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Abstract The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022. The primary outcomes were HCC, hepatic decompensation, and mortality. Multivariable proportional hazards model was used to assess the impact of SVR and cirrhosis status. The cohort consisted of 1272 patients with SVR (92.1%) and 109 without SVR (7.9%), with a median follow-up of 61 months. The incidence of HCC was significantly lower in the SVR group (5.1 per 1000 person-years) compared to the no-SVR group (15.0 per 1000 person-years). Achieving SVR was associated with a significantly reduced risk of HCC (adjusted hazard ratio: 0.32; 95% CI 0.16–0.67). Cirrhosis was linked to an increased risk of developing HCC and hepatic decompensation. These findings highlight the importance of early DAA treatment, particularly for patients with cirrhosis.

Objectives: This study aimed to investigate the timing sequence recovery effects of single and repeated Mild Hyperbaric Oxygen Therapy (MHOT) on muscle fatigue induced by cycling exercise through a comprehensive set of parameters. Methods: This study employed a controlled crossover design involving 12 Chinese secondary national-level male athletes. Each participant completed two identical trials over six days. Each trial consisted of a 90-min cycling exercise followed by either a Control (CON) intervention (1 atm absolute (ATA), 20.9 % oxygen, 60 min) or MHOT intervention (1.25 ATA, 26%–28 % oxygen, 60 min). Various physiological parameters including Rating of Perceived Exertion (RPE), Heart Rate (HR), Peripheral Oxygen Saturation (SpO2), Perfusion Index (PI%), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Lactic Acid (LA), Blood Urea Nitrogen (BUN), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Standing Long Jump Distance (SLJ) were measured at six different time points throughout the trials. Results: RPE revealed that the MHOT group experienced reduced subjective fatigue in comparison to the CON group (P

Abstract ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.

Abstract Objectives Supplemental parenteral nutrition (SPN) is recommended to add when enteral nutrition alone is not sufficient. This research aims to evaluate the effect of preoperative SPN in patients with gastric cancer. Methods A total of 180 patients with gastric cancer were divided into three groups (60 patients per group) according to different nutritional support scheme. The primary endpoint was the changes in nutrition and inflammatory, while the secondary endpoint included the changes in prognosis. Results Compared with the control group, there were significant differences in nutrition and inflammation related indicators in the oral nutrition supplement (ONS) group and the SPN + ONS group (P

Abstract Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability.

Abstract With the increasing age of the population worldwide, the incidence rate of Parkinson’s disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease. In the present study, whole transcriptome sequencing was used to obtain the mRNA and miRNA expression profiles in a PD mouse model, which revealed the pathogenesis of PD. The transcription factor RUNX3 upregulated the miR-186-3p expression in the PD model. Furthermore, the high miR-186-3p expression in PD can be targeted to inhibit the DAT expression, resulting in a decrease in the dopamine content of dopaminergic neurons. Moreover, miR-186-3p can be targeted to inhibit the IGF1R expression and prevent the activation of the IGF1R–P-PI3K–P-AKT pathway, thus increasing the apoptosis of dopaminergic neurons by regulating the cytochrome c–Bax–cleaved caspase-3 pathway. Our research showed that the RUNX3–miR-186-3p–DAT–IGF1R axis plays a key role in the pathogenesis of PD, and miR-186-3p is a potential target for the treatment of PD.

Abstract Introduction To determine any significant associations between abdominal aortic calcification (AAC) and clinical manifestations of pain symptoms following endoscopic lumbar discectomy. Methods Patients sequentially presenting with a history of unilateral radiculopathy with or without back pain, and with magnetic resonance imaging (MRI)-confirmed diagnosis of posterolateral disc herniation between August 2021 and December 2023 were eligible for inclusion in the study. All patients underwent endoscopic discectomy at our center during the study period. AAC stages were classified based on the Kauppila classification system using lateral lumbar radiographs. Results Between August 2021 and December 2023 a total of 120 patients were included in the study for analysis, of whom 82 (68.3%) exhibited mild AAC and 38 (31.7%) had moderate-severe AAC. Analyses using the multivariate linear regression model revealed a significant correlation between AAC comorbidity and postoperative clinical outcomes. At 1 year post-surgery, the mean change in leg pain following endoscopic lumbar discectomy was significantly less for patients with moderate-severe AAC (5.0 points) than for patients with mild ACC (p

Background: The standard of care for stage 1 NSCLC is upfront surgery followed by surveillance. However, 20–30% of stage 1 NSCLC recur. There is an unmet need to identify individuals likely to recur who would benefit from frequent monitoring and aggressive cancer treatments. Collagen 1 (Col1) fibers detected by second harmonic generation (SHG) microscopy are a major structural component of the extracellular matrix (ECM) of tumors that play a role in cancer progression. Method: We characterized Col1 fibers with SHG microscopy imaging of surgically resected stage 1 NSCLC. Gene expression from RNA sequencing data was used to validate the SHG microscopy findings. Results: We identified a significant (p ≤ 0.05) increase in the Col1 fiber volume in stage 1 NSCLC that recurred. The increase in Col1 fiber volume was supported by significant increases in the gene expression of Col1 in invasive, compared to noninvasive, lung adenocarcinoma. Significant differences were identified in the gene expression of other ECM proteins, as well as CAFs, immune checkpoint markers, immune cytokines, and T-cell markers. Conclusion: Col1 fiber analysis can provide a companion diagnostic test to evaluate the likelihood of tumor recurrence following stage 1 NSCLC. The studies expand our understanding of the role of the ECM in NSCLC recurrence.

