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Abstract Anther development involves a series of important biological events that are precisely regulated by many genes. Although several important genes involved in rice anther development have been identified, the regulatory network involved in tapetal development and pollen wall formation is still largely unclear. PERSISTENT TAPETAL CELL 1 (PTC1) encodes a PHD-Finger protein, which plays a critical role in the regulation of tapetal cell death and pollen development in rice. Here, we report the isolation and characterization of a new allele ptc1-2 with 2-base deletion in the third exon, causing the absent of the PHD domain due to the sequence change. Cytological analysis revealed delayed tapetal PCD, defective pollen exine formation and abnormal ubisch bodies development. Transcriptome analysis revealed that genes related to pollen wall formation (secondary metabolism, phenylalanine synthesis, and cutin and wax biosynthesis pathways), cell death (cysteine and methionine metabolism and DNA repair pathways), and carbohydrate synthesis (starch and sucrose metabolism pathways) were significantly altered in ptc1-2 mutant. A total of 13 reported anther development genes exhibited significant expression changes in the ptc1-2 mutant. Yeast two-hybrid and BiFC analyses showed that PTC1 could interact with API5, an inhibitor of apoptosis, and the citrin-binding enzyme EDT1. This work is helpful in deepening the understanding of the regulatory network of male reproductive development in rice.

Abstract Objective To assess the impact of vertical integration (VI) within County-Level Integrated Health Organisations (CIHOs) on the costs of primary care inpatients. Methods This study assessed Xishui, a national pilot county for CIHOs, using inpatient claims data. The treatment group comprised 10,118 inpatients from 5 vertically integrated township health centres (THCs), while the control group consisted of 21,165 inpatients from 19 non-vertically integrated THCs. The periods from July 2020 to December 2021 and January 2022 to December 2022 were defined as pre- and post-policy intervention, respectively. The primary outcome variables were total health expenditures (THS), out-of-pocket (OOP) expenditures, and the proportion of OOP expenditures. Propensity score matching was employed to align inpatient demographics and disease characteristics between the groups, followed by a difference-in-differences analysis to evaluate the outcomes. Findings VI significantly increased THS (β = 0.1337, p 0.05). For the basic medical insurance for urban and rural residents, THS per case (β = 0.1343, p 0.05). The THS per case led by Xishui County People’s Hospital, the leading county medical sub-centre (CMSC), significantly increased (β = 0.1753, p 0.05). Increases in OOP expenditures per case were significant in CMSCs led by the People’s Hospital and the Traditional Chinese Medicine Hospital (β = 0.1782, p

BackgroundBreast cancer (BRCA) is the most prevalent type of cancer worldwide. As a highly heterogeneous cancer, it has a high recurrence rate. Since its biological behavior can be regulated by immunity and cuprotosis, so exploring potential therapeutic target to mediate immunity and cuprotosis is of great significance for BRCA therapy.MethodsThe immune-related genes and immune-cuprotosis-related deferentially expressed genes (ICR-DEGs) were identified by mining the TCGA database. Prognostic analysis, differential expression analysis, univariate and lasso regression analyses were used to determine their independent prognostic values. To evaluate the relationship between ICR-DEGs and immune scores, we constructed a prognostic risk model to evaluate immune checkpoints, and then the role of tumor immune microenvironment in BRCA was explored. Furthermore, anti-BRCA function and mechanism of islet amyloid poly-peptide (IAPP) mediated CD8+T cells were verified by means of flow cytometry, ELISA, and subcutaneous transplantation tumor model.ResultsAll results suggested that immune-cuprotosis-related genes were a potential predictor of BRCA’s response to immune checkpoint inhibitors and immunotherapy biomarkers. Thereby downregulation of IAPP reduced cuprotosis of CD8+T or Her2-CAR-T cells to promote the anti-BRCA function both in vitro and in vivo.ConclusionOur research had clarified the function and mechanism of IAPP in CD8+T cells, providing new ideas for improving the diagnosis and treatment of BRCA.

BackgroundControlling the growth of inpatient costs presents a major challenge in China’s healthcare system. China introduced a new case-based payment method, the “Diagnosis Intervention Packet” (DIP), to address the surge in hospitalization expenses. However, the influence of DIP payment reform on cost shifting among coronary heart disease (CHD) inpatients remains unclear.MethodsThis study focused on Zunyi, a national pilot city for DIP, utilizing inpatient claim data to assess the effects of DIP payment reform. We analyzed the influence on total health expenditures (THE), individual payments excluding reimbursement (IPER), proportion of IPER, copayments for category-B, proportion of copayments for category-B, copayments for category C, and proportion of copayments for category C per case for CHD inpatient.ResultsResults indicate a significant reduction in THE per case for CHD inpatients after the DIP reform (β = −0.1272, p

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97-/-), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97-/- mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97-/- mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-κB p65 was increased in GPR97-/- DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis.

Abstract Accurate on‐board state‐of‐health (SOH) prediction is crucial for lithium‐ion battery applications. This study presents an in situ prediction technique for minorly deformed battery SOH, utilizing a Gaussian process regression (GPR) model tuned by a Bayesian optimization algorithm. Unlike previous methods that interpret voltage–time data as incremental capacitance curves, our approach directly operates on raw voltage–time data. We apply gray relational analysis to select feature variables as inputs and train the Bayesian Gaussian process regression (BGPR) model using experimental data from batteries under different working conditions. To demonstrate the performance of the BGPR model, we compare it with stepwise linear regression, neural network, and Bayesian support vector machine (BSVM) models. The performance of these four models is evaluated using different performance indicators: mean absolute percentage error (MAPE), root‐mean‐squared percentage error (RMSPE), and coefficient of determination (R²). The results demonstrate that the BGPR model exhibits superior prediction performance with the lowest MAPE (0.11%), RMSPE (0.12%), and the highest R² (0.9915) for minorly deformed batteries. Furthermore, the BGPR model exhibits excellent robustness for SOH prediction of normal batteries under different conditions. This study provides an effective and robust method for accurate on‐board SOH prediction in lithium‐ion battery applications.

Abstract Background Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. Methods A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. Results DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. Conclusions DL-based model was established to accurately predict the survival rate of postoperative patients with GC.

