Search

Abstract Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan–Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.

Abstract All-solid-state batteries with non-flammable solid electrolytes offer enhanced safety features, and show the potential for achieving higher energy density by using lithium metal as the anode. Among various solid electrolytes, sulfides are favored for their high room-temperature ionic conductivity and low-temperature processing. However, making large-scale thin electrolyte films via pressing sulfide powder is still challenging. A polymer has recently been introduced as a binder or framework to obtain a flexible thin sulfide-based composite electrolyte film with high ionic conductivity. In this Review, we initially discuss the ionic transport mechanism of sulfide/polymer composite electrolyte films. Then, the preparation methods and the properties of sulfide-based composite electrolytes are introduced in detail, and the advantages and disadvantages of each method are also analyzed. We later discuss the application of composite electrolyte films in all-solid-state batteries. Finally, we provide a perspective on the future development direction of sulfide-based composite electrolyte films.

Abstract Background The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. Methods Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. Conclusions Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. Trial registration ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

Objective To study the changes of protein levels in peripheral blood after it dried. Methods The proteins from whole blood and bloodstains were detected by liquid chromatography-tandem mass spectrometry （LC-MS/MS） and normalized by the label-free quantification （LFQ） method. The differential proteins were analyzed by using R 4.2.1 software, limma and edgeR package. The analysis of biological function, signaling pathway and subcellular localization for the differential proteins was then performed. Results A total of 623 and 596 proteins were detected in whole blood and bloodstains, respectively, of which 31 were statistically significant in the quantitative results, including 10 up-regulated and 21 down-regulated proteins in bloodstains. Conclusion The protein abundances in whole blood and bloodstains are highly correlated, and the variation of protein abundances may be related to the changes of endogenous and structural proteins in cells. The application of proteomics technology can assist the screening and identification of protein biomarkers, thereby introducing new biomarkers for forensic research.

Improving soil quality while achieving higher productivity is the major challenge in the agricultural industry. Wheat (Triticum aestivum L.)–maize (Zea mays L.) (W–M) rotation is the dominant planting pattern in the Huang-Huai-Hai Plain and is important for food security in China. However, the soil quality is deteriorating due to the W–M rotation's long-term, intensive, and continuous cultivation. Introducing legumes into the W–M rotation system may be an effective way to improve soil quality. In this study, we aimed to verify this hypothesis by exploring efficient planting systems (wheat–peanut (Arachis hypogaea L.) (W–P) rotation and wheat rotated with maize and peanut intercropping (W–M/P)) to achieve higher agricultural production in the Huang-Huai-Hai Plain. Using traditional W–M rotation as the control, we evaluated crop productivity, net returns, soil microorganisms (SMs), and soil organic carbon (SOC) fractions for three consecutive years. The results indicated that wheat yields were significantly increased under W–P and W–M/P (382.5–579.0 and 179.8–513.1 kg ha−1, respectively) compared with W–M. W–P and W–M/P provided significantly higher net returns (58.2 and 70.4%, respectively) than W–M. W–M/P and W–M retained the SOC stock more efficiently than W–P, increasing by 25.46–31.03 and 14.47–27.64%, respectively, in the 0–20 cm soil layer. Compared with W–M, W–M/P improved labile carbon fractions; the sensitivity index of potentially mineralizable carbon, microbial biomass carbon (MBC), and dissolved organic carbon was 31.5, 96.5–157.2, and 17.8% in 20–40, 10–40, and 10–20 cm soil layers, respectively. The bacterial community composition and bacteria function were altered as per the soil depth and planting pattern. W–M/P and W–M exhibited similar bacterial community composition and function in 0–20 and 20–40 cm soil layers. Compared with W–P, a higher abundance of functional genes, namely, contains mobile elements and stress-tolerant, and a lower abundance of genes, namely, potentially pathogenic, were observed in the 10–20 cm soil layer of W–M and the 0–20 cm soil layer of W–M/P. SOC and MBC were the main factors affecting soil bacterial communities, positively correlated with Sphingomonadales and Gemmatimonadales and negatively correlated with Blastocatellales. Organic input was the main factor affecting SOC and SMs, which exhibited feedback effects on crop productivity. In summary, W–M/P improved productivity, net returns, and SOC pool compared with traditional W–M rotation systems, and it is recommended that plant–soil–microbial interactions be considered while designing high-yield cropping systems.