Abstract Background To identify the sensitivity, specificity, and overall diagnostic accuracy of infrared thermography in diagnosing lumbosacral radicular pain. Methods Patients sequentially presenting with lower extremity pain were enrolled. A clinical certainty score ranging from 0 to 10 was used to assess the likelihood of lumbosacral radicular pain, with higher scores indicating higher likelihood. Infrared Thermography scans were performed and the temperature difference (ΔT) was calculated as ΔT = T1 - T2, where T2 represents the skin temperature of the most painful area on the affected limb and T1 represents the skin temperature of the same area on the unaffected limb. Upon discharge from the hospital, two independent doctors diagnosed lumbosacral radicular pain based on intraoperative findings, surgical effectiveness, and medical records. Results A total of 162 patients were included in the study, with the adjudicated golden standard diagnosis revealing that 101 (62%) patients had lumbosacral radicular pain, while the lower extremity pain in 61 patients was attributed to other diseases. The optimal diagnostic value for ΔT was identified to fall between 0.8℃ and 2.2℃, with a corresponding diagnostic accuracy, sensitivity, and specificity of 80%, 89%, and 66% respectively. The diagnostic accuracy, sensitivity, and specificity for the clinical certainty score were reported as 69%, 62%, and 79% respectively. Combining the clinical certainty score with ΔT yielded a diagnostic accuracy, sensitivity, and specificity of 84%, 77%, and 88% respectively. Conclusion Infrared thermography proves to be a highly sensitive tool for diagnosing lumbosacral radicular pain. It offers additional diagnostic value in cases where general clinical evaluation may not provide conclusive results. Trial registration ChiCTR2300078786, 19/22/2023.

Abstract Objectives To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. Methods The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan–Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. Results One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. Conclusion A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. Critical relevance statement MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. Key Points MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA. Graphical Abstract

The accumulation of coal gangue results in serious environmental pollution, it is urgent and necessary to comprehensive, high value and efficient utilization of coal gangue. The resource utilization of coal gangue by calcination is important. In terms of the problems of high energy consumption and low efficiency, the use of sodium salt types and calcination process for coal gangue whitening has been investigated. Raw and calcined coal gangue were thoroughly characterized with respect to phases constituent, microstructures, pore structures and chemical bonds.Based on above investigations, the whitening mechanism and volatile products obtained from sodium chloride calcined coal gangue process were further analyzed by simultaneous thermogravimetry-Fourier transform infrared spectroscopy-Mass spectrometer (TG-FTIR-MS). Results show that after being calcined with sodium chloride at 860 ℃, the whiteness of raw coal gangue was upgraded from 38.5% to 86.0%. All the carbon and pyrite (FeS2) contained in coal gangue was oxidized and correspondingly converted into hematite (Fe2O3) by desulfurization and the total amount of hematite and rutile (TiO2) was reduced to 0.27%. The pore structural characteristics changed little at calcination temperature between 800 and 860 ℃. However, the calcination at 950 ℃ resulted in generation of spherical mullite, and a significant decrease in specific surface area and pore volume from 12.91 m2/g and 0.056 cm3/g for raw coal gangue to 6.58 m2/g and 0.031 cm3/g, respectively. The whiteness increased slightly at calcination time between 30 and 90 min (85.3% to 86.6%). Meanwhile, the whiteness changed little at calcination time between 90 and 150 min (86.6% to 86.7%). The addition of NaCl had little impact on the chemical bonds of calcined coal gangue. The evolution of mineral components in the calcination stage was relatively low, and the main volatile products were H2O, HCl, CO2 and H2S. Moreover, NaCl reacted with SiO2 and H2O to decompose into HCl gas, which removes iron and titanium by the volatilization of the respective chlorides. The chlorinated products escaped from the surface of the material layer and discharged, resulting in a purified and whitened coal gangue.

In order to study the stability and influencing factors of the end face roof of the full-mechanized mining face, a mechanical model of tip-to-face roof stability was developed in this study with a combination of the energy method and the “roof-support-coal” system. Meanwhile, the load monitoring system on the canopy of the support and the digital image measuring technique were utilized in a physical simulation model to analyze the influence factors of tip-to-face roof fall, the roof failure characteristics and the evolution characteristics of pressure distribution on the canopy of the support. The results showed that the stability coefficient of the immediate roof within 1 m behind the coal wall was less than 0 based on the mechanical model of tip-to-face roof stability, indicating a high risk of roof collapse in this area. In addition, the vertical and horizontal displacement of the immediate roof increased with the increase of the distance behind the coal wall. Enhancing the working resistance of the support can also reduce the roof subsidence, and the higher roof cohesion and internal friction angle can improve the tip-to-face roof stability. On the other hand, the tip-to-face roof caving, roof broken and roof crushing were observed in sequence during the process of the physical simulation experiments. The middle section of the canopy showed the largest measured pressure, followed by the front and rear sections of the canopy in the descending order. When the roof was intact, the support showed adequate setting load and working resistance, and the interaction between the support and the strata was in good condition. As the roof was broken and led to an unfavorable support position, the support showed a loss of working resistance or an unbalanced loading condition, which may easily result in the crack development in the roof, tip-to-face roof cavity, an iron-bound support and an awful support-strata coupling. According to the digital image measuring technique, the maximum shear strain was found near the tip-to-face area during the tip-to-face roof caving stage. Lastly, it can be concluded that the coupling between the support and strata is closely correlated to the tip-to-face roof stability. Thus, maintaining a good support-strata interaction is beneficial to the stability of the tip-to-face roof.