Diabetes, a multifaceted metabolic disorder, poses a significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, and diabetic angiopathy. Recent studies have highlighted the intricate interplay between N6-methyladenosine (m6A) and non-coding RNAs (ncRNAs) in key pathways implicated in these diabetes complications, like cell apoptosis, oxidative stress, and inflammation. Thus, understanding the mechanistic insights into how m6A dysregulation impacts the expression and function of ncRNAs opens new avenues for therapeutic interventions targeting the m6A-ncRNAs axis in diabetes complications. This review explores the regulatory roles of m6A modifications and ncRNAs, and stresses the role of the m6A-ncRNA axis in diabetes complications, providing a therapeutic potential for these diseases.

Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, occupies a pivotal role in Asian traditional medicine and cuisine. The aerial parts and underground stems of H. cordata exhibit remarkable chemical diversity, particularly in essential oil. Nevertheless, the mechanisms regulating essential oil biosynthesis in H. cordata remain unclear. In this study, we present a quantitative overview of the proteomes across four tissues (flower, stem, leaf, and underground stem) of H. cordata, achieved through the application of the isobaric tag for relative and absolute quantitation (iTRAQ). Our research findings indicate that certain crucial ribosomal proteins and their interactions may significantly impact the production of essential oils in H. cordata. These results offer novel insights into the roles of ribosomal proteins and their associations in essential oil biosynthesis across various organisms of H. cordata.

Acute ischemic stroke (AIS) is the leading cause of disability worldwide, and recanalization therapy is significant in the hyperacute phase of AIS. However, reperfusion injury and hemorrhagic transformation after recanalization predict poor prognosis of AIS. How to minimize reperfusion injury and hemorrhagic transformation, which greatly improves the prognosis of vascular recanalization, is becoming a hot topic in AIS research and an urgent problem to be solved. A wealth of neuroprotective drug studies is now available, while some of the neuroprotectants have met with failure in human studies. It is discussed in this review about the progress in neuroprotective therapy for AIS based on understanding the pathophysiologic mechanisms of reperfusion injury and hemorrhagic transformation, as well as challenges in exploring new neuroprotectants.

Abstract Aim of the study To evaluate the clinical efficacy and safety of commonly used oral Chinese patent medicines for the treatment of coronary heart disease combined with hyperlipidemia in clinical practice through a network meta-analysis. Materials and methods PubMed, Embase, Cochrane Library, Web of Science, Wanfang, VIP, SinoMed, and CNKI databases were searched for all published randomized controlled trials (RCTs) on the treatment of coronary heart disease combined with hyperlipidemia using Chinese patent medicines. NoteExpress software was used to screen the literature obtained from the databases according to the inclusion and exclusion criteria. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. A network meta-analysis was performed using R 4.2.1. Subgroup analyses of outcome indicators were made based on conventional treatment (CT) methods. The incidence of adverse events in the included RCTs was statistically analyzed. A funnel plot was drawn using RevMan 5.4.1 software for the assessment of bias in the total clinical effectiveness rate. Finally, the quality of evidence for interventions with statistically significant differences was evaluated using the GRADE system. Results A total of 78 RCTs were included, involving 7,955 cases and 8 types of Chinese patent medicines, which were Tongxinluo Capsule, Naoxintong Capsule, Compound Danshen Dripping Pill, Shexiangbaoxin Pill, Songling Xuemaikang Capsule, Xuezhikang Capsule, Yindan Xinnaotong Capsule, and Zhibitai Capsule. A total of 24 RCTs reported the incidence of adverse events, but no statistically significant difference in the incidence of adverse events was found between the experimental and control groups in each study (P > 0.05). There was no obvious publication bias in all studies, but the overall quality of evidence in the included RCTs was low. Comparison of different intervention measures showed that Naoxintong Capsule + CT improved the cardiac index and cardiac output, and lowered the low-density lipoprotein cholesterol and total cholesterol levels. Tongxinluo Capsule + CT raised high-density lipoprotein cholesterol levels and reduced triglyceride levels. Xuezhikang Capsule + CT improved the total clinical effectiveness rate. Subgroup analyses showed that differences in CT did not cause heterogeneity in the results. Conclusion Compared with the use of CT alone, the combined use of Chinese patent medicines with CT can effectively improve the symptoms in patients with both coronary heart disease and hyperlipidemia.

BackgroundTo evaluate the methodological quality, report quality, and evidence quality of meta-analysis (MA) and systematic review (SR) on the efficacy of probiotics in the treatment of rheumatoid arthritis (RA).MethodsDatabases were used to identify eligible SRs/MAs until February 12, 2024. The methodological quality of the studies was assessed using AMSTAR-2 tool, the quality of the literature reports was scored using PRISMA checklists, and the quality of the evidence was graded using GRADE system.ResultsSeven reviews including 21 outcomes were included. Methodological quality of the included reviews was of general low, and the entries with poor scores were 2, 4, and 7. By PRISMA checklists, there were some reporting deficiencies, and quality problems were mainly reflected in the reporting registration and protocol, comprehensive search strategy and additional analysis. GRADE results elevated the quality of evidence to be low or very low overall.ConclusionsProbiotics may have a therapeutic effect on RA, based on the evidence provided by the SRs/MAs in this overview. Nevertheless, there is still a lack of conclusive evidence due to methodological limitations in the included research. To make trustworthy judgments regarding the efficacy of probiotics in the treatment of RA, more large-scale, high-quality randomized controlled trials are still required.

ObjectiveThe study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis.MethodsA total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated.ResultsThere was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8–86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%–25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine–Gray test p < 0.001).ConclusionThe competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.

BackgroundFruits are essential for health, yet their consumption in children is inadequate, with unclear influencing factors.MethodsA cross-sectional study was conducted among students in grades 3–12 in Beijing, China, from September 2020 to June 2021. Fruit consumption in children was surveyed using a self-administered food frequency questionnaire. Additionally, children’s food and nutrition literacy and family food environments were assessed using the “Food and Nutrition Literacy Questionnaire for Chinese School-age Children” and the “Family Food Environment Questionnaire for Chinese School-age Children,” respectively.ResultsOut of 10,000 participating children, 62.5% consumed fruit daily, with a lower frequency among boys (59.3%) compared to girls (65.8%), and among senior students (48.6%) compared to junior (63.6%) and primary students (71.2%). Fruit consumption was positively associated with other healthy foods (vegetables, whole grains, etc.) and negatively with unhealthy foods (sugared soft drinks). Children with higher food and nutrition literacy consumed fruits daily more frequently (82.4% vs. 59.9%, ORs = 2.438, 95%CI: 2.072–2.868). A significant positive correlation was found between children’s fruit consumption and a healthy family food environment (66.4% vs. 50.2%, OR = 1.507, 95%CI: 1.363–1.667).ConclusionThe results indicate that individual food and nutrition literacy and family food environment are key positive predictors of children’s fruit consumption. Future interventions should focus on educating children and encouraging parents to foster supportive family environments.