Abstract We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child–Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002–1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003–1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006–1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009–1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029–1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child–Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761–0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

In order to stimulate learning interest among university students towards biochemistry and to improve learning outcomes, we performed a 10-week biochemistry Rain Classroom teaching experiment among students majoring in clinical medicine. Rain Classroom is a plug-in for WeChat, a smartphone instant messaging application. Teachers can post teaching resources on the Rain Classroom platform, administer tests, and communicate with students. Rain Classroom can also be used to automatically collect course learning data from students. When teaching is complete, questionnaire surveys can be conducted, and test scores can be outputted. Results showed that students were interested in the biochemistry Rain Classroom teaching application, and that the application increased their enthusiasm for the course materials. There were significant improvements in the learning outcomes in students given Rain Classroom teaching, compared to those given traditional PowerPoint slideshow lessons. We conclude that the Rain Classroom tool is a new mobile learning application that promotes self-learning and improves learning outcomes in biochemistry learning.

Fe–Mn–Al–C austenitic steels have promising prospects for lightweight applications, due to their low density, excellent strength, and ductility. But the specific strength ratio of these alloys are still low as compared to other alloys. Herein, an orthogonal rolling (OR) process was used to improve the mechanical strength of a Fe–28Mn–8Al–1C low-density steel. The effect of this deformation method on the microstructural evolution and mechanical properties was studied by means of microscopy techniques, e.g. optic, scanning and transmission electron microscope, electron backscattered diffraction, X-ray diffraction, micro hardness and tensile test measurements. Microstructural characterization results show that OR significantly promotes the activation of multiple slip systems within grains in the material. The development of more uniform deformation microstructure, compared with that that after unidirectional cold rolling to the same strain was mainly due the improvement of the uniformity of strain distribution by rolling deformation in multiple directions. It resulted in an average 84.5 nm sized ultrafine grain structures after 8-pass OR. The tensile and yield strengths were significantly increased to 1813 MPa and 1798 MPa, respectively. Despite of the still-exiting strength-ductility trade-off, a much higher elongation at tensile failure of 9.6% was achieved, compared to only 5.2% of unidirectional cold rolled material. This superior strength and ductility combination was likely promoted by the increased dislocation density and deformation substructures in forms of dislocation cells, and deformation twins induced by OR.

Cereal and legume intercropping has been widely adopted to increase crop productivity in sustainable farming systems worldwide. Among different intercropping combinations, millet and peanut intercropping can be adapted to most water-limited areas. However, there are few studies on the differences in yield characteristics and nitrogen use efficiency between millet/peanut intercropping and monocultures under different nitrogen (N) application rates. The objective of this study was to determine the yield advantages and economic benefits, as well as the appropriate N application rate, of millet/peanut intercropping. A two-year field experiment was conducted with three cropping patterns (monoculture millet, monoculture peanut and millet/peanut intercropping) and four N rates (0, 75, 150 and 225 kg ha−1). The results showed that the land equivalent ratio (LER) and net effect (NE) of the intercropping system reached their highest levels at the N input of 150 kg ha−1 in 2018 and 2019 (1.04 for LER, 0.347 Mg ha−1 for NE, averaged across two years). Millet was the dominant crop in the intercropping system (aggressivity of millet and peanut (Amp)>0, competitive ratio of millet and peanut (CRmp)>1), and millet yields achieved their highest values at N inputs of 225 kg ha−1 for monoculture and 150 kg ha−1 for intercropping. NUE reached its highest levels with N inputs of 150 kg ha−1 for all planting patterns over the two years. Intercropping combined with an N input of 150 kg ha−1 achieved the highest net income of 2 791 USD ha−1, with a benefit-cost ratio of 1.56, averaged over the two years. From the perspective of economics and agricultural sustainable development, millet/peanut intercropping at 150 kg N ha−1 seems to be a promising alternative to millet or peanut monoculture.

IntroductionIt is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC.MethodsWe obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts.ResultsHigh riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy.DiscussionCollectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.

Due to the scarcity of modeling samples and the low prediction accuracy of the matte grade prediction model in the copper melting process, a new prediction method is proposed. This method is based on enhanced generative adversarial networks (EGANs) and random forests (RFs). Firstly, the maximum relevance minimum redundancy (MRMR) algorithm is utilized to screen the key influencing factors of matte grade and remove redundant information. Secondly, the GAN data augmentation model containing different activation functions is constructed. And, the generated data fusion criterion based on the root mean squared error (RMSE) and the coefficient of determination (R2) is designed, which can tap into the global character distributions of the copper melting data to improve the quality of the generated data. Finally, a matte grade prediction model based on RF is constructed, and the industrial data collected from the copper smelting process are used to verify the effectiveness of the model. The experimental results show that the proposed method can obtain high-quality generated data, and the prediction accuracy is better than other models. The R2 is improved by at least 2.68%, and other indicators such as RMSE, mean absolute error (MAE), and mean absolute percentage error (MAPE) are significantly improved. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats.