Search

Abstract Research on the improvement of national park recreation policies has attracted much attention to discrete choice experiments to obtain tourists’ preferences and willingness to pay. However, individual choice behavior is extremely complex, and the single Random Utility Maximization (RUM) model ignores anticipated regret and is insufficient to explain individuals’ actual choice behavior. To investigate whether regret influences tourists’ choices regarding the improvement of national park recreation attributes, this study introduces the Random Regret Minimization (RRM) model and explores the performance of polynomial logit models and hybrid latent class models in analyzing discrete choice models based on utility and regret. By constructing a hybrid utility-regret model, we examine how tourists trade off between attributes such as vegetation coverage, water clarity, amount of litter, and level of crowding in national park recreation. Results indicate that the RRM model has better goodness-of-fit and predictive ability than the RUM model, indicating that regret is a significant choice paradigm, and the hybrid model better explains respondents’ choices. Specifically, 62.5% of tourists’ choices are driven by regret, and regret-driven respondents are more inclined to increase vegetation coverage and improve water clarity, while utility-driven respondents are more inclined to reduce litter and crowding. This study not only provides a reference for managers to develop more optimal recreation improvement strategies but also offers theoretical insights for national park recreation improvement policies.

Abstract Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Abstract Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

This study was purposed to design a multimodal continuous optimization algorithm based on a scheme agent to address the multidimensional complexity of optimization. An evolutionary sampling method of subarea exploration and multiple exploitations was developed by employing the scheme with variable population size so as to obtain higher optimization speed and accuracy. Second, the distribution plan was quantified into high-dimensional variable parameters based on the characteristics of logistics distribution optimization problems, and a high-dimensional discrete optimization model was constructed. Then, we identified and addressed the prominent issues and malignant virtual changes in the application of continuous algorithms to discrete problems. We have introduced a reasonable mutation mechanism during the optimization sampling process to mitigate this issue. Continuous real coordinate points were transformed across the neighborhood to standard discrete integer coordinate points by normalizing and logicizing the optimization sampling coordinates; also, the discretization of the continuous algorithm was realized. This approach could effectively prevent the algorithm from searching for targets in continuous optimization space, thereby fully reducing the complexity of the objective function distribution after conversion. The experiments showed that the transformed multimodal discrete optimization algorithm effectively addressed the optimization design problem of logistics distribution.

Background The prevalence of atrial fibrillation (AF) in China is increasing year by year, and the prognosis and quality of life of patients urgently need attention. Current studies have confirmed that exercise rehabilitation is a beneficial way to improve the prognosis and poor quality of life in patients with AF after radiofrequency catheter ablation (RFCA). Adherence is a key measure of whether the benefits of exercise rehabilitation persist, but its trajectory remains unknown. Objective To examine the development trajectory and predictors of strength-duration adherence to home-based exercise rehabilitation among patients with AF after RFCA using five-period follow-up data based on prospective longitudinal observation. Methods Convenience sampling method was used to select 246 patients with AF who attended the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University for RFCA from May to November 2020 for follow-up. The baseline survey was conducted 1 week after enrollment, and the follow-up survey was conducted at 3, 6, 9 and 12 months after enrollment. The general and clinical data of patients were collected. The strength-duration adherence was monitored and recorded using smart devices or fitness log to assess exercise adherence in terms of strength-duration adherence; Self-efficacy for Exercise Scale (SEE), Fear of Activity in Patients with Chronic Heart Failure (Fact-CHF), Perceived Social Support Scale (PSSS), Patient Activation Measure 13 (PAM13) were used for assessing self-efficacy of exercise, fear of activity, social support and motivation level. Mplus tool was used to construct latent class growth model (LCGM), and the optimal fitting model was selected to determine the development trajectory of strength-duration adherence to home-based exercise rehabilitation among patients with AF after RFCA. Logistic regression analysis was used to identify the predictors of trajectory categories. Results A total of 202 patients were included in the final analysis with 44 patients lost to follow-up. The number of patients at baseline, 3 months, 6 months, 9 months, and 12 months after exercise were 202, 201, 185, 174 and 159, respectively, and the strength-duration adherence were (0.83±0.55), (1.07±0.54), (0.99±0.57), (0.91±0.55) and (0.89±0.60). The LCGM results showed group heterogeneity in the process of change in strength-duration adherence to exercise rehabilitation in patients, which was divided into 3 latent classes based on their development trajectories, including 69 in slow decline-low level group (34.2%), 14 in rapid increase-high level group (6.9%), and 119 in sustained adherence group (58.9%). Multinomial unordered Logistic regression showed higher levels of intensity-time adherence in the rapid increase-high level group and sustained adherence group using the slow decline-low level group as the reference group (P

Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70–80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model. Methods: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers. Results: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity. Conclusions: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study’s capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise.