IntroductionBy implementing small-scale and efficient fertilization techniques, it is possible to enhance the activity of microorganisms, thereby improving soil carbon sequestration and ecological value in agriculture.MethodsIn this study, field experiments were conducted using various types of fertilizers: organic fertilizer, microbial fungal fertilizer, composite fertilizer, and an unfertilized control (CK). Additionally, different dosages of compound fertilizers were applied, including 0.5 times compound fertilizers, constant compound fertilizers, 1.5 times compound fertilizers and CK. Using advanced technologies such as Illumina MiSeq high-throughput sequencing, PICRUSt2 prediction, Anosim analysis, redundancy analysis, canonical correlation analysis, and correlation matrix, soil organic carbon (SOC) content and components, bacterial diversity, metabolic functions, and interaction mechanisms were examined in different fields.Results and DiscussionThe results showed pronounced effects of various fertilization modes on SOC and the bacterial community, particularly in the topsoil layer (0–20 cm). Organic fertilizer treatments increased the richness and diversity of bacterial communities in the soil. However, conventional doses and excessive application of compound fertilizers reduced the diversity of soil bacterial communities and SOC content. Additionally, different fertilization treatments led to an increase in easily oxidizable organic carbon (EOC) contents. Interestingly, the relationship between SOC components and soil bacteria exhibited inconsistency. EOC was positively correlated with the bacterial diversity index. Additionally, Chloroflexi exhibited a negative correlation with both SOC and its components. The influence of metabolismon primary metabolic functions on the content of SOC components in the soil was more notable. It included seven types of tertiary functional metabolic pathways significantly correlated with SOC components (p < 0.05).Purpose and SignificanceThese findings enhance the understanding of the relative abundance of bacterial communities, particularly those related to the carbon cycle, by adjusting agricultural fertilization patterns. This adjustment serves as a reference for enhancing carbon sinks and reducing emissions in agricultural soils.

Abstract Theoretically pulse wave velocity (PWV) is obtained by calculating the distance between two waveform probes divided by the time difference, and PWV ratio is used to assess the arterial stiffness gradient (SG) from proximal to distal. The aim was to investigate segmental upper-limb PWV (ulPWV) differences and the effects of hypertension and or aging on each ulPWV and SG. The study collected multi-waveform signals and conduction distances from 167 healthy individuals and 92 hypertensive patients. The results showed significant differences between ulPWVs (P

Abstract Background As global ageing continues to increase and many countries face challenges from the growing demand for long-term care. Drawing on the experiences of developed countries, developing countries have explored their own suitable long-term care insurance and have shown strong potential for development and research prospects. However, due to their late start, relevant research is underrepresented in the global research network and still needs to be supplemented. The present study hopes to examine the effect of long-term care insurance on healthcare utilization among the middle-aged and elderly from an empirical perspective, using China as an example. Methods Panel data from wave 3 (2015) and wave 4 (2018) of the nationally-representative China health and retirement longitudinal study were selected to obtain a sample of 661 processing participants and 16,065 control participants after matching the policy implementation time in the first pilot cities, and quantitative analysis was conducted using difference-in-differences propensity score matching estimator method to assess the net effect of long-term care insurance on health care utilization among the middle-aged and elderly adults. Results In the matched frequency-weighted regression difference-in-differences estimator results, long-term care insurance had a negative effect on the number and costs of annual hospitalizations at the 5% significance level (key variable values of − 0.0568101 and − 1236.309, respectively) and a non-significant effect on outpatient service utilization (P > 0.05). Further exploration of the heterogeneous effect of it revealed that implementation had a more significant negative effect on hospitalization utilization for middle-aged and older people in the East and for those with higher levels of education or attended care. Conclusion Long-term care insurance has played a role in controlling hospitalization costs but has not yet achieved the expected effect in controlling outpatient costs. The policy effects in terms of regional distribution and education level and care situation have been variable. The treatment plan of long-term care insurance needs to be improved, the supply of resources for long-term care services should be increased, and the promotion of long-term care insurance and health science should be given attention.

Abstract Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae. Graphical Abstract

Abstract The fruit of the dioecious plant Actinidia arguta has become a great attraction recently. It has long been difficult to distinguish the genders of hybrid seedlings before flowering, therefore increasing the expenditures of breeding. To produce reliable molecular marker for gender identification, this research utilized whole-genome re-sequencing of 15 males and 15 females from an 8-year-old cross population to develop gender specific markers. P51 and P11 were identified as sex-linked markers after verification. Both of these markers, according to the PCR results, only amplified a single band in male samples. These two markers were tested in 97 hybrids (52 females and 45 males) and 31 wild individuals (13 females and 18 males), with an accuracy of 96.88% and 96.09%, correspondingly. This research also verified the universalities of the two markers in Actinidia chinensis samples, and it could be inferred from the PCR results that neither marker was applicable to A. chinensis samples. The BLAST results of the two markers demonstrated that the two markers were closely aligned with different parts of the Y male-specific region of A. chinensis genome, thus they were likely to be useful for the research on the mechanism of sex determination of A. arguta. The two male-linked makers, P51 and P11, have already been used in sex-identification of A. arguta seedlings.

Background: Glucocorticoids (GCs) are widely used in the treatment of inflammatory liver diseases and sepsis, but GC’s various side effects on extrahepatic tissues limit their clinical benefits. Liver-targeting GC therapy may have multiple advantages over systemic GC therapy. The purpose of this study was to develop novel liver-targeting GC prodrugs as improved treatment for inflammatory liver diseases and sepsis. Methods: A hydrophilic linker or an ultra-hydrophilic zwitterionic linker carboxylic betaine (CB) was used to bridge cholic acid (CA) and dexamethasone (DEX) to generate transporter-dependent liver-targeting GC prodrugs CA-DEX and the highly hydrophilic CA-CB-DEX. The efficacy of liver-targeting DEX prodrugs and DEX were determined in primary human hepatocytes (PHH), macrophages, human whole blood, and/or mice with sepsis induced by cecal ligation and puncture. Results: CA-DEX was moderately water soluble, whereas CA-CB-DEX was highly water soluble. CA-CB-DEX and CA-DEX displayed highly transporter-dependent activities in reporter assays. Data mining found marked dysregulation of many GR-target genes important for lipid catabolism, cytoprotection, and inflammation in patients with severe alcoholic hepatitis. These key GR-target genes were similarly and rapidly (within 6 h) induced or down-regulated by CA-CB-DEX and DEX in PHH. CA-CB-DEX had much weaker inhibitory effects than DEX on endotoxin-induced cytokines in mouse macrophages and human whole blood. In contrast, CA-CB-DEX exerted more potent anti-inflammatory effects than DEX in livers of septic mice. Conclusions: CA-CB-DEX demonstrated good hepatocyte-selectivity in vitro and better anti-inflammatory effects in vivo. Further test of CA-CB-DEX as a novel liver-targeting GC prodrug for inflammatory liver diseases and sepsis is warranted.