In some radioisotope production experiments，100 MeV high-current proton cyclotron is required to extract a single-turn beam to meet the experimental requirements，but at present，there is a serious problem of turn overlap when the beam is extracted，and a beam screening device needs to be designed to improve the quality of the drawn beam. The beam screening device has a frame structure and slit motion system based on the cyclotron，and a control system based on PLC design to control the stepper motor and use the electronic ruler and PID control algorithm to achieve closed-loop control. After many times of operation and debugging，the motion accuracy of the mechanical device is ±0.2 mm，and the beam screening can be realized during the operation of the accelerator，which has reference significance for the design and manufacture of the cyclotron beam screening device.

Abstract Background Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). Methods We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual’s diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. Results Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. Conclusions In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

Abstract The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

IntroductionEmergency medical service (EMS) serves as a pivotal role in linking injured road users to hospitals via offering first aid measures and transportation. This paper aims to investigate the effect of emergency medical service (EMS) response time on the fatality risk of freeway crashes.MethodsCrash injury severity data from Kaiyang Freeway, China in 2014 and 2015 are employed for the empirical investigation. A Bayesian random parameters spatial logistic model is developed for analyzing crash severity.ResultsBayesian inference of the random parameters spatial logistic model demonstrates the importance of reducing EMS response time on minimizing the fatality risk of freeway crashes. Fatality odds would increase by 2.6% for 1 min increase in EMS response time. Additionally, vehicle type, crash type, time of day, horizontal curvature, vertical grade, and precipitation are also found to have significant effects on the fatality probability of freeway crashes.ConclusionIt is crucial to reduce EMS response time to decrease the fatality likelihood of freeway crashes. Some countermeasures have been proposed to shorten EMS response time.

Abstract Introduction An increasing body of evidence suggests a close association between COVID‐19 infection and the safety of PD‐1/PD‐L1 inhibitor therapy in cancer patients. However, the available data concerning these impacts remain limited and occasionally contradictory. Material and Methods We conducted a retrospective analysis of cancer patients who received PD‐1/PD‐L1 inhibitor therapy at the same institution from November 2022 to May 2023. After excluding patients with missing information, a total of 224 cases were included. In our study, immune‐related adverse events (irAEs) that occurred during the hospitalization of patients were included in the analysis. Further analysis of inter‐subgroup differences was conducted following a 1:2 propensity score matching. Statistical analyses were performed using the Fisher's exact, chi‐squared, and Mann–Whitney U‐tests. Result The results showed that no statistically significant differences between the two subgroups in the incidence of irAEs, changes in immune function before and after using PD‐1/PD‐L1 inhibitors, and alterations in hepatic and renal function (p > 0.05). Conclusion Our findings suggest that infection with COVID‐19 does not significantly impact the safety of PD‐1/PD‐L1 inhibitors in cancer patients. Most cancer patients used PD‐1/PD‐L1 inhibitors during COVID‐19 infection (asymptomatic or mild infection) did not experience exacerbation of their underlying condition, nor did they exhibit a substantial increase in toxic side effects.

In this study, Lagenaria siceraria (Molina) Standl polysaccharides (LSP) was prepared using the water-alcohol precipitation method to evaluate its effects on growth performance, slaughter performance, cytokines, immune organ indices, cecal short-chain fatty acids (SCFAs), and microbial community structure in broiler chickens when added to the basal diet. Seventy-five broiler chickens were selected and randomly divided into five groups, with 15 chickens per group. All groups were fed a basal diet for 7 days. From 7 days of age, the control group continued to receive the basal diet, while the positive drug group was fed a diet supplemented with Astragalus polysaccharides (APS, 100 g/kg) in addition to the basal diet. The experimental groups were fed diets containing different concentrations of LSP (50, 100, and 200 g/kg) in addition to the basal diet, and the supplementation continued for 42 days. The findings indicated that the incorporation of LSP into the feed significantly enhanced average daily weight gain (ADWG), average daily feed intake (ADFI), feed to gain ratio (F/G), dressing percentage, percentage of breast muscle, percentage of leg muscle, and percentage of abdominal fat while concurrently reducing drip loss rate and cooking loss rate (p

