Search

Abstract Accurate and fast histological diagnosis of cancers is crucial for successful treatment. The deep learning-based approaches have assisted pathologists in efficient cancer diagnosis. The remodeled microenvironment and field cancerization may enable the cancer-specific features in the image of non-cancer regions surrounding cancer, which may provide additional information not available in the cancer region to improve cancer diagnosis. Here, we proposed a deep learning framework with fine-tuning target proportion towards cancer surrounding tissues in histological images for gastric cancer diagnosis. Through employing six deep learning-based models targeting region-of-interest (ROI) with different proportions of no-cancer and cancer regions, we uncovered the diagnostic value of non-cancer ROI, and the model performance for cancer diagnosis depended on the proportion. Then, we constructed a model based on MobileNetV2 with the optimized weights targeting non-cancer and cancer ROI to diagnose gastric cancer (DeepNCCNet). In the external validation, the optimized DeepNCCNet demonstrated excellent generalization abilities with an accuracy of 93.96%. In conclusion, we discovered a non-cancer ROI weight-dependent model performance, indicating the diagnostic value of non-cancer regions with potential remodeled microenvironment and field cancerization, which provides a promising image resource for cancer diagnosis. The DeepNCCNet could be readily applied to clinical diagnosis for gastric cancer, which is useful for some clinical settings such as the absence or minimum amount of tumor tissues in the insufficient biopsy.

Abstract The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance. SRC activates hexokinase2 which up-regulates glycolysis and especially the pentose phosphate pathway that leading to increased nucleotide synthesis and NADPH production which can neutralize reactive oxygen species (ROS) induced by cisplatin, thereby protecting bladder cancer cells from cisplatin-induced DNA damage. This phenomenon was effectively reversed by knockout of SRC and inhibition of SRC activity by the SRC inhibitor, eCF506. Moreover, we constructed Cell-derived xenograft (CDX) and Patient-derived xenograft (PDX) from cisplatin-resistant bladder cancer patient. eCF506 exhibited excellent anti-tumor effects and effectively enhanced cisplatin-sensitivity. Altogether, our findings demonstrate that targeting SRC is a promising approach to overcome cisplatin-resistance in bladder cancer, and providing new insights for combination therapy in bladder cancer.

Abstract Significant progress has been made in the development of potential therapies for diseases associated with inflammation and oxidative stress. Nevertheless, the availability of effective clinical treatments remains limited. Herein, we introduce a novel silk-based bioactive material, TPSF, developed by sequentially conjugating Tempol and phenylboronic acid pinacol ester to silk fibroin. This innovative reactive oxygen species (ROS) scavenging material not only effectively eliminates free radicals and hydrogen peroxide but also readily self-assembles into nanoparticle forms (TPSN). In vitro experiments have demonstrated that TPSN exhibits significant anti-inflammatory activities and cytoprotective effects against ROS-mediated damage. Consistently, in murine models of acute lung and kidney injury, TPSN outperforms the small-molecule antioxidant NAC, exhibiting superior therapeutic efficacy. Mechanistically, TPSN has the capability to reprogram M1-like macrophages toward an M2-like state. Importantly, biocompatibility assays confirm that TPSN has good safety profiles. Consequently, TPSN, characterized by its favorable protective effects and excellent biocompatibility, exhibits considerable promise as a therapeutic intervention for inflammation-related diseases. This innovative strategy, which incorporates multifunctional antioxidant components into the silk fibroin matrix, effectively addresses oxidative stress and acute inflammation. Furthermore, it highlights the potential of modified silk fibroin materials in the management and mitigation of inflammation-led tissue damage.

Intervertebral disc degeneration (IVDD) is a leading cause of discogenic low back pain, contributing significantly to global disability and economic burden. Current treatments provide only short-term pain relief without addressing the underlying pathogenesis. Herein we report engineering of biomimetic therapies for IVDD guided by single-cell RNA-sequencing data from human nucleus pulposus tissues, along with validation using animal models. In-depth analyses revealed the critical role of mitochondrial dysfunction in fibrotic phenotype polarization of nucleus pulposus cells (NPCs) during IVDD progression. Consequently, mitochondrial transplantation was proposed as a novel therapeutic strategy. Transplanted exogeneous mitochondria improved mitochondrial quality control in NPCs under pathological conditions, following endocytosis, separate distribution or fusion with endogenous mitochondria, and transfer to neighboring cells by tunneling nanotubes. Correspondingly, intradiscal mitochondrial transplantation significantly delayed puncture-induced IVDD progression in rats, demonstrating efficacy in maintaining mitochondrial homeostasis and alleviating pathological abnormalities. Furthermore, exogenous mitochondria were engineered with a bioactive, mitochondrial-targeting macromolecule to impart anti-oxidative and anti-inflammatory activities. The obtained multi-bioactive biotherapy exhibited significantly enhanced benefits in IVDD treatment, in terms of reversing IVDD progression and restoring structural integrity through the mtDNA/SPARC-STING signaling pathways. Overall, our engineered mitochondrial therapies hold great promise for treating IVDD and other musculoskeletal diseases linked to mitochondrial dysfunction.