The large-scale integration of wind power significantly alters the voltage dynamic characteristics of power systems. Wind turbines have a weak ability to withstand grid disturbances and have difficulty in providing effective reactive power support during transient periods. The sensitivity of wind turbines to the grid voltage significantly increases the probability of large-scale, cascading off-grid events. This paper proposes a coordinated control strategy to enhance the transient reactive power support capability of doubly fed wind farms. The additional stator current demagnetization control reduces the risk of a crowbar protection action after a fault and ensures that the unit power is controllable. Based on the voltage–reactive power coupling relationship, each unit can produce reactive power according to the voltage–reactive power sensitivity matrix during the transient period. After the reactive power output of the unit reaches the limit, transient active and reactive combined control is further adopted to reduce the active power output of the unit to a certain extent and improve the reactive power support capability. Finally, two cases are built in the PSCAD to verify the effectiveness of the proposed control strategy. The results show that the proposed control strategy can enable the wind farm to output more reactive power to the grid during the transient period, effectively supporting the system voltage during the transient process and avoiding further deterioration of the fault.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6–7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6–7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2–38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8–21.6) (p

ABSTRACT: CCAAT/enhancer binding protein zeta (C/EBPZ) was differentially expressed in abdominal adipose tissues of fat and lean broilers and regulated adipogenesis in chicken. The objective of this study was to elucidate the transcriptional regulation of C/EBPZ gene in chicken adipose tissue. A 2,031-base pair (bp) chicken C/EBPZ sequence (2,025 nucleotides upstream to 6 nucleotides downstream from the initiator codon, -2,025/+6) was studied. The sequence exhibited a significant promoter activity (P < 0.05) and had some cis-acting elements, notably, a core promoter was identified in nucleotides −94 to +6. Additionally, DNA pull-down assay showed that proteins interacted with chicken C/EBPZ promoter (−173/+6) in preadipocytes were implicated in transcription, post-transcriptional regulation and translation. In addition, KLF2 facilitated the activities of chicken C/EBPZ promoter (−2,025/+6, −1,409/+6, −793/+6, −485/+6, −173/+6, and −94/+6) in preadipocytes (P < 0.05). The expression levels of KLF2 and C/EBPZ in chicken abdominal adipose tissue were substantially associated (r = 0.5978278, P < 0.0001), and KLF2 increased C/EBPZ expression in vitro (P < 0.05). Additionally, chromatin immunoprecipitation (ChIP)-PCR analysis revealed that KLF2 has the ability to interact with the chicken C/EBPZ promoter regions at least at the positions −1,245/−1,048 and −571/−397. Mutation analysis showed that the CGCAGCGCCCG motif located in the chicken C/EBPZ promoter at positions -45 to -35 is involved in regulating transcription and facilitates trans activation by KLF2. These results provided some information of transcription control of C/EBPZ in chicken adipose tissue.

