThis study examined the current state of online food safety supervision in the important food producing city in central China of Zhengzhou. The effectiveness of supervision frequency and penalty on food safety governance of online catering was examined through model construction based on the optimal law enforcement theory. The efficacy of monitoring was evaluated using real supervision and punishment data from the online catering sector in a Chinese new first-tier city.Results and discussionResults showed that although high-frequency and high-penalty supervision are two common methods of online food safety governance, the deterrent effect of high-frequency supervision on online food businesses is more significant for improving the supervision efficiency of the online catering market. Simultaneously, bolstering the education of caterers and food operators as well as raising their degree of training are also efficient ways to raise the efficacy of government oversight. The application of law enforcement economics is broadened in this study, which also has implication for the advancement of credit rating and classification supervision in the area of food safety for online catering.

The identification of rock-breaking mode is a key basis to improve cutting ability, and the cutter cutting attitude has a significant influence on rock-breaking mode. In this study, the internal relationship between cutting attitude and rock-breaking mode was explored, and the optimal cutting attitude parameters of low energy consumption and high efficiency rock-breaking were inferred. Based on the massive collapse state of the wedge surface acting rock when disc cutter vibrates axially upward, the rock tensile-shear coupling failure condition was given according to the Mohr-Coulomb criterion on the basis of the nonlinear rock failure criterion, and the three-segment linear rock failure global criterion (tensile failure, tensile-shear coupling failure, shear failure, compression-shear coupling failure and compression failure) was obtained. The mathematical description of the cutter wedge surface compressive stress under different rock-breaking modes was got. Based on the principle of minimum energy of the wedge surface action, the identification method of rock-breaking mode was proposed, and the load model of cutting rock with disc cutter of oblique attitude was constructed. The correlation between load characteristics of the cutter, rock-crushing characteristics (rock fragmentation distribution and dust size distribution) and rock-breaking mode under different cutting attitude inclination angles was analyzed by numerical simulation and experiment. The results show that the characterization values of wedge surface energy consumption of disc cutter are proportional to the attitude inclination angle, and rock-breaking mode changes from tensile-shear coupling failure to compressive-shear coupling failure. The characterization values of wedge surface energy consumption of disc cutter in vibration cutting are obviously less than that in non-vibration cutting, and it is mainly caused by tensile-shear coupling failure, while the tension-shear and compression-shear coupling failure exists approximately in equal proportion in non-vibration cutting. When the wedge surface component of axial velocity is greater than that of feed velocity, the friction is transformed into rock-breaking assistance, and the energy consumption of the wedge surface is significantly reduced. The macroscopic morphology of disc cutter breaking rock is like the large crescent shape, and the microscopic morphology of the rock powder is like polyhedron and spheroid. The attitude inclination angle of the cutter is inversely proportional to the amount of the rock fragments, and is proportional to the amount of the rock powder (spherical-like dust decreases and polyhedron-like dust increases). It indicates that as the attitude inclination angle increases, the extrusion effect of the cutter teeth edge is weakened, and the energy consumption of dust generated by the wedge surface extrusion increases, which is consistent with the influence of the cutting attitude on the energy consumption of the wedge surface during the identification process of rock-breaking mode. The radial load and the attitude inclination angles of disc cutter are concave, the theory and simulation are consistent with the experimental radial load law, and the average errors are 8.46% and 9.55%, respectively. The rationality of the identification method of disc cutter rock-breaking mode, the load model of cutting rock with inclined attitude and the numerical simulation is verified.

Abstract Objective To evaluate the effect of mind–body exercise on improving knee osteoarthritis (KOA) and thereby informing osteoarthritis exercise rehabilitation. Methods The China National Knowledge Infrastructure (CNKI), Wanfang, PubMed/Medline, Cochrane Library, Web of Science, EBSCO, Embase, Scopus, and ProQuest databases were searched to identify randomized controlled trials (RCTs) that involved tai chi, yoga, and baduanjin interventions for KOA. The search period ranged from inception to October 25, 2022. The methodological quality of the included studies was evaluated by the Cochrane risk of bias assessment tool, and the included data were statistically analyzed and plotted using Review Manager 5.3 and Stata 14.0 software. Results We included 17 articles with a total of 1122 patients. Compared with the control group, mind–body exercise significantly improved patient pain (standardized mean difference (SMD) = -0.65, 95% confidence interval (CI) [-0.87, -0.42], p

Summary: Background: The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. Methods: We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020 at 11 centres, and collected triple-phase CT images and laboratory results 3–12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n = 924), and then validated in an internal validation cohort (n = 231), and an external validation cohort from 10 external centres (n = 703). Findings: We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918–0.941) in the discovery cohort, 0.902 (0.818–0.987) in the internal validation cohort, and 0.918 (0.898–0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n = 221, 11.9%) and medium-risk (n = 433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P

Abstract Background Host-microbial interactions are expected to affect species’ adaptability to climate change but have rarely been explored in ectothermic animals. Some studies have shown that short-term warming reduced gut microbial diversity that could hamper host functional performance. Results However, our longitudinal experiments in semi-natural conditions demonstrated that warming decreased gut microbiota diversity at 2 months, but increased diversity at 13 and 27 months in a desert lizard (Eremias multiocellata). Simultaneously, long-term warming significantly increased the antibacterial activity of serum, immune responses (higher expression of intestinal immune-related genes), and the concentration of short-chain fatty acids (thereby intestinal barrier and immunity) in the lizard. Fecal microbiota transplant experiments further revealed that increased diversity of gut microbiota significantly enhanced antibacterial activity and the immune response of lizards. More specifically, the enhanced immunity is likely due to the higher relative abundance of Bacteroides in warming lizards, given that the bacteria of Bacteroides fragilis regulated IFN-β expression to increase the immune response of lizards under a warming climate. Conclusions Our study suggests that gut microbiota can help ectotherms cope with climate warming by enhancing host immune response, and highlights the importance of long-term studies on host-microbial interactions and their biological impacts. Graphical Abstract Video Abstract

Abstract Background Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. Methods The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. Results Four predictors were selected from 38 variables by the univariate analysis (p

The pinewood nematode (Bursaphelenchus xylophilus, PWN) induces pine wilt disease in Pinaceae plants, causing severe destruction to pine forests. Previous studies report that by 2023, 663 cities across 18 provinces in China had been infested by the PWN, necessitating immediate control measures. To identify the genetic variations associated with the PWN’s adaptation to new environments, we conducted whole-genome sequencing (WGS) on 13 indigenous PWN samples from two distinct geographic zones within China, specifically Anhui, Liaoning, and Jiangxi provinces. We identified genetic variants and analyzed the genetic structure of these populations, followed by functional gene enrichment analyses. Our findings reveal genetic variants associated with secretion, immune system function, membrane processes, metabolism, catabolism, and cell wall regulation, supporting the hypothesis that the PWN genome has been shaped by local ecosystems.