Objective We examined the factors influencing hospitalization and prognosis among patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. Methods In total, 267 patients diagnosed with NSCLC who were receiving treatment with third-generation EGFR-TKIs were included in our retrospective study. Data on patients’ demographics, clinical characteristics, and survival were collected and analyzed. Results Over a mean follow-up of 18 months, 80.5% (215/267) of the patients contracted COVID-19, and 12.6% (27/215) of these patients were hospitalized for COVID-19 treatment. Vaccinated patients, those with body mass index (BMI) ≥22.3 kg/m 2 , and those with no comorbidities had lower rates of infection and hospitalization than unvaccinated patients, those with BMI

PurposeVolumetric modulated arc therapy (VMAT) is a new treatment modality in modern radiotherapy. To ensure the quality of the radiotherapy plan, a physics plan review is routinely conducted by senior clinicians; however, this process is less efficient and less accurate. In this study, a multi-task AutoEncoder (AE) is proposed to automate anomaly detection of VMAT plans for lung cancer patients.MethodsThe feature maps are first extracted from a VMAT plan. Then, a multi-task AE is trained based on the input of a feature map, and its output is the two targets (beam aperture and prescribed dose). Based on the distribution of reconstruction errors on the training set, a detection threshold value is obtained. For a testing sample, its reconstruction error is calculated using the AE model and compared with the threshold value to determine its classes (anomaly or regular). The proposed multi-task AE model is compared to the other existing AE models, including Vanilla AE, Contractive AE, and Variational AE. The area under the receiver operating characteristic curve (AUC) and the other statistics are used to evaluate the performance of these models.ResultsAmong the four tested AE models, the proposed multi-task AE model achieves the highest values in AUC (0.964), accuracy (0.821), precision (0.471), and F1 score (0.632), and the lowest value in FPR (0.206).ConclusionThe proposed multi-task AE model using two-dimensional (2D) feature maps can effectively detect anomalies in radiotherapy plans for lung cancer patients. Compared to the other existing AE models, the multi-task AE is more accurate and efficient. The proposed model provides a feasible way to carry out automated anomaly detection of VMAT plans in radiotherapy.

ABSTRACT: Herbal polysaccharides are extensively studied as vaccine adjuvants due to their safety and potent immunoenhancing activity. This study aimed to analyze the structure of Lagenaria siceraria (Molina) Standl polysaccharide (LSP50) and investigate its adjuvant activity for the H9N2 vaccine in broiler chickens. Structural analysis revealed that LSP50 primarily consisted of rhamnose, arabinose, xylose, mannose, glucose, and galactose with molar ratios of 23.12: 12.28: 10.87: 8.26: 2.64: 22.82 respectively. The adjuvant activity of LSP50 was evaluated, which showing significant enhancements compared to the H9N2 group. Parameters including the immune organ index, H9N2 specific IgG level, cytokines contents (IFN-γ, IL-2, IL-4, and IL-5), and the proportion of CD3e+CD8aT+cells were significantly increased in the LSP50 group (P < 0.05). Additionally, sequencing results showed that LSP50 modulates the immune response by regulating PLA2G12B and PTGDS genes involved in the arachidonic acid pathway. These findings were further validated through qPCR analysis to affirm the reliability of the sequencing data. In conclusion, our results demonstrate that LSP50 exhibits potent adjuvant activity, enhancing both cellular and humoral immunity.

ABSTRACT: Eggs are recognized for their rich nutrient profile, providing essential proteins and lipids with notable functional properties. This study examines the effects of incorporating Water Extract of Ampelopsis grossedentata (WEA) into poultry feed on egg quality, focusing on lipid content, choline, L-carnitine levels, and flavonoid compound deposition. Our results show significant increases in essential amino acids, flavonoids, and other bioactive compounds in eggs from WEA-treated hens, suggesting enhanced cardiovascular, antioxidant, and anti-inflammatory benefits. Additionally, we observed elevated levels of choline and betaine in egg yolks, alongside increased L-carnitine content, which may contribute to improved lipid metabolism and reduced cardiovascular disease risk. KEGG pathway analysis revealed upregulation of metabolites involved in critical metabolic pathways, enhancing the nutritional profile of eggs. Flavonoid compounds, traditionally associated with plant-based foods, were also significantly increased, with notable levels of 7, 4′-dihydroxyflavone, daidzein, and glycitein identified in WEA-treated eggs, indicating potential health benefits. These findings suggest that WEA supplementation can produce functional eggs with improved nutritional quality, offering a novel approach to enhancing egg production and meeting the growing demand for functional foods. Further research is needed to fully understand the bioavailability and health impacts of these enriched compounds.