Abstract Background High levels of high-density lipoprotein cholesterol (HDL-C) are previously considered protective against cardiovascular diseases (CVD), but recent studies suggest an increased risk of adverse events at very high HDL-C levels in the general population. It remains to be elucidated such a relationship in diabetes, a condition with high cardiovascular risks. We examined the association of HDL-C levels with the risk of major adverse cardiovascular events (MACE) and mortality in type 2 diabetes. Methods This retrospective cohort study identified individuals with type 2 diabetes who had HDL-C records (2008–2020) from the electronic health record database of the Hong Kong Hospital Authority. They were classified into three groups based on their first-recorded HDL-C levels following diabetes diagnosis: low (≤ 40 mg/dL), medium (> 40 and ≤ 80 mg/dL) and high HDL-C (> 80 mg/dL) groups. The primary outcome was incident MACE (composite of myocardial infarction, stroke, heart failure, and cardiovascular mortality). Cox regression model and restricted cubic spline analysis were employed to assess the relationship between HDL-C and adverse outcomes. Results Among 596,943 individuals with type 2 diabetes included, 168,931 (28.30%), 412,863 (69.16%), and 15,149 (2.54%) were classified as low HDL-C, medium HDL-C, and high HDL-C groups, respectively. Over a median follow-up of 79.5 months, both low and high HDL-C groups had higher risk of incident MACE compared to the medium HDL-C group (HR 1.24, 95% CI 1.23–1.26, P

Abstract Background This study aims to evaluate the 5-year impact of a Health Empowerment Program (HEP) on mitigating problematic conducts and enhancing the health-related quality of life (HRQOL) among children living in poverty. Methods A prospective cohort study (N = 239, Intervention group: n = 124, Comparison group: n = 115) was established with participants recruited between July 2013 and March 2016 and followed until November 2021. During the 5-year study period, children and their parents from the intervention group were invited to join a multi-dimensional HEP. At baseline and follow-up, both intervention and comparison groups were assessed using the Chinese Strengths and Difficulties Questionnaire (SDQ) and Chinese Child Health Questionnaire Parent Form 28 (CHQ-PF28). Multiple linear regressions were conducted to identify changes in outcome variables as the effect of the HEP. Results Upon completion of the 5-year follow-up, children in the intervention group showed a larger decline in conduct problems (B = − 0.66, p

Abstract Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants within joint genomic loci shared between PCOS and T-related traits. Functional annotations suggested that these variants might impact PCOS by modulating nearby genes, such as FSHB. Our findings support the hypothesis that PCOS is significantly influenced by androgen abnormalities. Additionally, this study identified several causal variants potentially involved in shared biological mechanisms between PCOS and T regulation.

Dysfunction of keratinocytes affects diabetic wound healing, but underlying mechanisms have not been understood. This study examines crotonylation's role in ferroptosis and autophagy in keratinocytes, particularly regarding ACSL4, using STZ-induced diabetic rats and high glucose-exposed keratinocytes to assess these processes. The ACSL4 knockdown was achieved using adenovirus in wounds to examine the impact of ferroptosis modulation on healing diabetic wounds. MB-3 was utilized to block the H3K27 crotonylation (H3K27cr) in order to clarify the regulatory function of crotonylation in both autophagy and ferroptosis. In STZ-induced diabetic skin and high glucose-exposed keratinocytes, ferroptosis mediated by ACSL4 and suppression of autophagic flux were demonstrated. Moreover, the downregulation of ACSL4 triggered ferroptosis in adjacent wounds of diabetic rats and improved wound healing. The degradation of ACSL4 may be observed via the autophagy-lysosome pathway in keratinocytes. Downregulation of SQSTM1 in diabetic keratinocytes leads to autophagy inhibition and modulates the protein level of ACSL4. Mechanistically, total crotonylation levels and H3K27cr were remarkably elevated in the skin and keratinocytes of diabetic rats; blocking high glucose-induced H3K27cr with MB-3 can enhance SQSTM1 transcription and expression while promoting autophagy and reducing ACSL4-induced ferroptosis in keratinocytes. Therefore, H3K27cr influences autophagy by adjusting SQSTM1 to facilitate ACSL4-triggered ferroptosis in diabetic keratinocytes. This study clarifies the relationships between acylation modifications, autophagy, and ferroptosis, while also offering mechanistic insights and potential therapeutic targets for issues associated with diabetic wound healing.