Using the near-detailed-balance distribution function obtained in our recent work, we present a set of covariant gravito-thermal transport equations (i.e. the flow of various charges as linear response to thermodynamical forces) for neutral relativistic gases in a generic stationary spacetime. All relevant tensorial transport coefficients are worked out and are presented using some particular integration functions in (α,ζ), where α=−βμ and ζ=βm is the relativistic coldness, with β being the inverse temperature and μ being the chemical potential. It is shown that the Onsager reciprocal relation holds in the gravito-thermal transport phenomena, and that the heat conductivity and the gravito-conductivity tensors are proportional to each other, with the coefficient of proportionality given by the product of the so-called Lorenz number with the temperature, thus proving a gravitational variant of the Wiedemann-Franz law. It is remarkable that, for strongly degenerate Fermi gases, the Lorenz number takes a universal constant value L=π2/3, which extends the Wiedemann-Franz law into the Wiedemann-Franz-Lorenz law.

Background: Sertraline is a commonly employed antidepressant in clinical practice. In order to control the plasma concentration of sertraline within the therapeutic window to achieve the best effect and avoid adverse reactions, a personalized model to predict sertraline concentration is necessary.Aims: This study aimed to establish a personalized medication model for patients with depression receiving sertraline based on machine learning to provide a reference for clinicians to formulate drug regimens.Methods: A total of 415 patients with 496 samples of sertraline concentration from December 2019 to July 2022 at the First Hospital of Hebei Medical University were collected as the dataset. Nine different algorithms, namely, XGBoost, LightGBM, CatBoost, random forest, GBDT, SVM, lasso regression, ANN, and TabNet, were used for modeling to compare the model abilities to predict sertraline concentration.Results: XGBoost was chosen to establish the personalized medication model with the best performance (R2 = 0.63). Five important variables, namely, sertraline dose, alanine transaminase, aspartate transaminase, uric acid, and sex, were shown to be correlated with sertraline concentration. The model prediction accuracy of sertraline concentration in the therapeutic window was 62.5%.Conclusion: In conclusion, the personalized medication model of sertraline for patients with depression based on XGBoost had good predictive ability, which provides guidance for clinicians in proposing an optimal medication regimen.

Abstract Background Percutaneous cannulation is now accepted as the first-line strategy for extracorporeal cardiopulmonary resuscitation (ECPR) in adults. However, previous studies comparing percutaneous cannulation to surgical cannulation have been limited by small sample size and single-center settings. This study aimed to compare in-hospital outcomes in cardiac arrest (CA) patients who received femoro-femoral ECPR with percutaneous vs surgical cannulation. Methods Adults with refractory CA treated with percutaneous (percutaneous group) or surgical (surgical group) femoro-femoral ECPR between January 2008 and December 2019 were extracted from the international Extracorporeal Life Support Organization registry. The primary outcome was severe neurological complication. Multivariable logistic regression analyses were performed to assess the association between percutaneous cannulation and in-hospital outcomes. Results Among 3575 patients meeting study inclusion, 2749 (77%) underwent percutaneous cannulation. The proportion of patients undergoing percutaneous cannulation increased from 18% to 89% over the study period (p

Abstract Foundation pit excavation through the soft layer has great technical challenges and potential safety risks, especially in soft soil area. In this study, we use a 3D numerical model of Foundation pit to simulate the excavation process. Based on the simulation, the sensitivity analysis of the three stiffness parameters ( $${\mathrm{E}}_{\mathrm{ur}}^{\mathrm{ref}}$$ E ur ref , $${\mathrm{E}}_{50}^{\mathrm{ref}}$$ E 50 ref and $${\mathrm{E}}_{\mathrm{oed}}^{\mathrm{ref}}$$ E oed ref ) of the Modified Mohr–Coulomb model was carried out by using the Latin hypercube-one factor at a time method. During the simulation, the three stiffness parameters are changed with the perturbation amplitude of (± 20%) and (± 40%). In addition, the sensitivity of three stiffness parameters was calculated by taking the horizontal displacement of diaphragm wall as the observation index. Furthermore, by comparing the results of simulation with the measured data, the stiffness ratio relationship suitable for foundation pit simulation in Tianjin water-rich soft soil area are obtained. Our findings present that $${\mathrm{E}}_{\mathrm{ur}}^{\mathrm{ref}}$$ E ur ref is the parameter that has the largest influence on the uncertainty in the MMC model, while $${\mathrm{E}}_{\mathrm{oed}}^{\mathrm{ref}}$$ E oed ref is the least sensitive to horizontal displacement of diaphragm wall. The proportion rates of $${\mathrm{E}}_{\mathrm{oed}}^{\mathrm{ref}}$$ E oed ref / $${\mathrm{E}}_{50}^{\mathrm{ref}}$$ E 50 ref and $${\mathrm{E}}_{\mathrm{ur}}^{\mathrm{ref}}{/\mathrm{E}}_{50}^{\mathrm{ref}}$$ E ur ref / E 50 ref provide a promising reference for simulating the foundation pit excavation in Tianjin water-rich soft soil area.