The correlation between the amount of organic carbon (OC) and sulfur (S) in sediments has been widely used as a paleosalinity indicator to distinguish between marine and freshwater environments. However, whether the ratio of total OC to total S (TOC/TS) can be used to identify unsteady or dynamic marine environments across sedimentary strata is still contended. An HZW1907 sediment core of 80 m in length was successfully collected in the middle of Hangzhou Bay (HZB), serving as one of the few boreholes that are crucial for the study of geologic and geo-environment changes in the coastal regions of eastern China since the Last Glacial Maximum (LGM). Total OC (TOC), stable carbon isotope, and TS of 82 subsamples from the HZW1907 core were analyzed to reconstruct the history of the shallow water biological pump and sulfur preservation record in the bay since the Late Pleistocene. Our results indicate that the samples had low concentrations of TOC (0.21%) and total nitrogen (TN) (0.02%), high mass ratio of TOC/TN (10.8), low δ13C (−24.9‰), low TS content (0.06%), and a high ratio of TOC/TS (9.1) from 33.6 ka BP to 12.3 ka BP, implying that freshwater organic matter (OM), algae, and C3 plant fragments were the main sources of OM in a relatively cold environment. The abundances of TOC, TN, and TS increased to 0.56%, 0.07%, and 0.4%, respectively, while δ13C (−23.9‰) increased and TOC/TS (2.7) decreased in the Holocene sediments, suggesting that seawater began to influence the composition of the sediments of HZB. Climate warming, which is likely to have impacted the results, was experienced from 12.3 ka BP. An OC isotope mixing model indicated that since the Mid-late Holocene, more than 70% of riverine OM accounted for the total OM. The TOC/TS ratio was identified as an effective indicator of seawater intrusion, with C/S ratios of 1–6 being considered to indicate a “sea–land transitional zone” sedimentary environment, a C/S >6 indicating freshwater, and a C/S

The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60-75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients' PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67-0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46-0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis.

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.

Background and objective: Mild cognitive impairment (MCI) is a cognitive dysfunction syndrome defined mostly by memory or other cognitive impairments, and may serve as a precursor to Alzheimer's disease (AD). In recent years, acupuncture has gained recognition as a potential intervention for MCI, attracting significant attention as a promising and well-established therapy. In this study, we critically evaluate the clinical efficacy and safety of an innovative acupuncture approach, termed “Kidney Nourishment and Spirit Regulation”, as a therapeutic modality for MCI in geriatric populations. Methods: A prospective, randomized, single-blind, placebo-controlled, single-center clinical trial design where patients will be allocated in acupuncture, placebo (sham acupuncture sessions), or blank for eight weeks. The blank group will receive health education over the same eight-week period and will be offered compensatory acupuncture therapy after this period. The selected acupoints for this investigation include GV20, EX-HN1, GV24, GV29, CV6, CV4, PC6, KI3, LI4, LR3, HT7 and SP6. The primary outcome measure will be the Montreal Cognitive Assessment (MoCA), while secondary outcomes include the Mini Mental State Examination (MMSE), Activity of Daily Living (ADL), and Electroencephalogram (EEG). Discussion: This study seeks to provide an optimum regimen for acupuncture therapy in elderly MCI patients and to provide considerable theoretical evidence for its popularization and future broad adoption. We thus postulate that the current trial data might enlighten and potentially guide future research in terms of study design refinement.

In order to solve the problem of multi-AGV path planning in a packaging workshop, this paper proposes a multi-AGV path-planning method based on time windows. A grid method is selected to build a map model. A penalty function is added to the A* algorithm to reduce the number of invalid turns made by AGVs during transportation. The AGV priorities are set according to the differences in AGV transport states. At the same time, the raster time window method is used to describe the five types of conflict that may occur in the process of multi-AGV transport. Combined with the AGV priorities, a multi-AGV anti-collision strategy is provided to realize the conflict-free path planning of multiple AGVs. The algorithm’s effectiveness was verified by simulation, and a reasonable quantity of AGVs was proposed based on AGV sensitivity analysis. The improved A* algorithm combined with the time window method can realize multi-AGV collision-free transportation and improve the efficiency and reliability of multi-AGV transportation.

Biodiversity plays important roles in ecosystem functions and genetic diversity is a key component of biodiversity. While effects of genetic diversity on ecosystem functions have been extensively documented, no study has tested how genetic diversity of plants influences greenhouse gas fluxes from plant-soil systems. We assembled experimental populations consisting of 1, 4 or 8 genotypes of the clonal plant Hydrocotyle vulgaris in microcosms, and measured fluxes of CO2 and CH4 from the microcosms. The fluxes of CO2 and CO2 equivalent from the microcosms with the 1-genotype populations of H. vulgaris were significantly lower than those with the 4- and 8-genotype populations, and such an effect increased significantly with increasing the growth period. The cumulative CO2 flux was significantly negatively related to the growth of the H. vulgaris populations. However, genotypic diversity did not significantly affect the flux of CH4. We conclude that genotypic diversity of plant populations can influence CO2 flux from plant-soil systems. The findings highlight the importance of genetic diversity in regulating greenhouse gas fluxes.