Abstract Neuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury‐induced neuropathic pain is first established to explore its pathophysiological characteristics. Recognizing the role of neuroinflammation, an inflammation‐resolving amphiphilic conjugate PPT is designed and synthesized by simultaneously conjugating polyethylene glycol, phenylboronic acid pinacol ester, and Tempol onto a cyclic scaffold. PPT can self‐assemble into nanomicelles (termed PPTN). Following intravenous injection, PPTN preferentially accumulates in the injured nerve, ameliorates the neuroinflammatory milieu, and promotes nerve regeneration, thereby shortening neuropathic pain duration in rats. Moreover, the Ca2+ channel α2δ1 subunit is identified as a therapeutic target by RNA‐sequencing analysis of the injured nerve. Based on this target, a mimicking peptide (AD peptide) is screened as an analgesic. By packaging AD peptide into PPTN, a combination nano‐analgesic APTN is developed. Besides potentiated anti‐hyperalgesic effects due to site‐specific delivery and on‐demand release of AD peptide at target sites, APTN simultaneously inhibits neuroinflammation and promotes nerve regeneration by reprogramming macrophages via regulating MAPK/NF‐kB signaling pathways and NLRP3 inflammasome activation, thus affording synergistic efficacies in treating nerve injury‐induced neuropathic pain.

PurposeChinese Visceral Adiposity Index (CVAI) has been found significantly associated with hypertension in general and type-2 diabetes adults. However, the predictive value of CVAI for the incidence of hypertension in adults with prediabetes is unclear. This study aimed to assess the predictive utility of the CVAI for the new onset of hypertension in middle-aged and older adult Chinese individuals with prediabetes.MethodsA prospective cohort study was conducted involving participants aged 45 years and above with prediabetes from the 2011–2012 cohort of the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression models were utilized to investigate the association between CVAI levels and the risk of new-onset hypertension.ResultsThe study included 2,186 participants, among whom 444 (20.31%) developed hypertension. Significantly higher incidence rates of hypertension were observed in individuals belonging to the highest quartile group (Q4) compared to those in the lowest quartile group (Q1) of CVAI (29.41% vs. 14.69%, p

ObjectiveThis network meta-analysis was to compare the efficacy of different drugs on cardiac function, renal function, and clinical outcomes in patients with acute heart failure (AHF) accompanied by renal dysfunction.MethodsPubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of AHF between January 1st 2001 and March 31th 2024. The primary outcome measures were N-terminal pro-B type natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), glomerular filtration rate (GFR), blood urea nitrogen, serum creatinine, all-cause mortality within 60 days, and cardiovascular mortality.ResultsAfter screening 30,697 citations, 13 studies (21,745 patients) were included, and drugs including nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, and spirolactone, and high dose of diuretics (HDD, furosemide, and spirolactone) were estimated. The results indicated that HDD had the best efficacy in reducing NT-proBNP levels. In detail, HDD notably reduced NT-proBNP levels compared to conventional treatment or placebo (PLC) [MD = −950.24; 95% CrI (−1,832.21, −64.12)]. Levosimendan significantly increased GFR levels compared to PLC [MD = 14.46; 95% CrI (3.88, 25.97)] and tolvaptan [MD = 13.83; 95% CrI (2.31, 25.33)]. No significant difference was found in 60-day all-cause mortality and cardiovascular mortality across drugs.ConclusionHDD showed the best efficacy in reducing NT-proBNP levels compared with dopamine and nesiritide, and levosimendan could significantly improve GFR levels, with no marked difference in the effect of various drugs on 60-day all-cause mortality. Hence, HDD and levosimendan may be optimal agents in the treatment of AHF with renal dysfunction.Systematic Review RegistrationPROSPERO, identifier (CRD42023454616).