Objectives This study aims to investigate the incidence of and factors associated with irritable bowel syndrome (IBS) among resident physicians in standardised training at eight traditional Chinese medicine (TCM) hospitals in China.Design A cross-sectional survey was administered to resident physicians in their first to third years of standardised training at eight TCM hospitals.Participants and setting A total of 514 resident physicians in standardised training were included.Measures The questionnaire consisted of two sections, namely: section A collected basic information, and section B included the four-item Perceived Stress Scale (PSS-4), the Patient Health Questionnaire-4 (PHQ-4), the Pittsburgh Sleep Quality Index (PSQI) and the Rome IV criteria for IBS. Univariate and multivariate logistic regression models were constructed to assess the associations of age, sex, body mass index, stress, depression, anxiety, sleep quality and IBS.Results Of the included resident doctors, 77.2% were female, 20.4% were obese or underweight and 8.6% had symptoms consistent with a diagnosis of IBS. There were no statistically significant differences in lifestyle factors (night shift work, overtime work or working efficiency during the COVID-19 pandemic) between patients with IBS and participants without IBS (hereafter, non-IBS participants) (p=0.429, p=0.572 or p=0.464, respectively). Notably, compared with non-IBS participants, patients with IBS had significantly higher mean scores on the PSS-4 and PHQ-4 (p=0.028 and p=0.012, respectively); however, there was not a significant difference in PSQI scores between these two groups (p=0.079). Depression symptoms were significantly associated with IBS (unadjusted OR 0.498, 95% CI 0.265 to 0.935, p=0.030).Conclusion These findings suggest that IBS is common among resident physicians in standardised training. Future studies should investigate emotional distress, especially stress and depression, in the development of prevention or treatment of IBS.

Meat yield, determined by muscle growth and development, is an important economic trait for the swine industry and a focus of research in animal genetics and breeding. PDZ and LIM domain 5 (PDLIM5) are cytoskeleton-related proteins that play key roles in various tissues and cells. These proteins have multiple isoforms, primarily categorized as short (PDLIM5-short) and long (PDLIM5-long) types, distinguished by the absence and presence of an LIM domain, respectively. However, the expression patterns of swine PDLIM5 isoforms and their regulation during porcine skeletal muscle development remain largely unexplored. We observed that PDLIM5-long was expressed at very low levels in pig muscles and that PDLIM5-short and total PDLIM5 were highly expressed in the muscles of slow-growing pigs, suggesting that PDLIM5-short, the dominant transcript in pigs, is associated with a slow rate of muscle growth. PDLIM5-short suppressed myoblast proliferation and myogenic differentiation in vitro. We also identified two single nucleotide polymorphisms (−258 A > T and −191 T > G) in the 5′ flanking region of PDLIM5, which influenced the activity of the promoter and were associated with muscle growth rate in pigs. In summary, we demonstrated that PDLIM5-short negatively regulates myoblast proliferation and differentiation, providing a theoretical basis for improving pig breeding programs.

Abstract Many previous studies have documented the relationship between the North Pacific Oscillation (NPO) and the weather/climate of upstream and downstream regions. However, the stability of NPO precursor signals of East Asian summer precipitation, which is important for climate prediction, has received little attention. This study identified temporal variations in the connection between the May NPO and subsequent midsummer precipitation over Northeast China (NEC) during 1961–2020. During 1986–2010, the correlation between the May NPO and midsummer precipitation over NEC was found significantly positive, whereas the relation was found statistically insignificant during 1961–1985/2011–2020. Further results indicated that the NPO stimulated a Rossby wave source over the North Pacific that was stronger during 1986–2010 than during 1961–1985/2011–2020. The Rossby wave source anomalies shifted to North America and to the North Atlantic during the subsequent June and midsummer, respectively. Consequently, a teleconnection wave train, which originated over the North Pacific, propagated eastward to North America, across the North Atlantic, and on to East Asia on the subseasonal time scale, influencing midsummer precipitation over NEC through modulation of the atmospheric circulation (e.g., horizontal wind, moisture transport, and vertical movement). Moreover, the intensified Rossby wave anomalies associated with the May NPO were attributed to the strengthened NPO, which could be related to the enhanced standard deviation of SLP over the North Pacific. Additionally, the strengthened out‐of‐phase relation between the NPO and the North Atlantic Oscillation, resulting from changes in the background circulation, partially contributed to intensification of the Rossby wave train.

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

Global patterns in clutch size variations across species have been linked to resource availability and seasonal climate change. However, our understanding of the specific local-scale drivers of clutch size diversity has remained unclear, especially among populations of ectotherms with relatively homogeneous genetic structures experiencing varying local environmental conditions. And understanding the specific local-scale drivers of clutch size diversity within species can provide insight into the local adaptation of species or the evolution of key life history traits. Here, we collected clutch size data of a wide-ranging female lizard (Eremias argus) from field observation and literature across populations of varying elevations and latitudes in China. We then used mixed-effects models to test the relationship between clutch size, body size, habitat type, elevation, latitudes, and climate conditions. Unsurprisingly, body size was positively correlated with clutch size variations across all populations. When we accounted for body size, females from populations at higher latitudes had larger clutches, while females in less variable rainfall environments had smaller clutches. Interestingly, we found that females occupying higher geographic gradients (e.g., latitude and elevation) with certain habitats (e.g., grasslands and farmlands) were associated with larger clutch sizes. Thus, our study shows support for similar global macroecological drivers of clutch size diversity among lizard species, and also suggests that female ectotherms might have different reproductive decisions employed in response to local climates to maximise population replacement.