Dropper failure seriously threatens the operation safety of a high-speed railway. In this work, for a simple chain suspension catenary, one span with five droppers is performed to establish a model and thus the effects of the moving load speed on dropper stress are investigated. First, the partial differential vibration equation of dropper is obtained through the mechanical analysis and converted into the finite difference equation. Then, we consider contact line as a beam element to obtain its motion equation. Furthermore, the boundary and initial conditions of five droppers are determined. Finally, the stresses of five droppers are numerically calculated and the effects of the moving load speed on dropper stress are investigated by writing a MATLAB code. The results suggest that the dropper location significantly affects its stress. Compared with other droppers, droppers II and IV have much more severe vibration amplitudes. Different moving load speeds could cause different stress change of each dropper. With the increasing speed, dropper experiences longer bending compression stage and the bending amplitude increases. The impact of the moving load speed on dropper stress is significant.

The efficacy of CAR-T cell therapy has been hindered by several factors that are intrinsic to the tumor microenvironment. Many strategies are being employed to overcome these barriers and improve immunotherapies efficacy. Interleukin (IL)− 4 is a cytokine released by tumor cells inside the tumor microenvironment and it can oppose T cell effector functions via engagement with the IL-4 receptor on the surface of T cells. To overcome IL-4-mediated immunosuppressive signals, we designed a novel inverted cytokine receptor (ICR). Our novel CAR construct (4/15NKG2D-CAR), consisted of an NKG2D-based chimeric antigen receptor, co-expressing IL-4R as an extracellular domain and IL-15R as a transmembrane and intracellular domain. In this way, IL-4R inhibitory signals were converted into IL-15R activation signals downstream. This strategy increased the efficacy of NKG2D-CAR-T cells in the pancreatic tumor microenvironment in vitro and in vivo. 4/15NKG2D-CAR-T cells exhibited increased activation, degranulation, cytokine release, and cytotoxic ability of NKG2D-CAR-T cells against IL-4+ pancreatic cell lines. Furthermore, 4/15NKG2D-CAR-T cells exhibited more expansion, less exhaustion, and an increased percentage of less differentiated T cell phenotypes in vitro when compared with NKG2D-CAR-T cells. That is why IL-4R/IL-15R-modified CAR-T cells eradicated more tumors in vivo and outperformed NKG2D-CAR-T cells. Thus, we report here a novel NKG2D-CAR-T cells that could overcome IL-4-mediated immunosuppression in solid tumors.

AbstractObjective To explore the predictive factors and establish a nomogram model for predicting relapse risk in primary membranous nephropathy (PMN).Methods The clinical, laboratory, pathological and follow-up data of patients with biopsy-proven membranous nephropathy were collected in the Affiliated Hospital of Qingdao University. A total of 400 PMN patients who achieved remission were assigned to the development group (n = 280) and validation group (n = 120) randomly. Cox regression analysis was performed in the development cohort to determine the predictive factors of relapse in PMN patients, a nomogram model was established based on the multivariate Cox regression analysis and validated in the validation group. C-index and calibration plots were used to evaluate the discrimination and calibration performance of the model respectively.Result Hyperuricemia (HR = 2.938, 95% CI 1.875–4.605, p

Abstract Background NK cell is one of innate immune cells and can protect the body from cancer-initiating cells. It has been reported that GPR116 receptor is involved in inflammation and tumors. However, the effect of GPR116 receptor on the NK cells remains largely unclear. Results We discovered that GPR116 −/− mice could efficiently eliminate pancreatic cancer through enhancing the proportion and function of NK cells in tumor. Moreover, the expression of GPR116 receptor was decreased upon the activation of the NK cells. Besides, GPR116 −/− NK cells showed higher cytotoxicity and antitumor activity in vitro and in vivo by producing more GzmB and IFNγ than wild-type (WT) NK cells. Mechanistically, GPR116 receptor regulated the function of NK cells via Gαq/HIF1α/NF-κB signaling pathway. Furthermore, downregulation of GPR116 receptor promoted the antitumor activity of NKG2D-CAR-NK92 cells against pancreatic cancer both in vitro and in vivo. Conclusions Our data indicated that GPR116 receptor had a negatively effect on NK cell function and downregulation of GPR116 receptor in NKG2D-CAR-NK92 cells could enhance the antitumor activity, which provides a new idea to enhance the antitumor efficiency of CAR NK cell therapy.

Lipoblastic nerve sheath tumors of soft tissue are characterized as schwannoma tumors that exhibit adipose tissue and lipoblast-like cells with signet-ring morphology. They have been documented to arise in various anatomic locations, including the thigh, groin, shoulder, and retroperitoneum. However, to our knowledge, this tumor has not been previously reported as a lymph node primary. We present herein the first case of a benign primary lipoblastic nerve sheath tumor arising in an inguinal lymph node in a 69-year-old man. Microscopic examination revealed a multinodular tumor comprising fascicles of spindle cells, as well as adipocytic and lipoblast-like signet-ring cell component in the context of schwannoma. Despite the presence of some bizarre cells with nuclear atypia, no obvious mitotic activity or necrosis was observed. Immunohistochemical analysis showed strong and diffuse expression of S-100, SOX10, CD56, and NSE in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. Sequencing analysis of the neoplasm identified six non-synonymous single nucleotide variant genes, specifically NF1, BRAF, ECE1, AMPD3, CRYAB, and NPHS1, as well as four nonsense mutation genes including MRE11A, CEP290, OTOA, and ALOXE3. The patient remained alive and well with no evidence of recurrence over a period of ten-year follow-up.