Different sampling strategies produce varying sample data, serve as the primary input data and directly affect the accuracy of predictions in data-driven grid-based susceptibility models. This study analyzes the accuracy and variation of debris flow susceptibility maps (DFSMs) generated by various sampling strategies. The study area is the Yingxiu region in China, where six sampling strategies were applied, including three sampling locations (deposition area, runout area, and source area) and two sampling types (centroid and polygon) for the debris flow inventory. The effectiveness of 10 conditioning factors used to build the model was assessed by using Pearson correlation coefficient, variance inflation factor, and information gain ratio (IGR) techniques. We then used Weight of Evidence (WofE), Logistic Regression (LR), and Deep Neural Network (DNN) models to produce DFSMs and quantify their performance using the receiver operating characteristic curve (ROC), Accuracy (ACC), Precision, F1 score, and Recall. The results show that the WofE (AUC: 0.754–0.960), LR (AUC: 0.761–0.965), and DNN (AUC: 0.786–0.976) models all perform well, but the DFSMs and dominant factors depend strongly on sampling strategies, especially on sampling location. If the sample areas are excessively large and span across different factor class labels, or if there is a concentration of either large or small sample areas within a specific region, the results of centroid and polygon sampling strategies may differ or even be contradictory.We recommend: (1) determining sampling locations based on the research objectives to provide more accurate evaluation results; (2) selecting the sampling type by first considering the sample size. If the aforementioned conditions are not present, the quicker and more convenient centroid sampling strategy can be chosen; and (3) determining an appropriate sampling strategy and ensuring the accuracy of initial samples are paramount before producing DFSMs.

The monoclonal antibody rituximab improves clinical outcome in the treatment of CD20-positive lymphomatous neoplasms, and it is an established drug for treatment of these cancers. Successful mRNA COVID-19 (SARS-CoV-2) vaccination is extremely important for lymphoma patients because they tend to be elderly with comorbidities which leaves them at increased risk of poor outcomes once infected by Coronavirus. Anti-CD20 therapies such as rituximab, deplete B-cell populations and can affect vaccine efficacy. Therefore, a knowledge of the effect of COVID-19 vaccination in this group is critical. We followed a cohort of 28 patients with CD20-positive lymphomatous malignancies treated with rituximab that started prior to their course of COVID-19 vaccination, including boosters. We assayed for vaccine “take” in the humoral (IgG and IgA) and cellular compartment. Here, we show that short-term and long-term development of IgG and IgA antibodies directed toward COVID-19 spike protein are reduced in these patients compared to healthy controls. Conversely, the robustness and breath of underlying T-cell response is equal to healthy controls. This response is not limited to specific parts of the spike protein but spans the spike region, including response to the conserved Receptor Binding Domain (RBD). Our data informs on rational vaccine design and bodes well for future vaccination strategies that require strong induction of T-cell responses in these patients.

Since the survival of lymphoma patients who experience disease progression or relapse remains very poor, new therapeutic approaches and effective drugs are urgently needed. Here we show that auranofin (AF), an anti-rheumatoid drug thought to inhibit thioredoxin reductases (TXNRDs) as its mechanism of action, exhibited potent activity against multiple cancer types, especially effective against B cell lymphoma. Surprisingly, a knockdown of TXNRD1 and TXNRD2 did not cause significant cytotoxicity, suggesting that abrogation of TXNRD enzyme per se was insufficient to cause cancer cell death. Further mechanistic study showed that the interaction of AF with TXNRD could convert this antioxidant enzyme to a ROS-generating molecule via disrupting its electron transport, leading to a leak of electrons that interact with molecular oxygen to form superoxide. AF also suppressed energy metabolism by inhibiting both mitochondria complex II and the glycolytic enzyme GAPDH, leading to a significant depletion of ATP and inhibition of cancer growth in vitro and in vivo. Importantly, we found that the AF-mediated ROS stress could induce PD-L1 expression, revealing an unwanted effect of AF in causing immune suppression. We further showed that a combination of AF with anti-PD-1 antibody could enhance the anticancer activity in a syngeneic immune-competent mouse B-cell lymphoma model. Our study suggests that AF could be a potential drug for lymphoma treatment, and its combination with immune checkpoint inhibitors would be a logical strategy to increase the therapeutic activity.

Abstract A set of nozzle equipment for proton therapy is currently under development at China Institute of Atomic Energy (CIAE). To facilitate the off-line commissioning of the whole equipment, a set of ionization chamber signal generation system, known as the test electronics, was designed. The results showed that the system can simulate the beam position, beam fluence (which exhibits a positive correlation with the dose), and other related analog signals generated by the proton beam when it traverses the ionization chamber. Moreover, the accuracy of the simulated beam position is within ± 0.33 mm, and the accuracy of the simulated beam fluence signal is within ± 1%. The test electronics can output analog signals representing environmental parameters. The test electronics meets the design requirements, which can be used for the commissioning of the nozzle system as well as the treatment control system without the presence of the proton beam.

Abstract Background Postural abnormalities (PA) are common in the advanced stages of Parkinson’s disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. Methods T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. Results Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. Conclusions Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

As widely used energy-absorbing protective materials, the application of aluminum foam sandwich (AFS) panels remains constrained by the inherently low mechanical properties of the foam core. The incorporation of copper-coated carbon fibers (Cf) has proven to be effective in improving the mechanical properties of aluminum foam. Yet, the understanding of its foaming process and microstructure is still limited. In this work, AFS and Cf/AFS were fabricated by the packing rolling powder metallurgy method. The foaming behavior of AFS and Cf/AFS during elevated temperatures was in situ observed using synchrotron radiation X-ray imaging technology to investigate the effect of Cf on bubble nucleation, growth, and foam stability. Furthermore, the macroscopic pore size distribution, microscopic microstructure, and compressive mechanical properties of AFS and Cf/AFS were analyzed. The results showed that the existence of Cf greatly increases the nucleation rate, improves the foaming stability, and prevents the formation of localized abnormally large bubbles during the early nucleation and growth process. Meanwhile, Cf/AFS exhibited finer pore diameters and fewer pore defects than AFS. The distribution of Cf with excellent wettability along the pore wall prevented liquid film rupture and reduced coalescence. The compression experiment indicated that, in comparison to AFS, the compressive strength and energy absorption capacity of Cf/AFS have increased by approximately 40.6% and 84.8%, respectively.