A mounting number of studies have been documenting strong pro-inflammatory and pro-fibrotic effects of carbon nanotube (CNT). However, the molecular mechanisms of single-walled CNT (SWCNT)-provoked lung injury remain to be elucidated. Here, we established a mice model of SWCNT-induced lung injury by intratracheal instillation and found that C5a-C5a receptor-1 (C5aR1) signaling was significantly activated along with abundant neutrophils recruitment in lungs at early phase post SWCNT administration, which were positively correlated with early lung inflammation and late pulmonary fibrosis. C5a-C5aR1 signaling activation and neutrophils recruitment were subsequently decreased in a time-dependent manner. Furthermore, inhibition of C5a-C5aR1 axis with C5aR1 antagonist PMX205 treatment not only dramatically reduced neutrophils recruitment and inflammatory cytokines secretion at early phase, but also effectively alleviated early lung inflammation and late pulmonary fibrosis induced by SWCNT exposure. In conclusion, our study provides novel insights into the underlying biological mechanism that C5a-C5aR1 axis regulates neutrophils recruitment-mediated lung injury induced by SWCNT, may help to develop therapeutic strategies for SWCNT-provoked lung injury.

Abstract Inulin, a polysaccharide predominantly composed of fructose molecules, possesses a linear chain structure with β-(2 → 1) linkages between fructose units and usually has a glucose molecule at one end of the chain. It is not only an edible natural functional polysaccharide, but also a soluble dietary fiber, with a variety of physiological functions such as antioxidant, promoting the growth of gut flora and maintaining its homeostasis, enhancing gut immune function, promoting nutrient absorption, lowering glycemia, as well as providing anti-carcinogenic, weight loss and constipation relief. This review provides a comprehensive overview of the latest research advances in the extraction, purification, structural characterization, and bioactivities. It is intended to lay the theoretical and research foundations to enable further exploration and effective progress in the advancement towards the production of inulin. Graphical abstract

Background: The procedures of transcatheter tricuspid valve-in-valve (TTViV) replacement are challenging, and the clinical outcomes are still unclear. Our goal was to report the short- and mid-term clinical outcomes of patients who underwent a TTViV implantation guided by 3-dimensional (3D) printing. Methods: A retrospective analysis was performed on 6 patients who had TTViV implantation from May 2021 to March 2022. The median age was 51 years (range: 18-71 years), and 50.0% of the patients were male. Imaging assessments and 3D printing were performed on all 6 patients before the procedures. The perioperative data were evaluated, and the patients were followed up. Results: Among the 6 patients, the etiologies of conditions affecting the tricuspid valves at baseline varied widely, including 1 case of Ebstein anomaly, 2 cases of infective endocarditis, 1 case of ventricular septal defect, and 2 cases of rheumatic heart disease. TTViV implantation was successfully performed in all 6 patients via the femoral vein approach; postoperative tricuspid regurgitation disappeared immediately, and the hemodynamic results were satisfactory. During the follow-up, all patients had significant improvement in symptoms and functional status. Conclusions: TTViV implantation for the treatment of degenerated tricuspid bioprostheses should be considered safe and effective. Multimodal imaging and 3D printing may provide effective guidance for conducting the procedure. Clinical Trial Registration: ClinicalTrials.gov Protocol Registration System (NCT02917980). Résumé: Contexte: Les interventions de remplacement par cathéter de la valve tricuspide avec la technique dite « valve-in-valve » (TTViV) sont délicates, et les résultats cliniques sont encore peu clairs. Notre objectif était de rapporter les résultats cliniques à court et à moyen terme obtenus chez des patients ayant subi une implantation TTViV guidée par l’impression en trois dimensions (3D). Méthodologie: Une analyse rétrospective portant sur six patients ayant subi une implantation TTViV entre mai 2021 et mars 2022 a été réalisée. L’âge médian était de 51 ans (min.-max. : 18-71 ans), et 50,0 % des patients étaient des hommes. Des examens d’imagerie et des impressions 3D ont été effectués avant l’intervention pour chacun des six patients. Les données périopératoires ont été analysées, et les patients ont fait l’objet d’un suivi. Résultats: Les affections initiales touchant la valve tricuspide chez les six patients avaient des causes variables, soit un cas de maladie d’Ebstein, deux cas d’endocardite infectieuse, un cas de défaut de communication interventriculaire, et deux cas de cardiopathie rhumatismale. Une implantation TTViV a été réalisée chez les six patients, par cathétérisme fémoral. La régurgitation tricuspide postopératoire a disparu immédiatement et les résultats hémodynamiques étaient satisfaisants. Durant le suivi, tous les patients ont obtenu une amélioration significative de leurs symptômes et de leur état fonctionnel. Conclusions: L’implantation TTViV pour le traitement d’une bioprothèse tricuspide dégénérée devrait être considérée comme sûre et efficace. L’imagerie multimodale et l’impression 3D peuvent fournir des directives efficaces pour la réalisation de l’intervention. Enregistrement des essais cliniques: ClinicalTrials.gov Protocol Registration System (NCT02917980).