Purpose: This study aimed to conduct a bibliometric analysis of the data acquired and clarified the current research status of sexual health problems in patients with cancer, to provide a comprehensive visual perspective suitable as a reference for subsequent research. Methods: We searched the Web of Science Core Collection (WoSCC) up to April 30, 2023 to identify studies associated with sexual health problems in patients with cancer. CiteSpace was used to create visualization networks for countries, institutions, authors, and journals. Results: A total of 3183 publications related to sexual health problems in patients with cancer were collected from the WoSCC. In terms of volume, the USA (1259 papers) was the leading country, the Memorial Sloan Kettering Cancer Center (119 papers) was the leading institution, and Carter (39 papers) was the author with the most publications. The top-cited references and keywords were related to quality of life. The top five clusters of reference cocitation were ‘brachytherapy’, ‘prostate cancer’, ‘radical prostatectomy’, ‘hypogonadism’, and ‘breast cancer’. Meanwhile, the top five clusters of keyword cocitation were ‘breast cancer’, ‘prostate cancer’, ‘rectal cancer’, ‘testicular cancer’, and ‘sexual function’. The analysis of the top 25 references and keywords with the strongest citation bursts of published papers on sexual health problems in patients with cancer to reveal the research hotspots and trends. Conclusions: Research on sexual health among patients with cancer is constantly developing. The current research focuses on the impact of different treatment options for sexual health and quality of life of patients with breast, rectal, and genitourinary neoplasms. Exploring the long-term changing regularities of sexual function among cancer survivors and formulating sexual health interventions toward patient-reported outcomes and needs are key research directions.

BackgroundIntegrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research.MethodsData were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC.ResultsA total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus.ConclusionThe study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people’s understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies.

Introduction: Over the past decades, an increasing number of chromosomal translocations have been found in different STSs, which not only has value for clinical diagnosis but also suggests the pathogenesis of STS. Fusion genes can be detected by FISH, RT-PCR, and next-generation sequencing. One-step RT-PCR is a convenient method to detect fusion genes with higher sensitivity and lower cost.Method: In this study, 242 cases of soft tissue tumors were included, which were detected by one-step RT-PCR in multicenter with seven types of tumors: rhabdomyosarcoma (RMS), peripheral primitive neuroectodermal tumor (pPNET), synovial sarcoma (SS), myxoid liposarcomas (MLPS), alveolar soft part sarcoma (ASPS), dermatofibrosarcoma protuberans (DFSP), and soft tissue angiofibroma (AFST). 18 cases detected by one-step RT-PCR were further tested by FISH. One case with novel fusion gene detected by RNA-sequencing was further validated by one-step RT-PCR.Results: The total positive rate of fusion genes was 60% (133/213) in the 242 samples detected by one-step RT-PCR, in which 29 samples could not be evaluated because of poor RNA quality. The positive rate of PAX3–FOXO1 was 88.6% (31/35) in alveolar rhabdomyosarcoma, EWSR1–FLI1 was 63% (17/27) in pPNET, SYT–SSX was 95.4% in SS (62/65), ASPSCR1–TFE3 was 100% in ASPS (10/10), FUS–DDIT3 was 80% in MLPS (4/5), and COL1A1–PDGFB was 66.7% in DFSP (8/12). For clinicopathological parameters, fusion gene status was correlated with age and location in 213 cases. The PAX3–FOXO1 fusion gene status was correlated with lymph node metastasis and distant metastasis in RMS. Furthermore, RMS patients with positive PAX3–FOXO1 fusion gene had a significantly shorter overall survival time than those patients with the negative fusion gene. Among them, the FISH result of 18 cases was concordant with one-step RT-PCR. As detected as the most common fusion types of AHRR–NCOA2 in one case of AFST were detected as negative by one-step RT-PCR. RNA-sequencing was used to determine the fusion genes, and a novel fusion gene PTCH1–PLAG1 was found. Moreover, the fusion gene was confirmed by one-step RT-PCR.Conclusion: Our study indicates that one-step RT-PCR displays a reliable tool to detect fusion genes with the advantage of high accuracy and low cost. Moreover, it is a great tool to identify novel fusion genes. Overall, it provides useful information for molecular pathological diagnosis and improves the diagnosis rate of STSs.

The 5-year recurrence rate of thermal ablation for hepatocellular carcinoma (HCC) is high, and whether this treatment strategy induces systemic immune response remains elusive. This study aimed to investigate the effects of thermal ablation on HCC patients’ cytokine profiles and to explore the correlation of cytokine profiles with tumor recurrence after ablation. A total of 22 HCC patients were included in this prospective study. The levels of 27 cytokines in the peripheral blood of HCC patients were measured before ablation (baseline), week 1, and week 4 after ablation using a Bio-Plex Pro Human Cytokine 27-plex Assay kit. Cytokines showed different dynamic changing trends after ablation treatment. It was found that the level of IL-6 was significantly elevated at week 1 and returned to the baseline level at week 4 after ablation. The level of IL-10 was slightly reduced at week 1 and significantly decreased at week 4. The levels of MCP-1, macrophage inflammatory protein-1β (MIP-1β), and TNF-α were similarly reduced at week 1 and increased at week 4. The levels of IL-17, platelet-derived growth factor-BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) showed little to no change at week 1 while an observable increase at week 4. Patients with a high IL-10 level (2.99 pg/ml) at baseline and low levels of TNF-α (20.4 pg/ml), PDGF-BB (107.78 pg/ml), and RANTES (2303.94 pg/ml) at week 4 were at risk of tumor recurrence during 1-year follow-up. The results suggested that thermal ablation activated systemic immune responses by changing the levels of cytokines. The results also demonstrated that measurement of IL-10 at baseline, TNF-α, PDGF-BB, and RANTES at week 4 after ablation might predict the risk of tumor recurrence.

Objective: To investigate the tongue image features of patients with lung cancer and benign pulmonary nodules and to construct a lung cancer risk warning model using machine learning methods.Methods: From July 2020 to March 2022, we collected 862 participants including 263 patients with lung cancer, 292 patients with benign pulmonary nodules, and 307 healthy subjects. The TFDA-1 digital tongue diagnosis instrument was used to capture tongue images, using feature extraction technology to obtain the index of the tongue images. The statistical characteristics and correlations of the tongue index were analyzed, and six machine learning algorithms were used to build prediction models of lung cancer based on different data sets.Results: Patients with benign pulmonary nodules had different statistical characteristics and correlations of tongue image data than patients with lung cancer. Among the models based on tongue image data, the random forest prediction model performed the best, with a model accuracy of 0.679 ± 0.048 and an AUC of 0.752 ± 0.051. The accuracy for the logistic regression, decision tree, SVM, random forest, neural network, and naïve bayes models based on both the baseline and tongue image data were 0.760 ± 0.021, 0.764 ± 0.043, 0.774 ± 0.029, 0.770 ± 0.050, 0.762 ± 0.059, and 0.709 ± 0.052, respectively, while the corresponding AUCs were 0.808 ± 0.031, 0.764 ± 0.033, 0.755 ± 0.027, 0.804 ± 0.029, 0.777 ± 0.044, and 0.795 ± 0.039, respectively.Conclusion: The tongue diagnosis data under the guidance of traditional Chinese medicine diagnostic theory was useful. The performance of models built on tongue image and baseline data was superior to that of the models built using only the tongue image data or the baseline data. Adding objective tongue image data to baseline data can significantly improve the efficacy of lung cancer prediction models.