Objective: Shengmai injection is a common treatment for coronary heart disease. The accurate dose regimen is important to maximize effectiveness and minimize adverse reactions. We aim to explore the effect of Shengmai injection in patients with coronary heart disease based on real-world data and establish a personalized medicine model using machine learning and deep learning techniques.Methods: 211 patients were enrolled. The length of hospital stay was used to explore the effect of Shengmai injection in a case-control study. We applied propensity score matching to reduce bias and Wilcoxon rank sum test to compare results between the experimental group and the control group. Important variables influencing the dose regimen of Shengmai injection were screened by XGBoost. A personalized medicine model of Shengmai injection was established by XGBoost selected from nine algorithm models. SHapley Additive exPlanations and confusion matrix were used to interpret the results clinically.Results: Patients using Shengmai injection had shorter length of hospital stay than those not using Shengmai injection (median 10.00 days vs. 11.00 days, p = 0.006). The personalized medicine model established via XGBoost shows accuracy = 0.81 and AUC = 0.87 in test cohort and accuracy = 0.84 and AUC = 0.84 in external verification. The important variables influencing the dose regimen of Shengmai injection include lipid-lowering drugs, platelet-lowering drugs, levels of GGT, hemoglobin, prealbumin, and cholesterol at admission. Finally, the personalized model shows precision = 75%, recall rate = 83% and F1-score = 79% for predicting 40 mg of Shengmai injection; and precision = 86%, recall rate = 79% and F1-score = 83% for predicting 60 mg of Shengmai injection.Conclusion: This study provides evidence supporting the clinical effectiveness of Shengmai injection, and established its personalized medicine model, which may help clinicians make better decisions.

Abstract Background Trametes gibbosa, which is a white-rot fungus of the Polyporaceae family found in the cold temperate zone, causes spongy white rot on wood. Laccase can oxidize benzene homologs and is one of the important oxidases for white rot fungi to degrade wood. However, the pathway of laccase synthesis in white rot fungi is unknown. Results The peak value of laccase activity reached 135.75 U/min/L on the 9th day. For laccase activity and RNA-seq data, gene expression was segmented into 24 modules. Turquoise and blue modules had greater associations with laccase activity (positively 0.94 and negatively -0.86, respectively). For biology function, these genes were concentrated on the cell cycle, citrate cycle, nicotinate, and nicotinamide metabolism, succinate dehydrogenase activity, flavin adenine dinucleotide binding, and oxidoreductase activity which are highly related to the laccase synthetic pathway. Among them, gene_8826 (MW199767), gene_7458 (MW199766), gene_61 (MW199765), gene_1741 (MH257605), and gene_11087 (MK805159) were identified as central genes. Conclusion Laccase activity steadily increased in wood degradation. Laccase oxidation consumes oxygen to produce hydrogen ions and water during the degradation of wood. Some of the hydrogen ions produced can be combined by Flavin adenine dinucleotide (FAD) to form reduced Flavin dinucleotide (FADH2), which can be transmitted. Also, the fungus was starved of oxygen throughout fermentation, and the NADH and FADH2 are unable to transfer hydrogen under hypoxia, resulting in the inability of NAD and FAD to regenerate and inhibit the tricarboxylic acid cycle of cells. These key hub genes related to laccase activity play important roles in the molecular mechanisms of laccase synthesis for exploring industrial excellent strains.

(1) Background: It is well-known that long non-coding RNAs (lncRNAs) and N7-methylguanosine (m7G) contribute to hepatocellular carcinoma (HCC) progression. However, it remains unclear whether lncRNAs regulating m7G modification could predict HCC prognosis. Thus, we sought to explore the prognostic implications of m7G-related lncRNAs in HCC patients. (2) Methods: Prognostic M7G-related lncRNAs obtained from The Cancer Genome Atlas (TCGA) database were screened by co-expression analysis and univariate Cox regression analysis. Next, the m7G-related lncRNA signature (m7GRLSig) was conducted by Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analysis. Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC) assessed the prognostic abilities of our signature. Univariate and multivariate Cox regression, nomogram, and principal component analysis (PCA) were conducted to evaluate our signature. Subsequently, we investigated the role of m7GRLSig on the immune landscape and sensitivity to drugs in HCC patients. The potential function of lncRNAs obtained from the prognostic signature was explored by in vitro experiments. (3) Results: A novel m7GRLSig was identified using seven meaningful lncRNA (ZFPM2-AS1, AC092171.2, PIK3CD-AS2, NRAV, CASC19, HPN-AS1, AC022613.1). The m7GLPSig exhibited worse survival in the high-risk group and served as an independent prognostic factor. The m7GRLSig stratification was sensitive in assessing the immune landscape and sensitivity to drugs between the high-risk and low-risk groups. Finally, in vitro experiments confirmed that the knockdown of NRAV was accompanied by the downregulation of METTL1 during HCC progression. (4) Conclusions: The m7G-related signature is a potential predictor of HCC prognosis and contributes to individualize the effective drug treatment of HCC.

Abstract We find a near detailed balance solution to the relativistic Boltzmann equation under the relaxation time approximation with a collision term which differs from the Anderson–Witting model and is dependent on the stationary observer. Using this new solution, we construct an explicit covariant transport equation for the particle flux in response to the generalized temperature and chemical potential gradients in generic stationary spacetimes, with the transport tensors characterized by some integral functions in the chemical potential and the relativistic coldness. To illustrate the application of the transport equation, we study probe systems in Rindler and Kerr spacetimes and analyze the asymptotic properties of the gravito-conductivity tensor in the near horizon limit. It turns out that both the longitudinal and lateral parts (if present) of the gravito-conductivity tend to be divergent in the near horizon limit. In the weak field limit, our results coincide with the non-relativistic gravitational transport equation which follows from the direct application of the Drude model.

IntroductionThe leaf-chewing pest Heortia vitessoides severely threatens the growth and development of Aquilaria sinensis. In our previous study, we found that mechanical damage (MD) to stem enhanced A. sinensis sapling resistance to H. vitessoides larvae.MethodsTo reveal the defense mechanisms underlying this observation, we analyzed the types and contents of volatile organic compounds (VOCs), phytohormone contents, and expression of phytohormone-related genes in response to MD and herbivory wounding(HW).ResultsHere, we identified several VOCs, such as the pesticides fenobucarb and 2,4-di-tert-butylphenol, in mature leaf (ML) of MD-treated plants. Compared with salicylic acid (SA) or the ethylene (ET) pathway, jasmonic acid (JA) content and JA-related genes were more strongly upregulated. Interestingly, we found a dramatic difference between JA-related upstream and downstream genes expression in YL and ML, which confirmed that JA-Ile accumulation in MD-ML and HW-ML could be derived from local damaged site.DiscussionTaken together, we provide evidence that the JA pathway plays a dominant role in the A. sinensis response to MD and HW.