Abstract Background Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. Results The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. Conclusion These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.

Abstract Background Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. Methods We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. Results The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. Conclusions The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Abstract Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

Abstract Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML.

Abstract Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of Kras G12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

Abstract This paper addresses the tracking control for an extended chained nonholonomic system under input saturation and matched disturbances. Specifically, the tracking error dynamic system is split into two subsystems in a cascade form. An integral sliding mode saturated controller is designed in combination with a finite‐time observer (FTDO) to ensure the finite‐time stability of the first subsystem, thereby simplifying the design of the second subsystem. A backstepping‐based adaptive saturated tracking control method is proposed for the second subsystem by incorporating the filter technology. The stability of the resulting closed‐loop system is demonstrated, and the tracking errors can be arbitrarily minimized through the appropriate design parameter selection. The effectiveness of the proposed scheme is validated through simulation and experimental results.

Objective Carbonate rocks have a significant carbon sink effect in water cycle. Since karst landforms are widely distributed in China, research on the potential of karst carbon sinks plays an important role in formulating regional strategies for increasing carbon sinks. Methods In this study, groundwater monitoring points in Hubei Province, which is located in the karst area of Southwest China, were selected. Quantitative calculations and method comparisons were performed based on the hydrochemical runoff method and the infiltration-equilibrium chemistry method. The spatial pattern and magnitude of karst carbon sinks in the hilly mountains of Hubei Province from 2019 to 2021 were evaluated via ArcGIS spatial analysis techniques. Additionally, the most suitable method for estimating karst carbon sinks at the regional scale were explored, the comprehensive analysis of the drivers of karst carbon sinks was performed, and the potential for increasing sinks were explored. Results The results showed that: (1) the intensity of carbon sinks estimated by the infiltration-equilibrium chemistry method were 2020>2019>2021. The total amount of karst carbon sinks in wet year (2020) was approximately 6 times of that in dry year (2019). The average annual carbon sink intensity in the three years was 12.84 t/(km2·a) and the annual total amount of carbon reached 163.89×104 t/a; (2) the infiltration-equilibrium chemistry method was more accurate in calculation results and simpler in data acquisition than the hydrochemical runoff method, and had a certain universality at both large and small spatial scales; (3) the change in carbon sinks was highly dynamic. The extent of changes in carbon sinks under climate change was mainly determined by runoff depth, with the intensity of carbon sinks increasing with runoff depth, while land use regulated the intensity of carbon sinks in karst processes; and (4) the karstification is strong in southwestern Hubei Province, so a pilot field of karst carbon sinks could be established within the area to quantitatively evaluate artificial interventions to increase carbon sinks. Conclusion This study not only provides an accurate and easy-to-use method for estimating karst carbon sinks, but also determines the magnitude and spatial pattern of karst carbon sinks in Hubei Province and figures out the coupling effect of the driving factors of carbon sink intensity, which demonstrates the complexity and anthropogenic control lability of karst carbon sinks. The results of this study provides a reliable scientific basis for the formulation of environmental protection policies and artificial sink increase measures.

Abstract Colon cancer is a common cancer with high mortality globally. The role of chondroitin polymerizing factor (CHPF) has been elucidated in various cancers. However, its role and mechanism remain unknown in colon cancer. CHPF expression was examined by GEPIA database, reverse transcription‐quantitative polymerase chain reaction and western blot. The relationship between CHPF expression and the clinicopathologic characteristics as well as miR‐214‐3p level was determined in colon cancer patients. The role and mechanism of CHPF in the growth, ferroptosis, and glycolysis of colon cancer cells were evaluated by cell counting kit‐8, biochemical detections, luciferase, and western blot experiments. Additionally, the role of CHPF was explored in xenografted mice. CHPF expression was increased and was related to advanced TNM stage, poor differentiation and shorter overall survival in patients with colon cancer. Knockdown of CHPF inhibited colon cancer cell growth, and downregulated the expression of proteins involving in ferroptosis and glycolysis both in vitro and in vivo. Besides, CHPF silencing increased the levels of ferrous iron and ROS, but decreased glucose uptake, lactate product, and ATP level in vitro. Mechanically, miR‐214‐3p directly targeted CHPF and negatively regulated its expression. Upregulation of miR‐214‐3p reduced cell viability, glucose uptake, lactate product, and ATP level, but increased the levels of ferrous iron and ROS, which were reversed by the overexpression of CHPF. Upregulation of CHPF predicted poor prognosis, and miR‐214‐3p/CHPF axis inhibited growth, downregulated the levels of glycolysis‐related indexes, and promoted ferroptosis in colon cancer cells.