Background: Herbal medicine as complementary ways are needed for patients who refuse to take medicine for life. Early intervention and lifestyle could delay the time of taking drugs. Objective: To assess the efficacy of XiaokeGranules vs Sitagliptin in patients who diagnosed T2D. Methods: This is a randomized, double-blind trial. T2D patients were randomly assigned in a 1:1 ratio to Xiaoke Granules and Sitagliptin(50 mg), an anti-diabetic medicine group, for 12 weeks. Before randomization, the consenting participants were subjected to 2 weeks of screening, followed by twelve weeks of intervention. The primary outcome was change from baseline in glycosylated haemoglobin (HbA1C) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) calculation at 12 week. Results: We recruited 103 patients, 84 patients participated in the clinical trial and finally 79 patients finished., the least square mean change in HbA1c and HOMA-IR from baseline was similar in both groups, in which HbA1c (6.93 ± 0.76, P = 0.007) and 2hPG (10.87 ± 2.20, P = 0.016) for the Control group, and HbA1c (6.76 ± 0.67, P

Organophosphine compounds have broad application prospects in industrial production and daily life. Their flexible polar and nonpolar groups make them have adjustable properties. There are many kinds of organic phosphine compounds and their derivatives, and their physical and chemical properties are also different, which makes organic phosphine compounds more and more widely used in production and life, especially in beneficiation and metallurgy. This paper lists some organic phosphine agents that have obtained good data in laboratory test or excellent performance in industrial application, and some representative phosphorus compound beneficiation and metallurgy reagents. Referring to some current research results and combined with production practice, this paper makes a specific classification research on them, and looks forward to their future development and application trend.

ABSTRACT Porcine epidemic diarrhea virus (PEDV) is the main etiologic agent causing acute swine epidemic diarrhea, leading to severe economic losses to the pig industry. PEDV has evolved to deploy complicated antagonistic strategies to escape from host antiviral innate immunity. Our previous study demonstrated that PEDV downregulates histone deacetylase 1 (HDAC1) expression by binding viral nucleocapsid (N) protein to the transcription factor Sp1, inducing enhanced protein acetylation. We hypothesized that PEDV inhibition of HDAC1 expression would enhance acetylation of the molecules critical in innate immune signaling. Signal transducer and activator of transcription 1 (STAT1) is a crucial transcription factor regulating expression of interferon (IFN)-stimulated genes (ISGs) and anti-PEDV immune responses, as shown by overexpression, chemical inhibition, and gene knockdown in IPEC-J2 cells. We further show that PEDV infection and its N protein overexpression, although they upregulated STAT1 transcription level, could significantly block poly(I·C) and IFN-λ3-induced STAT1 phosphorylation and nuclear localization. Western blotting revealed that PEDV and its N protein promote STAT1 acetylation via downregulation of HDAC1. Enhanced STAT1 acetylation due to HDAC1 inhibition by PEDV or MS-275 (an HDAC1 inhibitor) impaired STAT1 phosphorylation, indicating that STAT1 acetylation negatively regulated its activation. These results, together with our recent report on PEDV N-mediated inhibition of Sp1, clearly indicate that PEDV manipulates the Sp1-HDAC1-STAT1 signaling axis to inhibit transcription of OAS1 and ISG15 in favor of its replication. This novel immune evasion mechanism is realized by suppression of STAT1 activation through preferential modulation of STAT1 acetylation over phosphorylation as a result of HDAC1 expression inhibition. IMPORTANCE PEDV has developed sophisticated evasion mechanisms to escape host IFN signaling via its structural and nonstructural proteins. STAT1 is one of the key transcription factors in regulating expression of ISGs. We found that PEDV and its N protein inhibit STAT1 phosphorylation and nuclear localization via inducing STAT1 acetylation as a result of HDAC1 downregulation, which, in turn, dampens the host IFN signaling activation. Our study demonstrates a novel mechanism that PEDV evades host antiviral innate immunity through manipulating the reciprocal relationship of STAT1 acetylation and phosphorylation. This provides new insights into the pathogenetic mechanisms of PEDV and even other coronaviruses.