Abstract Background Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality, feed utilization, and reproduction. Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes, which involves a cascade of regulatory molecules. Accumulating evidence has shown that microRNAs (miRNAs) serve as post-transcriptional regulators of adipogenic differentiation in mammals. However, the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood. This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis. Results We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation (0, 12, 48, 72, and 120 h). A total of 217 differentially expressed miRNAs (DE-miRNAs) and 3520 differentially expressed genes were identified. Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways, including the PPAR signaling and MAPK signaling pathways. A candidate miRNA, gga-miR-106-5p, exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens. gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. A dual-luciferase reporter assay suggested that the KLF15 gene, which encodes a transcriptional factor, is a direct target of gga-miR-106-5p. gga-miR-106-5p suppressed the post-transcriptional activity of KLF15, which is an activator of abdominal preadipocyte proliferation and differentiation, as determined with gain- and loss-of-function experiments. Conclusions gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens. These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.

Abstract Transmembrane-4 L-six family member-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate tumor cell behaviors. However, the function and mechanism of TM4SF1 in esophageal squamous cell carcinoma (ESCC) metastasis remains unclear. Here, we find that TM4SF1 expression is increased and positively correlated with clinical TNM stage, N classification, differentiation, tumor size, and poor prognosis in ESCC patients. Interestingly, we demonstrate that TM4SF1 promotes ESCC cell adhesion, spreading, migration, and invasion, but not cell proliferation, in a laminin-dependent manner by interacting with integrin α6. Mechanistically, the TM4SF1/integrin α6/FAK axis signal pathway mediates cell migration under laminin-coating condition. Inhibiting FAK or knocking down TM4SF1 can attenuate TM4SF1-mediated cell migration and lung metastasis. Clinically, the TM4SF1/integrin α6/FAK axis positively correlates with ESCC. Altogether, these findings reveal a new mechanism of TM4SF1 in promoting ESCC metastasis via binding to integrin α6 and suggest that the cross-talk between TM4SF1 and integrin α6 may serve as a therapeutic target for ESCC.

Abstract Pine wilt disease (PWD) is a worldwide forest disease caused by pine wood nematode (PWN). In this article, we investigated the composition, organization, correlation, and function of the endophytic microbial community in Pinus massoniana field with and without PWN. Samples were taken from branches, upper, middle, and lower trunks, as well as soil, from both healthy and infected trees. The results showed that the fungal diversity of healthy pines is around 1.1 times that of infected pines, while the bacterial diversity is about 0.75 times that of infected pines at the OTUs level. An increase of the abundance of pathogenic fungus such as Saitozyma, Graphilbum, Diplodia, Candida, Pseudoxanthomonas, Dyella and Pantoea was witnessed in infected pines according to the result of LEfSe. Furthermore, Ophiostoma and saprophytic fungus such as Entomocorticium, ganoderma, tomentella, entomocorticium were exclusively prominent in infected pines, which were substantially and highly connected with other species (p

Autism spectrum disorder (ASD) is associated with severe impairment in social functioning. Visual information processing provides nonverbal cues that support social interactions. ASD children exhibit abnormalities in visual orientation, continuous visual exploration, and visual–spatial perception, causing social dysfunction, and mechanisms underlying these abnormalities remain unclear. Transmission of visual information depends on the retina-lateral geniculate nucleus–visual cortex pathway. In ASD, developmental abnormalities occur in rapid expansion of the visual cortex surface area with constant thickness during early life, causing abnormal transmission of the peak of the visual evoked potential (P100). We hypothesized that abnormal visual perception in ASD are related to the abnormal visual information transmission and abnormal development of visual cortex in early life, what’s more, explored the mechanisms of abnormal visual symptoms to provide suggestions for future research.

In the summer of 2020, China experienced record rainfall and flooding. Here, the authors investigate the connection between the rainfall and the abrupt decrease in emissions due to Covid-19 and find that the emission decrease may have contributed to the rainfall.

In hybrid plasmonic Si waveguides integrated with ultrathin Au stripes, mode hybridization effects between quasi-TE modes of different orders and various bound modes are first presented. Enabled by nearly complete mode-selective absorption attributed to the enlarged mode propagation attenuation (MPA) coefficient for lower-order quasi-TE modes under circumstances of mode hybridizations, multi-segment tapered structures are theoretically proposed to constitute high order mode (HOM) pass filters. It is believed that these innovative observations would have potential applications in the ultra-compact on-chip mode division multiplexing (MDM) systems, and provide inspirations for the development of multimode photonics.

Humans can flexibly represent both categorical and coordinate spatial relations. Previous research has mainly focused on hemisphere lateralization in representing these two types of spatial relations, but little is known about how distinct network organization states support representations of the two. Here we used dynamic resting-state functional connectivity (FC) to explore this question. To do this, we separated a meta-identified navigation network into a ventral and two other subnetworks. We revealed a Weak State and a Strong State within the ventral subnetwork and a Negative State and a Positive State between the ventral and other subnetworks. Further, we found the Weak State (i.e., weak but positive FC) within the ventral subnetwork was related to the ability of categorical relation recognition, suggesting that the representation of categorical spatial relations was related to weak integration among focal regions in the navigation network. In contrast, the Negative State (i.e., negative FC) between the ventral and other subnetworks was associated with the ability of coordinate relation processing, suggesting that the representation of coordinate spatial relations may require competitive interactions among widely distributed regions. In sum, our study provides the first empirical evidence revealing different focal and distributed organizations of the navigation network in representing different types of spatial information.

Valproic acid/sodium valproate (VPA) is a widely used anticonvulsant drug for maintenance treatment of bipolar disorders. In order to balance the efficacy and adverse events of VPA treatment, an individualized dose regimen is necessary. This study aimed to establish an individualized medication model of VPA for patients with bipolar disorder based on machine learning and deep learning techniques. The sequential forward selection (SFS) algorithm was applied for selecting a feature subset, and random forest was used for interpolating missing values. Then, we compared nine models using XGBoost, LightGBM, CatBoost, random forest, GBDT, SVM, logistic regression, ANN, and TabNet, and CatBoost was chosen to establish the individualized medication model with the best performance (accuracy = 0.85, AUC = 0.91, sensitivity = 0.85, and specificity = 0.83). Three important variables that correlated with VPA daily dose included VPA TDM value, antipsychotics, and indirect bilirubin. SHapley Additive exPlanations was applied to visually interpret their impacts on VPA daily dose. Last, the confusion matrix presented that predicting a daily dose of 0.5 g VPA had a precision of 55.56% and recall rate of 83.33%, and predicting a daily dose of 1 g VPA had a precision of 95.83% and a recall rate of 85.19%. In conclusion, the individualized medication model of VPA for patients with bipolar disorder based on CatBoost had a good prediction ability, which provides guidance for clinicians to propose the optimal medication regimen.

BackgroundBlood-brain barrier (BBB) disruption and gut microbiota dysbiosis play crucial roles in Alzheimer’s disease (AD). Lipopolysaccharide (LPS) stimulation triggered by gut microbial dysbiosis is an important factor in BBB disruption and systemic inflammation, but the mechanism of acupuncture regulation of BBB disruption via the gut microbiota in AD is not clear.ObjectiveThe current study evaluated the effect of manual acupuncture (MA) on BBB dysfunction in APP/PS1 mice and examined the mechanism of gut microbiota by acupuncture in AD.MethodsAcupoints were applied to Baihui (GV20), Yintang (GV29), and Zusanli (ST36) in the MA group. Mice in the manual acupuncture plus antibiotics (MAa) group received antibiotics and acupuncture, while mice in the probiotics (P) group received probiotics. Alterations in spatial learning and memory, the gut microbiota, tightly connected structure and permeability of BBB, and the expression of LPS and inflammatory factors in each group were assessed.ResultsCompared to the normal (N) group, cognitive ability was significantly impaired, the gut microbiota composition was markedly altered, the BBB was significantly disrupted, and the expression of LPS in serum and brain, serum TNF-α, and IL-1β were significantly increased in the AD group (p < 0.01). These changes were inhibited in the MA and P groups (p < 0.01 or p < 0.05), and antibiotics reversed the benign regulatory effects of MA (p < 0.01 or p < 0.05).ConclusionManual acupuncture benignly modulated the gut microbiota and BBB dysfunction, reduced LPS, TNF-α, and IL-1β. These effects were comparable to probiotics. The decrease in LPS load and systemic inflammation may play important roles in the regulation of BBB dysfunction by acupuncture, and the gut microbiota may be a potential target for the benign regulation of BBB disruption by acupuncture.

Magnetism in two-dimensional (2D) materials has attracted much attention recently. However, intrinsic magnetic 2D materials are rare and mostly unstable in ambient. Although heteroatom doping can introduce magnetism, the basic property especially the electrical-magnetic coupling property has been rarely revealed. Herein, both iron (Fe)-doped and vanadium (V)-doped MoS2 films were grown by chemical vapor deposition. Through studying the structure and electrical property of Fe-doped and V-doped MoS2, it was found that both Fe and V doping would decrease the electron concentration, exhibiting a p-type doping effect. Significantly, V-doped MoS2 displays a p-type conduction behavior. Although the carrier mobility decreases after heteroatom doping, both Fe and V doping could endow MoS2 with magnetism, in which the transfer curves of both MoS2 transistors exhibit a strong magnetic-dependent behavior. It is found that the magnetic response of Fe-doped MoS2 can be tuned from ~0.2 ​nA/T to ~1.3 ​nA/T, with the tunability much larger than that of V-doped MoS2. At last, the magnetic mechanism is discussed with the local magnetic property performed by magnetic force microscopy. The typical morphology-independent magnetic signal demonstrates the formed magnetic domain structure in Fe-doped MoS2. This study opens new potential to design novel magnetic-electrical devices.

Bacterial biofilms pose a serious threat to human health, as they prevent the penetration of antimicrobial agents. Developing nanocarriers that can simultaneously permeate biofilms and deliver antibacterial agents is an attractive means of treating bacterial biofilm infections. Herein, photosensitive metal–organic framework (MOF) nanoparticles were developed to promote the penetration of antibiotics into biofilms, thereby achieving the goal of eradicating bacterial biofilms through synergistic photodynamic and antibiotic therapy. First, a ligand containing benzoselenadiazole was synthesized and incorporated into MOF skeletons to construct benzoselenadiazole-doped MOFs (Se-MOFs). The growth of the Se-MOFs could be regulated to obtain nanoparticles (Se-NPs) in the presence of benzoic acid. The singlet oxygen (1O2) generation efficiencies of the Se-MOFs and Se-NPs were evaluated. The results show that the Se-NPs exhibited a higher 1O2 generation efficacy than the Se-MOF under visible-light irradiation because the small size of the Se-NPs was conducive to the diffusion of 1O2. Afterward, an antibiotic drug, polymyxin B (PMB), was conjugated onto the surface of the Se-NPs via amidation to yield PMB-modified Se-NPs (PMB-Se-NPs). PMB-Se-NPs exhibit a synergistic antibacterial effect by specifically targeting the lipopolysaccharides present in the outer membranes of Gram-negative bacteria through surface-modified PMB. Benefiting from the synergistic therapeutic effects of antibiotic and photodynamic therapy, PMB-Se-NPs can efficiently eradicate bacterial biofilms at relatively low antibiotic doses and light intensities, providing a promising nanocomposite for combating biofilm infections.