Abstract Background Social anxiety symptoms are common and harmful psychological illness in college students. Although some studies have illustrated that physical activity could reduce social anxiety symptoms, the specific mechanism is still unclear. Based on theoretical studies on resilience and sleep, this study constructed a serial mediation model to explore whether they mediate between physical activity and social anxiety symptoms among college students. Methods This study surveyed 9,530 college students from three colleges in China to explore the mediating effect of physical activity and sleep problems between physical activity and social anxiety symptoms. Participants were investigated with the International Physical Activity Questionnaire, Connor-Davidson Resilience Scale, Sleep-related problems, and the Social Interaction Anxiety Scale and the Social Phobia Scale. Correlations between variables were analysed using Pearson correlation analysis and mediation analyses were performed using SPSS PROCESS macro 3.3 software. Result The study found that physical activity was negatively associated with social anxiety symptoms and sleep problems, but positively with psychological resilience. After controlling for sociodemographic variables, physical activity can not only indirectly alleviate social anxiety symptoms through the separate mediation of psychological resilience and sleep problems, but also through the serial mediation of psychological resilience and sleep problems. Conclusion These results suggest that improving physical activity levels could reduce social anxiety scores by increasing psychological resilience and sleep quality. This is of great reference significance for the prevention and intervention of college students’ mental health.

Abstract Objective Diabetes is considered a significant risk factor for the development of atrial fibrillation/flutter (AF/AFL). However, there is still insufficient evidence to determine the varying effects of different hypoglycemic drugs (HDs) on the incidence of new-onset AF/AFL in diabetic patients. To address this gap, we conducted a network meta-analysis to investigate whether various HDs have different effects on the risk of new-onset AF/AFL compared with insulin. Method We conducted a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify all clinical trials investigating the association between various HDs or insulin and incident AF/AFL up until April 1, 2024. Bayesian random-effects model was used for network meta-analysis, and the results were expressed as relative risk (RR) and 95% confidence interval (CI). Result After searching 2070 articles, a total of 12 studies (2,349,683 patients) were included in the network meta-analysis. The treatment regimen comprised insulin and 8 HDs hypoglycemic drugs, which are sodium-dependent glucose transporters 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), metformin (Met), sulfonylureas (SU), non-sulfonylureas (nSU), thiazolidinedione (TZD) and α-glycosidase inhibitors (AGI). The use of SGLT2i [RR 0.23, 95%CI (0.11, 0.49)], GLP-1RA [RR 0.28, 95%CI (0.13, 0.57)], and DPP4i [RR 0.34, 95%CI (0.17, 0.67)] demonstrated significant efficacy in reducing the incidence of new-onset AF/AFL when compared to insulin. When HDs were compared in pairs, SGLT2i is more effective than Met [RR 0.35, 95% CI (0.19, 0.62)], SU (RR 0.27, 95% CI (0.14, 0.51)], nSU [RR 0.28, 95% CI (0.08, 0.95)], TZD [RR 0.34, 95% CI (0.17, 0.7)], GLP-1RA is more effective Met [RR 0.42, 95% CI (0.25, 0.71)], SU (RR 0.33, 95% CI (0.18, 0.6)], TZD [RR 0.41, 95% CI (0.21, 0.82)], while Met[RR 1.98, 95% CI (1.23, 3.23)], SU [RR 2.54, 95% CI (1.46, 4.43)], TZD [RR 2.01, 95% CI (1.05, 3.79)] was not as effective as DPP4i. Conclusion SGLT-2i, GLP-1RA, and DPP4i showed a superior efficacy in reducing the risk of new-onset AF/AFL compared to insulin therapy.

Study Region: The two field runoff experimental sites, Baitaqiao and Wangmuguan, are located in the plains of the Taihu Basin, China. Study Focus: This study investigates the hydrological cycle mechanisms in the Taihu Basin plains, aiming to support the development of next-generation, physically-based, refined hydrological models. Two experimental sites were established to comprehensively monitor hydrometeorological variables, including rainfall, evaporation, groundwater depth, soil water content, outlet flow, and other hydrological and meteorological factors. The study analyzes runoff processes and patterns under varying rainfall amounts and intensities, and examines the impacts of rainfall, groundwater depth, and micro-topography on runoff generation. Additionally, existing Taihu Basin models were used to simulate the rainfall-runoff process, with a focus on model errors and the significant role of rainfall-runoff patterns and micro-topography in the hydrological cycle. New Hydrological Insights for the Region: This study provides a comprehensive clarification of the parameters for the saturation-excess runoff model in humid agricultural plains, offering valuable references for the calibration of hydrological models in similar regions. While the saturation-excess runoff model predominates in the Taihu Basin, the research also identifies the occurrence of infiltration-excess and mixed runoff mechanisms under specific conditions, thus highlighting the limitations of relying solely on the saturation-excess runoff model. Furthermore, the study demonstrates the significant impacts of rainfall amount, rainfall intensity, groundwater depth, and microtopography on rainfall-runoff processes. Through a mechanistic analysis of these factors, the findings provide a theoretical foundation for the refinement of physically based, fine-scale hydrological cycle models, advancing the understanding of hydrological processes and supporting future model development in plain areas.