A comparison was conducted on the microstructure, mechanical properties, and corrosion resistance of the fusion zone (FZ) in Zr R60702 laser lap joints prepared under air-cooled and water-cooled conditions. The results reveal that the upper and lower regions of the FZ in the welded joint consist of dendritic structure and α′ martensite, respectively. When water-cooled forced cooling is applied, α′ martensite emerges in the upper region of the FZ, with a few dendrites exhibiting an isoaxial distribution. Furthermore, the α′ martensite in the lower region becomes noticeably refined. The utilization of water-cooling triggers multiple strengthening mechanisms that, through synergistic interactions, enhance the microhardness, strength, and plasticity of the welded joints. The improved corrosion resistance within the FZ of the welded joint is attributed to the formation of a more stable passivation film.

Background In various disease contexts, magnesium abnormalities are associated with acute kidney injury (AKI) incidence. However, this association remains unclear and has not been systematically investigated in patients with cirrhosis. Hence, we aimed to elucidate the association between admission serum magnesium levels and AKI incidence in intensive care unit (ICU)-admitted cirrhotic patients.Methods A retrospective cohort study was conducted using MIMIC-IV2.2 data, focusing on critically ill patients with cirrhosis. We employed univariable and multivariable logistic regression and restricted cubic spline analyses to robustly address our research objectives. To further substantiate the findings, subgroup and sensitivity analyses were also conducted.Results Among the 3,228 enrolled ICU-admitted cirrhotic patients, 34.4% were female, and the overall AKI incidence was 68.6% (2,213/3,228). Multivariable logistic regression analysis revealed an independent relationship between elevated serum magnesium levels and increased AKI risk (OR = 1.55 [95% CI = 1.15–2.09], p = 0.004). Compared with individuals with serum magnesium levels < 1.6 mg/dL, individuals with serum magnesium levels in Q2 (1.6–2.6 mg/dL) and Q3 (≥2.6 mg/dL) had adjusted ORs for AKI of 1.89 (95% CI = 1.34–2.65, p 0.05).Conclusions High serum magnesium concentrations were significantly associated with an increased AKI risk in ICU-admitted patients with cirrhosis. Further randomized trials are needed to confirm this association.

Abstract Background and Aims Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death all over the world, and brings a heavy social economic burden especially in China. Several immuno‐combination therapies have shown promising efficacy in the first‐line treatment of unresectable HCC and are widely used in clinical practice. Nevertheless, which combination is the most affordable one is unknown. Our study assessed the cost‐effectiveness of the immuno‐combinations as first‐line treatment for patients with unresectable HCC from the perspective of Chinese payers. Methods A Markov model was built according to five multicenter, phase III, open‐label, randomized trials (Himalaya, IMbrave150, ORIENT‐32, CARES‐310, LEAP‐002) to investigate the cost‐effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A + B), sintilimab plus bevacizumab biosimilar (IBI305) (S + B), camrelizumab plus rivoceranib (C + R), and pembrolizumab plus lenvatinib (P + L). Three disease states were included: progression free survival (PFS), progressive disease (PD) as well as death. Medical costs were searched from West China Hospital, published literatures or the Red Book. Cost‐effectiveness ratios (CERs) and incremental cost‐effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. Results The total cost and quality‐adjusted life years (QALYs) of C + R, S + B, P + L, A + B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73, respectively, resulting in the most cost‐effective strategy of C + R with CER of $13,306.89 per QALY followed by S + B with CER of $24,072.86 per QALY. Compared with C + R, the ICER of S + B strategy was $70,725.38 per QALY, which would become the most cost‐effective when the willing‐to‐pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap‐002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. Conclusion As one of the promising immuno‐combination therapies in the first‐line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost‐effective strategy, which warranted further studies to best inform the real‐world clinical practices.

Metastatic colorectal cancer (mCRC) is characterized by significant phenotypic heterogeneity at the molecular level and presents a poor prognosis. Chemotherapy is commonly employed as the primary treatment option. Nevertheless, the advantages of chemotherapy are constrained, underscoring the critical necessity for novel treatment protocols aimed at enhancing patient outcomes. Human epidermal growth factor receptor 2 (HER2) has been recognized as a promising therapeutic target in mCRC. Pyrotinib, an innovative irreversible dual tyrosine kinase inhibitor targeting HER2, effectively inhibits cancer progression in various types of human cancers. Here, we present a case of a 39-year-old female with metastatic rectal cancer showing amplification of HER2. Despite resistance to multiple therapies, including trastuzumab and pertuzumab, the patient exhibited a remarkable therapeutic response to pyrotinib, tegafur combined with radiotherapy. This case provides evidence for the feasibility and potential efficacy of deploying pyrotinib in the salvage treatment of mCRC patients with HER2 amplification even though resistant to other anti-HER2 drugs.

ABSTRACT: Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple malignant behaviors by regulating cell cycle progression, tumor metastasis, and therapeutic response. Emerging evidence suggests that lncRNAs play a pivotal role in regulating the E2F1 pathway. This review aims to elucidate the intricate gene regulatory programs between lncRNAs and E2F1 in cancer progression. We elaborate on distinct mechanistic networks involved in cancer progression, emphasizing the potential of the lncRNAs/E2F1 axes as promising targets for cancer therapy. Additionally, we provide novel perspectives on current evidence, limitations, and future directions for targeting lncRNAs in human cancers. Fully deciphering the intricate network of lncRNA/E2F1-mediated regulatory mechanisms in cancer could facilitate the translation of current findings into clinical course, such efforts ultimately significantly improve the clinical prognosis of cancer patients.