Post-harvest handling and ripening techniques have an impact on peach quality and shelf life, which has a big impact on consumer satisfaction and market competitiveness. This review paper examines recent advancements in ripening techniques and post-harvest technologies with the goal of improving peach fruit quality and sustainability. The factors impacting fruit quality after harvest and the physiological changes that occur throughout peach ripening are fully explained. For maintaining peach freshness and reducing losses, novel handling methods like modified atmosphere packaging (MAP) and controlled atmosphere storage (CAS) have been investigated. The study explores the possibilities of nanotechnology applications and low-temperature storage for prolonging shelf life while maintaining texture, flavor, and aroma. This study further analyzes the effectiveness and waste reduction potential of automation and mechanization in post-harvest activities. The paper also discusses ethylene-based and non-ethylene-based ripening agents, as well as innovative techniques including gene editing and RNAi technology for controlled and delayed ripening. Analyses are performed on how these technologies affect the sensory qualities and nutrient profiles of peaches. The study emphasizes the significance of sustainable practices in the peach industry by focusing on waste reduction, resource efficiency, and circular economy integration. Post-harvest technologies’ potential environmental consequences are taken into consideration, and the paper encourages more studies and cooperation to increase sustainability.

Abstract Background Long non-coding RNAs (lncRNAs) are widely involved in the pathogenesis of cancers. However, biological roles of lncRNAs in occurrence and progression of colorectal cancer (CRC) remain unclear. The current study aimed to evaluate the expression pattern of lncRNAs and messenger RNAs (mRNAs). Methods RNA sequencing (RNA-Seq) in CRC tissues and adjacent normal tissues from 6 CRC patients was performed and functional lncRNA-mRNA co-expression network was constructed afterwards. Gene enrichment analysis was demonstrated using DAVID 6.8 tool. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression pattern of differentially expressed lncRNAs. Pearson correlation analysis was applied to evaluate the relationships between selected lncRNAs and mRNAs. Results One thousand seven hundred and sixteenth differentially expressed mRNAs and 311 differentially expressed lncRNAs were screened out. Among these, 568 mRNAs were up-regulated while 1148 mRNAs down-regulated, similarly 125 lncRNAs were up-regulated and 186 lncRNAs down-regulated. In addition, 1448 lncRNA–mRNA co-expression pairs were screened out from 940,905 candidate lncRNA-mRNA pairs. Gene enrichment analysis revealed that these lncRNA-related mRNAs are associated with cell adhesion, collagen adhesion, cell differentiation, and mainly enriched in ECM-receptor interaction and PI3K-Akt signaling pathways. Finally, RT-qPCR results verified the expression pattern of lncRNAs, as well as the relationships between lncRNAs and mRNAs in 60 pairs of CRC tissues. Conclusions In conclusion, these results of the RNA-seq and bioinformatic analysis strongly suggested that the dysregulation of lncRNA is involved in the complicated process of CRC development, and providing important insight regarding the lncRNAs involved in CRC.

Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

Abstract Background We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). Methods The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. Results The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. Conclusions With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.

BackgroundAblative therapy is a recommended treatment for hepatocellular carcinoma (HCC) not only for its effective eradication of tumors, but also for its induction of host immunity. However, the high 5-year recurrence rate after ablation underlines the poor understanding of the antitumor immunity response. Here, we investigated the effects of thermal ablation on antitumor immunity.MethodsWe analyzed the dynamics of tumor-associated antigen (TAA)-specific immune responses and changes in peripheral blood mononuclear cell phenotype in patients with HCC before and after tumor ablation. We used the IFN-γ ELISPOT assay and immunophenotyping by flow cytometry to evaluate the effects of ablation on host immunity. The correlation between the T cell response and disease outcome was explored to uncover the efficacy of the immune response in inhibiting HCC recurrence.ResultsDifferent TAA-specific T cell responses were identified among patients before and after ablation. One week after ablation, there was an improved immune state, with a switch from the dominance of an AFP-specific T cell response to that of a SMNMS-specific T cell response, which was correlated with better survival. Furthermore, an improvement in immune status was accompanied by a lower level of PD1+ and Tim3+ T cells in CD8+ T cells. Although this functional state was not durable, there was a higher degree of AFP-specific T cell responses at 4-weeks post-ablation. Furthermore, T cells presented a more exhausted phenotype at 4-weeks post-ablation than at the 1-week timepoint.ConclusionsAblation elicits a transient antitumor immune response in patients with HCC by changing the profile of the T cell response and the expression of immune checkpoint molecules, which correlated with longer recurrence-free survival of patients with HCC.

BackgroundColon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC.MethodsThe Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated.ResultsCALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC.ConclusionOur NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

The distribution of elite soybean (Glycine max) cultivars is limited due to their highly sensitive to photoperiod, which affects the flowering time and plant architecture. The recent emergence of CRISPR/Cas9 technology has uncovered new opportunities for genetic manipulation of soybean. The major maturity gene E1 of soybean plays a critical role in soybean photoperiod response. Here, we performed CRISPR/Cas9-mediated targeted mutation of E1 gene in soybean cultivar Tianlong1 carrying the dominant E1 to investigate its precise function in photoperiod regulation, especially in plant architecture regulation. Four types of mutations in the E1 coding region were generated. No off-target effects were observed, and homozygous trans-clean mutants without T-DNA were obtained. The photoperiod sensitivity of e1 mutants decreased relative to the wild type plants; however, e1 mutants still responded to photoperiod. Further analysis revealed that the homologs of E1, E1-La, and E1-Lb, were up-regulated in the e1 mutants, indicating a genetic compensation response of E1 and its homologs. The e1 mutants exhibited significant changes in the architecture, including initiation of terminal flowering, formation of determinate stems, and decreased branch numbers. To identify E1-regulated genes related to plant architecture, transcriptome deep sequencing (RNA-seq) was used to compare the gene expression profiles in the stem tip of the wild-type soybean cultivar and the e1 mutants. The expression of shoot identity gene Dt1 was significantly decreased, while Dt2 was significantly upregulated. Also, a set of MADS-box genes was up-regulated in the stem tip of e1 mutants which might contribute to the determinate stem growth habit.