BackgroundGut microbiota dysbiosis and intestinal barrier injury play vital roles in Alzheimer’s disease (AD) onset and development. Our previous studies have demonstrated that manual acupuncture (MA) could improve the cognitive abilities of APP/PS1 mice. However, the effect of MA on the intestinal mucosal barrier and the gut microbiota mechanism through which this effect occurs remain to be clarified.MethodsIn the APP/PS1 manual acupuncture (Am) group, MA was applied in Baihui (GV20), Yintang (GV29), and Zusanli (ST36). Mice in the APP/PS1 antibiotic + manual acupuncture (Aa) group were treated with an antibiotic mixture and MA at the same time. Probiotics were delivered to the APP/PS1 probiotics (Ap) group. Alterations in spatial learning and memory, the gut microbiota, the intestinal barrier function, and the expression of glial fibrillary acidic protein (GFAP), lipopolysaccharide (LPS), and TNF-α were evaluated in each group.ResultsCompared with the C57BL/6 control (Cc) group, cognitive ability was significantly decreased, the gut microbiota structure was obviously disrupted, intestinal barrier integrity was drastically impaired, and the intestinal inflammatory response was enhanced in the APP/PS1 control (Ac) group (P < 0.01). These changes were reversed by MA and probiotics (P < 0.01 or P < 0.05), whereas antibiotics inhibited the benign regulation by MA (P < 0.01 or P < 0.05).ConclusionManual acupuncture can benignly modulate gut microbiota dysbiosis, significantly reduce intestinal inflammation, and effectively alleviate the destruction of the intestinal mucosal barrier in APP/PS1 mice, and the effects are comparable to those of probiotics. The gut microbiota may play an important role in the improvement of the cognitive function and intestinal barrier function by MA.

Lapatinib is used for the treatment of metastatic HER2(+) breast cancer. We aim to establish a prediction model for lapatinib dose using machine learning and deep learning techniques based on a real-world study. There were 149 breast cancer patients enrolled from July 2016 to June 2017 at Fudan University Shanghai Cancer Center. The sequential forward selection algorithm based on random forest was applied for variable selection. Twelve machine learning and deep learning algorithms were compared in terms of their predictive abilities (logistic regression, SVM, random forest, Adaboost, XGBoost, GBDT, LightGBM, CatBoost, TabNet, ANN, Super TML, and Wide&Deep). As a result, TabNet was chosen to construct the prediction model with the best performance (accuracy = 0.82 and AUC = 0.83). Afterward, four variables that strongly correlated with lapatinib dose were ranked via importance score as follows: treatment protocols, weight, number of chemotherapy treatments, and number of metastases. Finally, the confusion matrix was used to validate the model for a dose regimen of 1,250 mg lapatinib (precision = 81% and recall = 95%), and for a dose regimen of 1,000 mg lapatinib (precision = 87% and recall = 64%). To conclude, we established a deep learning model to predict lapatinib dose based on important influencing variables selected from real-world evidence, to achieve an optimal individualized dose regimen with good predictive performance.

Abstract Background TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of breast cancer. There is an urgent need for identification of therapeutic agents with unique mode of action for overcoming current challenges in TNBC treatment. Methods Different inhibitors were used to study the cell death manner of DMOCPTL. RNA silencing was used to evaluate the functions of GPX4 in ferroptosis and apoptosis of TNBC cells and functions of EGR1 in apoptosis. Immunohistochemical assay of tissue microarray were used for investigating correlation of GPX4 and EGR1 with TNBC. Computer-aided docking and small molecule probe were used for study the binding of DMOCPTL with GPX4. Results DMOCPTL, a derivative of natural product parthenolide, exhibited about 15-fold improvement comparing to that of the parent compound PTL for TNBC cells. The cell death manner assay showed that the anti-TNBC effect of DMOCPTL mainly by inducing ferroptosis and apoptosis through ubiquitination of GPX4. The probe of DMOCPTL assay indicated that DMOCPTL induced GPX4 ubiquitination by directly binding to GPX4 protein. To the best of our knowledge, this is the first report of inducing ferroptosis through ubiquitination of GPX4. Moreover, the mechanism of GPX4 regulation of apoptosis is still obscure. Here, we firstly reveal that GPX4 regulated mitochondria-mediated apoptosis through regulation of EGR1 in TNBC cells. Compound 13, the prodrug of DMOCPTL, effectively inhibited the growth of breast tumor and prolonged the lifespan of mice in vivo, and no obvious toxicity was observed. Conclusions These findings firstly revealed novel manner to induce ferroptosis through ubiquitination of GPX4 and provided mechanism for GPX4 inducing mitochondria-mediated apoptosis through up-regulation of EGR1 in TNBC cells. Moreover, compound 13 deserves further studies as a lead compound with novel mode of action for ultimate discovery of effective anti-TNBC drug.

Tacrolimus is a major immunosuppressor against post-transplant rejection in kidney transplant recipients. However, the narrow therapeutic index of tacrolimus and considerable variability among individuals are challenges for therapeutic outcomes. The aim of this study was to compare different machine learning and deep learning algorithms and establish individualized dose prediction models by using the best performing algorithm. Therefore, among the 10 commonly used algorithms we compared, the TabNet algorithm outperformed other algorithms with the highest R2 (0.824), the lowest prediction error [mean absolute error (MAE) 0.468, mean square error (MSE) 0.558, and root mean square error (RMSE) 0.745], and good performance of overestimated (5.29%) or underestimated dose percentage (8.52%). In the final prediction model, the last tacrolimus daily dose, the last tacrolimus therapeutic drug monitoring value, time after transplantation, hematocrit, serum creatinine, aspartate aminotransferase, weight, CYP3A5, body mass index, and uric acid were the most influential variables on tacrolimus daily dose. Our study provides a reference for the application of deep learning technique in tacrolimus dose estimation, and the TabNet model with desirable predictive performance is expected to be expanded and applied in future clinical practice.

Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs.Methods: This is a “three-phase” study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ2 test, and Mann–Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation.Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost (p < 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p < 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver.Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.

Pinewood nematode (PWN; Bursaphelenchus xylophilus) is a devastating invasive species that is expanding into colder regions. Here, we investigated the molecular mechanisms underlying low‐temperature resistance of PWN. We identified differentially expressed genes enriched under low temperature in previously published transcriptome data using the Kyoto Encyclopedia of Genes and Genomes. Quantitative real‐time PCR was used to further validate the transcript level changes of three known cytochrome P450 genes under low temperature. RNA interference was used to validate the low‐temperature resistance function of three cytochrome P450 genes from PWN. We report that differentially expressed genes were significantly enriched in two cytochrome P450‐related pathways under low‐temperature treatment. Heatmap visualization of transcript levels of cytochrome P450‐related genes revealed widely different transcript patterns between PWNs treated under low and regular temperatures. Transcript levels of three cytochrome P450 genes from PWNs were elevated at low temperature, and knockdown of these genes decreased the survival rates of PWNs under low temperature. In summary, these findings suggest that cytochrome P450 metabolism plays a critical role in the low‐temperature resistance mechanism of PWN.