Alternative splicing (AS) functions as a crucial program in transcriptional modulation, leading to proteomic diversity and functional alterations of proteins. These splicing actions induce various neoantigens that hold prognostic significance and contribute to various aspects of cancer progression, including immune responses against cancer. The advent of immunotherapy has remarkably revolutionized tumor therapy. In this regard, AS-derived neoantigens are potent targets for cancer vaccines and chimeric antigen receptor (CAR) T cell therapies. In this review, we outline that AS-derived neoantigens serve as promising immunotherapeutic targets and guide immunotherapy strategies. This evidence contributes to a deeper comprehension of the complexity of proteomic diversity and provides novel perspectives and techniques for precision medicine in immunotherapy. Moreover, we underscore the obstacles that are awaited to be addressed for this novel approach to become clinically applicable.

Studying rice water requirements (ETc) and area is crucial for developing irrigation schedules and adjusting crop structures. The cold rice cultivation region is China’s main high-quality rice production base and has the lowest temperature, highest latitude, and greatest sensitivity to climate. However, little research has focused on its past rice distributions and ETc, and its future variations are not yet clear. Past ETc was calculated by the Penman–Monteith and crop-corrected coefficient method, and past rice distribution patterns were analyzed based on the annual paddy rice planting area datasets. Future reference crop evapotranspiration (ET0) was projected by the statistical downscaling model (SDSM) based on the CMIP6 ensemble of daily predictor variables. The food and agriculture projections to 2050 datasets were used to project future rice areas, and the patch-generating land use simulation (PLUS) model simulated rice distribution. Finally, we projected future rice water supply demand. The results showed that ETc showed a decreasing trend, and the total rice area and production increased by 4.52 and 5.49 times from 1990 to 2020. Both in the past and future, rice was densely distributed in and expanded into the Sanjiang and Songnen Plains, and the spatial characteristic of ETc was as follows: the west was larger than the east, the north was larger than the south, and the central was in between. In the four future periods, the total ETc demonstrated an upward trend, increasing by 7.44–21.04, 15.64–34.74, 24.74–45.84, and 16.14–41.14 mm under the SSP126, SSP245, SSP370, and SSP585 scenarios, respectively, compared to the historical period. And it is generally ranked as SSP370 > SSP245 > SSP126. Finally, we projected future rice water supply meet the demand caused by rice area expansion.

Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that exhibits Ca2+ permeability. The TRPM2 channel is expressed in various tissues and cells and can be activated by multiple factors, including endogenous ligands, Ca2+, reactive oxygen species (ROS) and temperature. This article reviews the multiple roles of the TRPM2 channel in physiological and pathological processes, particularly on oxidative stress, inflammation and ischemia–reperfusion (I/R) injury. In oxidative stress, the excessive influx of Ca2+ caused by the activation of the TRPM2 channel may exacerbate cellular damage. However, under specific conditions, activating the TRPM2 channel can have a protective effect on cells. In inflammation, the activation of the TRPM2 channel may not only promote inflammatory response but also inhibit inflammation by regulating ROS production and bactericidal ability of macrophages and neutrophils. In I/R, the activation of the TRPM2 channel may worsen I/R injury to various organs, including the brain, heart, kidney and liver. However, activating the TRPM2 channel may protect the myocardium from I/R injury by regulating calcium influx and phosphorylating proline-rich tyrosine kinase 2 (Pyk2). A thorough investigation of the bidirectional role and regulatory mechanism of the TRPM2 channel in these physiological and pathological processes will aid in identifying new targets and strategies for treatment of related diseases.

Abstract Li−I2 batteries have attracted much interest due to their high capacity, exceptional rate performance, and low cost. Even so, the problems of unstable Li anode/electrolyte interface and severe polyiodide shuttle in Li−I2 batteries need to be tackled. Herein, the interfacial reactions on the Li anode and I2 cathode have been effectively optimized by employing a well‐designed gel polymer electrolyte strengthened by cross‐linked Ti–O/Si–O (GPETS). The interpenetrating network‐reinforced GPETS with high ionic conductivity (1.88 × 10−3 S cm−1 at 25°C) and high mechanical strength endows uniform Li deposition/stripping over 1800 h (at 1.0 mA cm−2, with a plating capacity of 3.0 mAh cm−2). Moreover, the GPETS abundant in surface hydroxyls is capable of capturing soluble polyiodides at the interface and accelerating their conversion kinetics, thus synergistically mitigating the shuttle effect. Benefiting from these properties, the use of GPETS results in a high capacity of 207 mAh g−1 (1 C) and an ultra‐low fading rate of 0.013% per cycle over 2000 cycles (5 C). The current study provides new insights into advanced electrolytes for Li−I2 batteries.

IntroductionThis study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows.MethodsA total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined.ResultsThere was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p