This study investigated the effect of protein levels (PLs) in dietary feed on the growth performance, muscle composition, and fiber recruitment in juvenile small yellow croaker (Larimichthys polyactis). A total of 900 fish weighing 10.67 ± 0.07 g were randomly allocated into six groups that were fed dietary PLs of 40%, 42.5%, 45%, 47.5%, 50%, and 52.5%, respectively. Each group was sorted into 1.0 × 1.0 × 1.0 m3 cages, with 50 individuals per cage. The fish were fed for 50 days; thereafter, all of live fish were analyzed for weight and length, 15 individuals per group were randomly selected for sampling and analysis. The weight gain rate and specific growth rate significantly increased when the dietary PL increased from 40% to 47.5% (P

Abstract Pancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors. 4.1R has been reported to suppress the anti-tumor activity of T cell responses. In this study, we investigated the anti-tumor activity of 4.1R deletion in natural killer group 2D (NKG2D)-CAR T cells against PC. The CAR T cells were obtained by transfecting T cells with lentiviral vector carrying NKG2D-CAR, NC-NKG2D-CAR, or KD2-NKG2D-CAR. In vitro, NKG2D-CAR T cells showed higher cytotoxicity than Mock T cells. However, compared to NKG2D-CAR T cells, furtherly higher cytotoxicity against PC cells in a dose-dependent manner was found in KD2-NKG2D-CAR T cells. In addition, the proliferation rate and cytotoxic activity of KD2-NKG2D-CAR T cells were significantly higher than those of NKG2D-CAR T cells. Besides, the inhibitory receptors PD-1 and TIM-3 were expressed in lower level on KD2-NKG2D-CAR T cells. In vivo, KD2-NKG2D-CAR T cells suppressed tumor growth more effectively in a xenograft model compared to NKG2D-CAR T cells. Mechanistically, 4.1R regulated CAR T cell function via activating ERK signaling pathway. Therefore, the study provides a new idea to enhance the anti-tumor efficiency of CAR T therapy.

Plant-derived polysaccharides have demonstrated promising anti-cancer effects via immune-regulatory activity. The aim of the current study was to compare the chemical property and the anticancer effects of polysaccharides extracted from the sporoderm-removed spores of the medicinal mushroom Ganoderma lucidum (RSGLP), which removed the sporoderm completely, with polysaccharides extracted from the sporoderm-broken spores of G. lucidum (BSGLP). We found that RSGLP has a higher extraction yield than BSGLP. HPGPC and GC-MS results revealed that both RSGLP and BSGLP are heteropolysaccharides, but RSGLP had a higher molecular weight and a different ratio of monosaccharide composition than BSGLP. MTT and flow cytometry results demonstrated that RSGLP exhibited much higher dose-efficacy in inhibiting cell viability and inducing apoptosis than BSGLP in 8 cancer cell lines representing colon (HCT116 and HT29), liver (HepG2 and Huh-7), breast (MDA-MB-231 and MCF-7), and lung cancers (NCI-H460 and A549). Furthermore, RSGLP is more effective in inhibiting HCT116 and NCI-H460 xenograft tumor growth and inhibiting tumor-induced splenomegaly than BSGLP in nude mice, suggesting a better effect on regulating immunity of RSGLP. Next, we found that RSGLP is more potent in inhibiting the level of serum inflammatory cytokines in nude mice, and in inhibiting the activation of macrophage RAW264.7 and the expression of the inflammatory mediators IL-1β, TNF-α, iNOS, and COX-2 in vitro. This is the first study to compare the chemical properties, anti-cancer, and immune-regulatory effects of RSGLP and BSGLP using multiple cancer cell lines. Our results revealed that the sporoderm-removed spores of G. lucidum (RSGL) and RSGLP may serve as new anticancer agents for their promising immune-regulatory activity.

BackgroundChina advocates a health insurance system with social health insurance (SHI) as the main body and private health insurance (PHI) as the supplement. The study of PHI's complementary role in health is conducive to providing evidence for PHI's policy expansion and encouraging the public to participate in PHI, which is insufficient in China.MethodsWe used the three-wave balanced panel data of the China Health and Retirement Longitudinal Survey (CHARLS). Taking the ownership of supplementary PHI as the independent variable and EQ-5D index scores as the dependent variable, the panel instrumental variable (IV) method was used to analyze the impact of participation in PHI on health. We also assessed the heterogeneity of the health effects of PHI between chronic and non-chronic disease groups and between low- and high-income groups.ResultsThe coverage rate of PHI at baseline was 10.53%. The regression results showed that participating in PHI on the basis of SHI could result in an additional 8.21% health gain (p < 0.001). At the same time, PHI had greater health gain for chronic disease population than for healthy population (9.25 vs. 6.24%, p < 0.001), and greater health gain for high-income population than for low-income population (8.32 vs. 5.31%, p < 0.001).ConclusionParticipating in supplementary PHI can effectively enhance the health status of the insured, and has a more significant effect on patients with chronic diseases. The development of PHI should be further supported, while the health inequality in different income groups should be paid attention to.

Liquid chromatographic separation technique coupled with fluorescence detector (LC-FLD) has been one of the primary sensitive and selective analytical techniques in various science areas including environmental, food, biological, biomedicine etc. Its significance relies on several analytical advantages including cost-effectiveness, enhanced sensitivity, and selectivity performance. However, the desired applications of this technique and detection limits are not always possible without target analytes derivatization. When analytes manipulation is carried out by mere light, the mechanism is called photoderivatization or photochemical reaction. This addition of photochemical reactor has significantly enhanced the LC-FLD capability for selective, sensitive, and reproducible determination of variety of analytes such as pesticides, pharmaceutical drugs, flavonoids, vitamins etc. as compared to chemical pre/post-column derivatization. Herein, we have comprehensively and systematically summarized the development, instrumentation and applications of liquid chromatography-photoinduced fluorescence technique (LC-hv-FLD) to analyze a large number of analytes-residues in various matrices published between the years i.e., 2000 to 2022 along with some outstanding and important contributions before this time span. Moreover, the essential characteristic, advantages/disadvantages, challenges, and future prospects have also been highlighted. We expect this manuscript to be a useful key reference for the future development in fluorescence based chromatographic analysis and inspire new ideas and discoveries in the direction of reagent-less and online derivatization of intrinsically non-fluorescent analytes.