Abstract Myeloid-derived suppressor cells (MDSCs) are notable contributors to the immunosuppressive tumor microenvironment (TME) and are closely associated with tumor progression; in addition, MDSCs are present in most patients with cancer. However, the molecular mechanisms that regulate MDSCs in the etiopathogenesis of human tumor immunity remain unclear. The secreted alarmin high mobility group box 1 (HMGB1) is a proinflammatory factor and inducer of many inflammatory molecules during MDSC development. In this review, we detail the currently reported characteristics of MDSCs in tumor immune escape and the regulatory role of secreted HMGB1 in MDSC differentiation, proliferation, activity and survival. Notably, different posttranslational modifications of HMGB1 may have various effects on MDSCs, and these effects need further identification. Moreover, exosome-derived HMGB1 is speculated to exert a regulatory effect on MDSCs, but no report has confirmed this hypothesis. Therefore, the effects of HMGB1 on MDSCs need more research attention, and additional investigations should be conducted.

EVOH-SO3Li/P(VDF-HFP)/HAP lithium ion battery separator was prepared by high-pressure blending electrospinning using polyethylene-vinyl alcohol sulfonate (EVOH-SO3Li), poly(vinylidene fluoride-hexafluoropropylene) (P(VDF-HFP)) and nano hydroxyapatite (HAP) as raw materials. The performance of the separator was characterized by FTIR, SEM, electrochemical workstation and battery detection system. The results show that the EVOH-SO3Li/P(VDF-HFP) composite separator forms an uniform and dense three-dimensional network structure, and the EVOH-SO3Li/P(VDF-HFP)/HAP composite separator presents a three-dimensional network of dendritic shapes after adding P(VDF-HFP) and HAP, which improves the porosity and liquid absorption rate of the separator. Compared with the pure EVOH-SO3Li separator, the porosity and liquid absorption rate of the EVOH-SO3Li/P(VDF-HFP)/HAP composite separator are increased by 37.5% and 91.6%, respectively. Meanwhile, the excellent electrochemical performance is also exhibited. The electrochemical stability window of the assembled lithium-ion battery is 5.65 V, and the interfacial impedance is decreased to 184.24 Ω, and the ionic conductivity is increased to 2.686×10-3 S·cm-1; Lithium-ion batteries assembled with EVOH-SO3Li/P(VDF-HFP)/HAP composite separator have a capacity retention rate of 96.69% after 100 cycles at 0.5 C discharge current, the properties of EVOH-SO3Li/P(VDF-HFP)/HAP composite separator are improved compared with EVOH-SO3Li.

Bursaphelenchus xylophilus causes pine wilt disease, which poses a serious threat to forestry ecology around the world. Microorganisms are environmentally friendly alternatives to the use of chemical nematicides to control B. xylophilus in a sustainable way. In this study, we isolated a nematophagous fungus—Arthrobotrys robusta—from the xylem of diseased Pinus massoniana. The nematophagous activity of A. robusta against the PWNs was observed after just 6 h. We found that B. xylophilus entered the trap of A. robusta at 24 h, and the nervous system and immunological response of B. xylophilus were stimulated by metabolites that A. robusta produced. At 30 h of exposure to A. robusta, B. xylophilus exhibited significant constriction, and we were able to identify xenobiotics. Bursaphelenchus xylophilus activated xenobiotic metabolism, which expelled the xenobiotics from their bodies, by providing energy through lipid metabolism. When PWNs were exposed to A. robusta for 36 h, lysosomal and autophagy-related genes were activated, and the bodies of the nematodes underwent disintegration. Moreover, a gene co-expression pattern network was constructed by WGCNA and Cytoscape. The gene co-expression pattern network suggested that metabolic processes, developmental processes, detoxification, biological regulation, and signaling were influential when the B. xylophilus specimens were exposed to A. robusta. Additionally, bZIP transcription factors, ankyrin, ATPases, innexin, major facilitator, and cytochrome P450 played critical roles in the network. This study proposes a model in which mobility improved whenever B. xylophilus entered the traps of A. robusta. The model will provide a solid foundation with which to understand the molecular and evolutionary mechanisms underlying interactions between nematodes and nematophagous fungi. Taken together, these findings contribute in several ways to our understanding of B. xylophilus exposed to microorganisms and provide a basis for establishing an environmentally friendly prevention and control strategy.

Central heating in North China produces severe air pollution, although the need for heating may be reduced by rising temperatures associated with climate change. The regional trend of mean heating length (HL) for North China was −0.32 d per year during 1961–2019. Compared with the 2010–2015 mean values, the start and end dates for central heating in the North China Plain (NCP) during 2050–2055 will delayed by 9 d and advanced by 12 d, respectively, under the Shared Socioeconomic Pathway 5–8.5 (SSP5-85), and by 5 and 8 d under the carbon-neutral (CN) scenario, based on Coupled Model Intercomparison Project phase 6 model simulations. Here we propose a flexible heating policy (FHP), such that HL is determined strictly by temperature, and the associated air pollution benefit of shortening HL are examined by a global 3D chemical transport model GEOS-Chem. The study focused on the year 2019 with the current goal of elimination of severe PM _2.5 pollution, and with the minimum HL estimated to provide up to a 24% reduction in severe PM _2.5 pollution (daily mean PM _2.5 > 150 μ g m ^−3 ) over the NCP during periods of FHP implementation. For future CN policies, the NCP can achieve great air quality improvements by 2050, with more than 60% of days throughout the heating season with daily PM _2.5 concentrations of 100 μ g m ^−3 still occurring frequently by 2050. Our results highlight that FHPs may effectively reduce severe PM _2.5 pollution, and China’s carbon neutrality goals will play critical roles in mitigating air pollution and prolonged heating welfare during future heating season.