The 6G technology is expected to revolutionize wireless networks by enabling intelligent connectivity of all devices. The concept of a 6G green network aims for ubiquity, intelligence, simplicity, environmental friendliness, and carbon reduction. This paper delves into the essential energy-saving technologies for 6G radio access networks within an energy-efficient framework and proposes a multi-tiered cloud-enabled endogenous intelligent architecture for 6G wireless networks. It provides a design case for an intelligent endogenous wireless network architecture in the context of 6G. Building upon this intelligent network architecture, the paper introduces novel ideas for protocol stack design and multi-rate signaling transmission semantic transmission model. Furthermore, it analyzes the relationship between AI model deployment and energy efficiency while presenting an example of hierarchical deployment of federated learning models. The paper suggests deploying a hierarchical federated learning model within the network architecture to enhance energy efficiency.

Understanding the patterns and drivers of plant functional diversity is crucial for assessing the functioning and resilience of terrestrial ecosystems to global climate change. Despite the well-documented variability in plant species richness with elevation, the elevational patterns and underlying mechanisms of functional diversity remain poorly understood. This study employed drone equipped with multispectral and light detection and ranging (LiDAR) sensors to investigate the elevational gradients (3208 m to 3984 m) of physiological and morphological functional diversity of canopy tree species in six 1-hectare plots in Baima Snow Mountain, Yunnan, China. Results demonstrated that drone-based multispectral and LiDAR data enabled high-resolution mapping of physiological and morphological functional diversity in forest canopies over large areas. Importantly, functional diversity declined with increasing elevation, with a more pronounced pattern observed for physiological traits compared to morphological traits. Variance partitioning analysis revealed that functional richness was primarily driven by climatic and edaphic factors, particularly temperature, while plant factors played a subordinate role, interacting with climate and soil. Our findings highlight the potential of drone for rapid, large-scale monitoring and mapping of canopy species functional diversity in forests. Moreover, the influences of climate and soil factors on functional diversity suggest that future global warming may enhance functional diversity in alpine forest ecosystems, with implications for ecosystem functioning and services.

Background Inflammation and metabolic disturbances are key culprits in the pathogenesis of obesity‐associated cardiomyopathy. The NLRP3 (nucleotide‐binding oligomerization domain‐like receptor 3) inflammasome mediates the release of the proinflammatory cytokines IL‐1β (interleukin‐1β) and IL‐18 by activating caspase‐1, which is strongly implicated in metabolic disturbances. We here sought to determine whether NLRP3 inflammasome inhibition could ameliorate obesity cardiomyopathy and if so, to further explore its underlying mechanisms. Methods and Results Male mice were fed a high‐fat diet for 24 weeks to induce obesity cardiomyopathy. MCC950 was used to inhibit NLRP3 inflammasome activation. Recombinant adeno‐associated virus serotype 9 encoding TXNIP (thioredoxin‐interacting protein) under cTnT (cardiac troponin T) promoter and the mitochondrial‐targeted antioxidant MitoTEMPO were injected into obese mice to investigate the specific mechanism. To mimic obesity cardiomyopathy in vitro, neonatal rat ventricular myocytes transfected with the small interfering RNA against TXNIP were incubated with 400 μmol palmitic acid for 24 hours. NLRP3 inflammasome was significantly increased in obese hearts. NLRP3 inflammasome inhibition by NLRP3 deletion or MCC950 prevented obesity‐induced cardiac systolic and diastolic dysfunction, myocardial hypertrophy and fibrosis, and excessive lipid accumulation in male mice. Conversely, TXNIP overexpression worsened obesity‐associated cardiomyopathy. Similarly, MCC950 treatment or TXNIP knockdown reduced palmitic acid‐induced NLRP3 inflammasome activation and lipid storage. Mechanistically, abnormal NF‐κB (nuclear factor kappa B) pathway activation, increased mitochondrial reactive oxygen species, and elevated TXNIP levels led to excessive NLRP3 inflammasome activation. Conclusions Our study confirms that aberrant NLRP3 inflammasome activation in cardiomyocytes worsens obesity‐associated cardiomyopathy and implicates inhibition of NLRP3 inflammasome as a potent therapeutic approach for obesity cardiomyopathy.