Background: The sparsity of head-to-head trials for medications used as in atopic dermatitis (AD) treatment makes therapy options difficult. Objective: To better compare the efficacy and safety of abrocitinib and upadacitinib with dupilumab in patients with moderate-to-severe AD. Methods: We systematically searched MEDLINE, EMBASE, and the Cochrane Library database for head-to-head trials. Results: Three studies with 2256 patients were included. The analysis revealed that improvement of EASI-75 was rapidly registered with abrocitinib/upadacitinib as compared to the dupilumab, even as early as week 2 of treatment. The proportions of patients who reached the endpoint of EASI-75 at week 12 and end of therapy were also higher in the abrocitinib/upadacitinib group. Significant improvement in EASI-90 scores was demonstrated with abrocitinib/upadacitinib at week 2 and at all subsequent time points. The administration of abrocitinib/upadacitinib provided a faster onset of IGA response at week 2. The differences in IGA response remained significant at week 12 and end of therapy. Compared with dupilumab, a larger proportion of patients treated with abrocitinib/upadacitinib achieved early itch relief at 2 weeks. Better results were found later during treatment, in between the 12 weeks to the end of study in abrocitinib/upadacitinib group. The only observed significant result of adverse events were severe adverse events between the abrocitinib/upadacitinib group (n = 40) and the dupilumab group (n = 24) (p = 0.043). TEAEs of any causality that led to treatment discontinuation and serious adverse events have not shown special risks in the patients treated with abrocitinib/upadacitinib. Conclusions: This study demonstrated that anti-JAK therapy, particularly abrocitinib and upadacitinib, exhibited superiority over dupilumab in achieving fast relief of disease signs with an acceptable safety profile in patients with moderate-to-severe atopic dermatitis.

Under the backdrop of the “double-carbon” target, the primary grain-producing regions in China are confronted with the tasks of mitigating pollution and carbon emissions and ensuring food security. This paper explores the eco-efficiency of cropland utilization and the factors influencing the primary grain-producing regions in China, utilizing panel data from 13 provinces spanning the period from 2000 to 2019. The analysis employs three models: the super-efficiency SBM model, the Malmquist index model, and the random-effect panel Tobit model. The findings suggest the following: (1) Although the eco-efficiency of cropland utilization in China’s primary grain-producing regions did not reach the production frontier during the period of 2000–2019, it exhibited a high level with an overall upward trend. The limiting factor inhibiting the growth of total factor productivity is lower technical efficiency. (2) There is evident spatial variation in the eco-efficiency of cropland utilization across China, displaying a dynamic evolution from northeast > western > central > eastern to northeast > western > eastern > central. Total factor productivity in each province demonstrates an upward trend, with the east > northeast > west > central ranking. (3) Regarding the influencing factors, the utilization of agricultural production chemicals exerts a negative influence, while the proportion of government financial input, labor input, and irrigation index have a positive impact.

Abstract Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.

Abstract An advance Li‐sphere possessing a definitely regular morphology in Li deposition enables a well‐defined more robust structure and superior solid‐electrolyte interphase (SEI) to achieve high‐efficiency long‐term cycles in Li metal anode. Here, a new sight of high Li+ cluster‐like solvation sheaths coordinated in a localized high‐concentration NO3− (LH‐LiNO3) electrolyte fully clarifies for depositing advanced Li spheres. Moreover, we elucidate a critical amorphous‐crystalline phase transition in the nanostructure evolution of Li‐sphere deposits during the nucleation and growth. Li‐sphere anode exhibits ultra‐stable structural engineering for suppressing Li dendrite growths and rendering ultralong life of 4000 cycles in symmetrical cells at 2 mA cm−2. The as‐constructed Li spheres/3DCM|LiFePO4 (LFP) full cell delivers a high capacity retention of 90.5% at 1 C after 1000 cycles, and a robust dendrite‐free structure also stably exists in Li‐sphere anode. Combined with high‐loading LFP cathodes (6.6 and 10.9 mg cm−2), superb capacity retentions are up to 96.5% and 92.5% after 800 cycles at 1 C, respectively. Cluster‐like solvation sheaths with high Li+ coordination exert significant influence on depositing a high‐quality Li‐sphere anode.