The leaf is the main site of photosynthesis and is an important component in shaping the ideal rice plant architecture. Research on leaf morphology and development will lay the foundation for high-yield rice breeding. In this study, we isolated and identified a novel curling leaf mutant, designated curling leaf 1 (cl1). The cl1 mutant exhibited an inward curling phenotype because of the defective development of sclerenchymatous cells on the abaxial side. Meanwhile, the cl1 mutant showed significant reductions in grain yield and thousand-grain weight due to abnormal leaf development. Through map-based cloning, we identified the CL1 gene, which encodes a MYB transcription factor that is highly expressed in leaves. Subcellular localization studies confirmed its typical nuclear localization. Transcriptome analysis revealed a significant differential expression of the genes involved in photosynthesis, leaf morphology, yield formation, and hormone metabolism in the cl1 mutant. Yeast two-hybrid assays demonstrated that CL1 interacts with alpha-tubulin protein SRS5 and AP2/ERF protein MFS. These findings provide theoretical foundations for further elucidating the mechanisms of CL1 in regulating leaf morphology and offer genetic resources for practical applications in high-yield rice breeding.

With the increase in the modulation rate of thin-film lithium niobate (LiNbO3, LN) modulators, the multi-physical field coupling effect between microwaves, light, and heat becomes more significant. In this study, we developed a thin-film LN modulator model using undoped pure LN thin film and T-shaped slow-wave electrodes. Furthermore, we utilized this model to simulate the microwave heating and light heating situations of the modulator. The temperature of the LN modulator was analyzed over time and with different signal frequencies. We also studied the influence of temperature rise on microwave and light signals, and we analyzed the change of S parameters and the Phase Shift of the light signal caused by temperature rise. Finally, we improved the thermodynamic characteristics of the modulator by adding a diamond heat dissipation layer. The diamond was obtained through the Chemical Vapor Deposition (CVD) technique and was a polycrystalline diamond. After adding the diamond heat dissipation layer, the temperature rise of the modulator was significantly improved, and the adverse effects of temperature rise on microwave signals were also significantly reduced.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignant cancer type worldwide. Radiosensitivity has been shown to be significantly increased in patients with human papillomavirus (HPV)-positive HNSCC compared with HPV-negative patients. However, the clinical significance of HPV and its regulatory mechanisms in HNSCC are largely unknown. The aim of our study was to explore the regulatory mechanism of miR-27a-3p in the radiosensitivity of HPV-positive HNSCC cells. Methods E6-overexpressing and E6-knockdown HNSCC cell lines were generated and the transfection efficiencies were evaluated by quantitative real-time PCR (RT-qPCR) and western blotting. The expression of miR-27a-3p and DiGeorge syndrome critical region 8 (DGCR8) was examined by RT-qPCR after transfection with E6 overexpressing plasmid or E6 siRNA. The effects of miR-27a-3p on the radiosensitivity of HNSCC cells were explored by a colony formation and TUNEL staining assays. Bioinformatic tools and luciferase reporter assays were used to identify that SMG1 is the direct target of miR-27a-3p. Furthermore, the effect of E6 overexpression on the regulation of the miR-27a-3p/SMG1 axis was investigated. Results In our study, we found overexpression of HPV E6 upregulated the expression of DGCR8 and miR-27a-3p in HNSCC cells. We next confirmed that DGCR8 positively regulated the expression of miR-27a-3p in HNSCC cells. The luciferase reporter gene results verified that miR-27a-3p targeted the 3’UTR of SMG1 mRNA. MiR-27a-3p mimics transfection resulted in a decrease in SMG1 expression and miR-27a-3p inhibitor transfection increased SMG1 expression. Apoptotic activity of HNSCC cells was significantly increased in miR-27a-3p mimics HNSCC cells compared with control HNSCC cells. After treatment with 4 Gy irradiation, UM-SCC47 cells transfected with miR-27a-3p inhibitor or SMG1 overexpressing plasmid formed more colonies than the corresponding control cells. Furthermore, the rescue experiments demonstrated that HPV16 E6 improved the radiosensitivity of HNSCC cells by targeting miR-27a-3p/SMG1. Conclusion Our study demonstrated that HPV16 E6 activated the DGCR8/miR-27a-3p/SMG1 axis to enhance the radiosensitivity. Our findings might provide a novel therapeutic target to improve the response of HNSCC to radiotherapy.

In this paper, the influence of wind load on the stress characteristics of dropper for a high-speed railway is studied. The section method is used to obtain the vibration equation of the dropper, and the finite difference method is used to convert the partial differential equation of the dropper vibration into a finite difference equation. Through the force analysis of the contact line section upwind, the vibration equation of the contact line with air damping is obtained. Thus, the partial differential equation of the motion can determine the initial and boundary conditions of each dropper. The MATLAB program is written to obtain the stress change diagram of each dropper, and the influence of wind load on the stress characteristics of the dropper is analyzed. The results show that the maximum tensile and compressive stresses of each dropper are different due to the difference of wind load and dropper location, and the dropper in the middle location is most sensitive to the change of wind load. At a low wind speed, there are immediate rebound and obvious attenuation vibration stages during the stress change of dropper. In addition, with the increasing speed of wind load, the stress amplitude and the maximum tensile stress of dropper do not almost change or decrease except the middle dropper.

Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.

We examined the effects of Cd and Zn exposure on the photosynthetic function and the tolerant mechanisms of ROS metabolism in tobacco leaves. The results showed that the photosynthesis inhibition caused by Cd exposure was due to the limitation of both stomatal and non-stomatal factors, while Zn exposure only showed a significant effect on the Gs of tobacco leaves. Cd increased the generation rate of O2•– and the content of H2O2, but Zn did not lead to the ROS burst. Cd enhanced the POD activity, but inhibited SOD and CAT activities. The activities of SOD and POD significantly increased under Zn exposure. Cd inhibited the activity and expression of APX. The up regulation of GPX, GR and GST expression and the increase of their activities also play a positive role in the adaptation to Cd. Although Zn inhibited the activities of APX and GPX, it had little effect on other enzyme activities and protein expression in AsA-GSH cycle. TPX and TrxR activities, Trx-Prx pathway-related proteins are very sensitive to Cd. However, only PrxQ and 2-Cys Prx BAS1, which are located in chloroplast, and Trx-HFC164 were significantly down-regulated in Trx-Prx pathway under Zn exposure.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p