Copper (Cu) is recognized as an essential trace elements for the body; However, excessive levels of Cu can lead to toxic effects. We investigated the effects of Cu2+(75 μg/L, 150 μg/L, and 300 μg/L) on the rainbow trout liver. Combination of transcriptome and metabolome analyses, the regulatory mechanisms of the liver under Cu stress were elucidated. The results showed that Cu affected the antioxidant levels, leading to disruptions in the normal tissue structure of the liver. Combined transcriptome and metabolome analyses revealed significant enrichment of the insulin signaling pathway and the adipocytokine signaling pathway. Additionally, Cu2+ stress altered the amino acid metabolism in rainbow trout by reducing serine and arginine levels while increasing proline content. Apoptosis is inhibited and autophagy and lipid metabolism are suppressed; In summary, Cu2+ stress affects energy and lipid metabolism, and the reduction of serine and arginine represents a decrease in the antioxidant capacity, whereas the increase in proline and the promotion of apoptosis potentially serving as crucial strategies for Cu2+ resistance in rainbow trout. These findings provided insights into the regulatory mechanisms of rainbow trout under Cu2+ stress and informed the prevention of heavy metal pollution and the selection of biomarkers under Cu pollution.

ObjectivesTo evaluate the changes in distal vascular morphology and hemodynamics in patients with extremely severe aortic coarctation (CoA) after covered palliative (CP) stent dilation with different surgical strategies.Materials and methodsPerioperative computed tomography angiography and digital subtraction angiography were utilized to construct three aortic models with varying stenosis rates and one follow-up model in a patient with extremely severe CoA. The models included: an idealized non-stenosed model (A: 0%), a model post initial stent deployment (B: 28%), a model post balloon expansion (C: 39%), and a model 18 months after post-balloon expansion (D: 39%). Consistent boundary conditions were applied to all models, and hemodynamic simulation was conducted using the pure fluid method.ResultsThe narrowest and distal diameter of the stent increased by 34.71% and 59.29%, respectively, from model B to C. Additionally, the distal diameter of the stent increased by −13.80% and +43.68% compared to the descending aorta diameter, respectively. Furthermore, the ellipticity of the maximum cross-section of the aneurysm region in model A to D continued to increase. The oscillatory shear index at the stenosis to the region of the aneurysm were found to be higher in Models A and B, and lower in Models C and D. At the moment of maximum flow velocity, the blood flow distribution in models A and B was more uniform in the widest section of the blood vessels at the distal end of the stenosis, whereas models C and D exhibited disturbed blood flow with more than 2 eddy currents. The time-averaged wall shear stress (TAWSS) decreased in the distal and basal aneurysms, while it significantly increased at the step position. The aneurysmal region exhibited an endothelial cell activation potential value lower than 0.4 Pa−1.ConclusionIn patients with extremely severe CoA, it is crucial to ensure that the expanded diameter at both ends of the CP stent does not exceed the native vascular diameter during deployment. Our simulation results demonstrate that overdilation leads to a decrease in the TAWSS above the injured vessel, creating an abnormal hemodynamic environment that may contribute to the development and enlargement of false aneurysms in the early postoperative period. Clinical Trial RegistrationClinicalTrials.gov, (NCT02917980).

With the maturity of 5G technology and global commercialization, scholars in institutions and industrial circles began to research 6G technology. An important innovation of 6G technology is to integrate artificial intelligence (AI) technology and communication technology to build a highly endogenous intelligent communication network. This paper investigates the process of AI technology introduced into the field of communication and reviews the use cases of the simulation and application of AI algorithms being discussed in 3GPP meetings in industry circles. In this research report, we first investigate the progress of AI technology in 5G network architecture and then discuss the requirements of endogenous intelligent 6G networks, which leads to the possible network architecture. This work aims to provide enlightening guidance for subsequent research of intelligence-endogenous 6G network.