BackgroundMedical students suffer more pressure due to various reasons and their mental health problems get more attention. Resilience is a positive psychological perspective to explore the medical students’ mental health and coping style problems. This study focuses on the medical students in school and uses the method of latent category analysis (LCA) to analyze the classification characteristics of their resilience. Therefore, the study aims to help psychological educators in medical colleges to develop positive mental health education strategies for medical students.ObjectiveTo explore the potential categories of resilience of medical students and the relationship between these categories and mental health and coping style.MethodsA total of 1,457 medical students from four medical colleges in Anhui Province were selected as the research subjects by a convenience sampling method. A general information questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), Kessler 10 and the Simplified Coping Style Questionnaire (SCSQ) were used to investigate; SPSS 25.0 and Mplus 7 software were used for basic analysis and latent category exploration.Expected resultsThe medical students were divided into three potential categories of mental resilience: the low resilience group, moderate resilience self-improvement group and high resilience tough group. The optimism dimension level of the three categories was low. There were statistically significant differences in the distribution of resilience among medical students, such as gender, source of students, and paternal and maternal education level. There were significant differences in the mental health, positive coping style and negative coping style scores among the three categories. Female medical students with low parental education levels have a lower level of resilience. Logistic regression analysis showed that a lower maternal education level was a risk factor for resilience level, and a high positive coping style score and gender were protective factors for resilience level.DiscussionThere are group differences in the resilience of medical students, which suggests that school health workers should formulate targeted intervention programs for different types of students to improve their resilience and mental health, and further more, this study reminds mental health workers in colleges and universities to pay more attention to the mental health status of female medical students whose parents are less educated.

Abstract Preparation of non‐conjugated luminescent polymers (NCLPs) with excellent cluster luminescence (CL) performance is of great significance for scientific and industrious applications, and yet improving the performance of NCLPs through proper structural design is still a huge challenge. Herein, we report a non‐conjugated ionized polymeric system consisting of (−)‐camphorsulfonic acid ((−)‐CSA) and poly(2‐vinylpyridine) (P2VP). These acid‐base complexes exhibit typical excitation‐dependent fluorescence and room‐temperature phosphorescence (RTP) with a lifetime up to 364 ms. We discover that changing the stereoregularity from atactic to isotactic significantly improves the CL performance of the complex. It (1) broadens the fluorescence emission spectra to cover the entire visible region, (2) enhances the fluorescence emission intensity at long wavelength beyond 500 nm, (3) enhances the phosphorescence intensity, and (4) extends the phosphorescence lifetime. Systematical experimental characterization and molecular dynamics simulation unravel the key role of stereoregularity in determining the formation of different pyridine aggregates that strongly influence the CL performance. Moreover, the different luminescence shows great potential in excitation divided information display and time‐resolved encrypted display. This work not only points to a new direction for developing NCLPs with excellent performance, but also broadens the applications of NCLPs materials.

Abstract Porcine epidemic diarrhea virus (PEDV) can infect pigs of all ages, especially piglets. PEDV has spread across Asia since the 1980s. The highly virulent variant PEDV broke out on a large scale and caused huge economic losses to the pig industry in late 2010 in China. Rapid detection methods with high specificity and sensitivity are urgently needed for the diagnosis and control of the disease. In this study, we divided the PEDV S1 gene into three segments and constructed the recombinant plasmids pFastBac1-S1T1 (aa 21–279), pFastBac1-S1T2 (aa 280–539) and pFastBac1-S1T3 (aa 540–788), which carry the different antigenic regions of the S1 gene. Truncated S1 proteins PEDV-S1T1/S1T2/S1T3 were obtained by a Bac-to-Bac expression system, with protein sizes of 36 kDa, 38 kDa and 38 kDa, respectively. Recombinant proteins presented high reactivity with the monoclonal antibody against PEDV and positive pig serum. Based on full-length S1 protein and these truncated proteins, we established indirect ELISA methods for the detection of PEDV IgA antibody. A total of 213 clinical serum samples were tested by the above indirect ELISA methods, and IFA was used as the gold standard. ROC curves revealed a significant correlation between S1-ELISA and S1T2-ELISA with a 0.9134 correlation coefficient and favourable sensitivity and specificity of S1-ELISA (93.24%, 95.68%) and S1T2-ELISA (89.33%, 94.16%). Our results also indicated that serum with higher neutralizing activity (SNT ≥ 40) had a higher IgA antibody level based on S1-ELISA, S1T1-ELISA and S1T2-ELISA. In conclusion, both S1-ELISA and S1T2-ELISA can be used as candidate systems for detecting anti-PEDV IgA antibody titers in serum, which can reflect the level of neutralizing activity in pigs after natural infection or vaccination. The above research results provide a basis for the prevention and control of PEDV and can be used in the detection of host anti-infective immunity and evaluation of vaccine immune effects.

Northwest Zhejiang area (NWZJ) is one of the important parts of the large Qingzhou-Hangzhou mineralized belt in South China formed during the Late Jurassic–Early Cretaceous period. Through the study of zircon LA-ICPMS U-Pb dating, whole-rock geochemistry, and Sr-Nd isotopes for the Wujinshan granitoid in NWZJ, two distinct S-type granitic rocks of porphyry type granodiorite and granite were identified, and the two ages of 146.4 ± 1.5 Ma for granodiorite porphyry and 141.9 ± 1.4 Ma for granite porphyries were obtained. These rocks exhibited a geochemical affinity for S-type granitoid, and the two magmatic ages indicate that these rocks were intruded in two magmatic pulses. The Late Jurassic granodiorite porphyry showed moderate SiO2 (64.38–67.89 wt.%) with higher K2O + Na2O (6.22–6.78 wt.%), lower K2O/Na2O (0.57–0.96), moderate Zr (170–215 ppm), high Sr (302–475 ppm), and low Mg# (31–32) contents. The Early Cretaceous granite porphyries contained high SiO2 (69.68–74.85 wt.%), variable K2O + Na2O (4.60–6.99), high K2O/Na2O (1.72–23.53), slightly higher Zr (160–255 ppm), variable Sr (25–412 ppm), and very low to intermediate Mg# (13–44). The granodiorites had intermediate ∑REE (149–177 ppm), while granite samples showed moderate to high ∑REE content (147–271 ppm), and both rocks showed negative Eu anomalies (0.18–0.29). We propose that these two rocks were predominantly generated by the partial melting of Mesoproterozoic metamorphic basement and underwent variable degrees of fractionation and evolution. The Late Jurassic granodiorite porphyry was formed by the partial melting of Mesoproterozoic metamorphic basement with slab-derived melts or basaltic lower crust input following fractional crystallization, while the Early Cretaceous granite porphyries were generated by the partial melting of Mesoproterozoic metamorphic basement and crystal fractionation with variable magma mixing and assimilation in the upper crust. Tectonically, the Wujinshan granitoid formed in a volcanic arc setting largely affected by the subduction and slab rollback of the paleo-Pacific Plate.

The high‐order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi‐omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase‐sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI‐rich and CGI‐poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional‐level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer‐related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity.

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Plant-soil feedbacks (PSFs) may vary among genotypes within the same species and may also be predicted by plant functional traits. So far, however, it is still unclear whether PSFs can be correlated with plant functional traits across genotypes of the same species. We conducted a two-phase PSF experiment with a clonal plant Hydrocotyle vulgaris. In the conditioning phase, we planted 12 genotypes of H. vulgaris separately in the soil. In the feedback phase, all these genotypes of H. vulgaris were grown again separately in each of the conditioned soil that was trained either by the same genotype (home soil) or by the other 11 genotypes (non-home soil). Most of the genotypes showed negative PSFs, as indicated by significant lower biomass and number of ramets in the home soil than in the non-home soil. However, there were also genotypes showing neutral PSFs as neither biomass nor number of ramets differed significantly between the home and the non-home soil or positive PSFs as biomass and number of ramets were higher in the home than in the non-home soil. In addition, we found a significant positive relationship between the PSF strength with lamina area, specific lamina area, petiole length, specific petiole length and internode length, but a negative relationship between the PSF strength and specific internode length. We conclude that the PSFs can vary among genotypes within the same species and negative PSFs are more common compared to positive PSFs. The results also highlight the role of plant functional traits in predicting PSFs across genotypes.

Background Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.