Abstract Background Specific pathogen-free ducks are a valuable laboratory resource for waterfowl disease research and poultry vaccine development. High throughput sequencing allows the systematic identification of structural variants in genomes. Copy number variation (CNV) can explain the variation of important duck genetic traits. Herein, the genome-wide CNVs of the three experimental duck species in China (Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)) were characterized using resequencing to determine their genetic characteristics and selection signatures. Results We obtained 4,810 CNV regions (CNVRs) by merging 73,012 CNVs, covering 4.2% of the duck genome. Functional analysis revealed that the shared CNVR-harbored genes were significantly enriched for 31 gene ontology terms and 16 Kyoto Encyclopedia of Genes and Genomes pathways (e.g., olfactory transduction and immune system). Based on the genome-wide fixation index for each CNVR, growth (SPAG17 and PTH1R), disease resistance (CATHL3 and DMBT1), and thermoregulation (TRPC4 and SLIT3) candidate genes were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Conclusions In conclusion, we investigated the genome-wide distribution of experimental duck CNVs, providing a reference to establish the genetic basis of different phenotypic traits, thus contributing to the management of experimental animal genetic resources.

Abstract Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. Methods A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. Results Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. Conclusion This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells. Graphical Abstract

Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer’s disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.

The independent innovation of agricultural enterprises ensures national food security through enhancing food production efficiency and optimizing food nutritional quality. Independent innovation is an important way for the sustainable growth of agricultural enterprises. However, in this process, there are issues such as long cycles and high risks. Based on this, using the panel data of China’s listed agricultural enterprises from 2007 to 2021, this study empirically examined the impact of independent innovation on the sustainable growth of agricultural enterprises, as well as the moderating effects of internal drivers (digital transformation) and external pull factors (government subsidies) through a two-way fixed effects model. The findings are the following: (1) The impact of independent innovation on the sustainable growth of agricultural enterprises exhibits an “inverted U-pattern”. When the R&D investment of agricultural enterprises accounts for 77.85% of operating income, the sustainable growth ability of agricultural enterprises is the highest. (2) Compared with large agricultural enterprises, small and medium-sized agricultural enterprises reach the threshold of independent innovation ability later, and the incentive effect range of independent innovation is longer. (3) Independent innovation exerts a more significant “inverted U” effect on the sustainable growth of non-state-owned agricultural enterprises and agricultural enterprises in the mature stage, while its impact on the sustainable growth of state-owned agricultural enterprises and agricultural enterprises in the growth and decline stages is not significant. (4) Government subsidies can help enhance the positive impact of independent innovation on the sustainable growth of agricultural enterprises when it does not exceed the threshold but cannot alleviate the negative impact of independent innovation on the sustainable growth of agricultural enterprises when it exceeds the threshold; investment in digital transformation not only helps to enhance the positive impact of independent innovation on the sustainable growth of agricultural enterprises when it does not exceed the threshold but also helps to alleviate the negative impact of independent innovation on the sustainable growth of agricultural enterprises when it exceeds the threshold. The research results provide data support for agricultural enterprises to carry out innovation activities under internal drive and external pull. At the same time, it is of great significance for the national implementation of the strategy of storing food in technology and food security strategy.

Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.

ObjectiveThe progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT.MethodPubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated.ResultAfter screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo.ConclusionLong-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.

Abstract The development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS2) core coated with Manganese dioxide (MnO2), which possessed a good photothermal effect and could produce Fenton-like Mn2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH2) to improve their biocompatibility, resulting in the formation of MoS2@MnO2-PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS2@MnO2-PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.

This study addresses the issue of unsatisfactory smoothness in the movement of integrated internal and external cross roller bearings post-assembly, which compromises the movement flexibility of the finished bearing and fails to meet index requirements. Focusing on a specific type of precision cross roller bearing, this paper establishes a finite element explicit dynamic simulation model that takes into account the plugging position and matching relationship. A transient dynamic simulation of the roller blockage process was conducted, yielding insights into the contact pressure and deformation experienced by the roller and plug during this blockage. The results indicate that when both the taper pin are positioned centrally, and the plug matching clearance, plug sag and protruding amount, and plug rotation offset degrees are all set to 0 μm, the contact pressure between the roller and raceway, as well as the roller deformation displacement, are minimized. The plugging position and fit were subsequently validated through testing, which also measured the impact of these parameters on the roundness of the raceway surface and the bearing’s friction torque. The test findings corroborate that when the taper and pin are centrally aligned, and the stopper clearance is 5 μm, with the plug sag, protrusion, and offset all at 0 μm, the roundness of the raceway surface and the bearing’s friction torque reach their lowest values, thereby optimizing the stability of bearing motion. By comparing the simulation and experimental results, it is concluded that during bearing assembly, it is crucial to maintain the taper pin in a central position, control the plug matching clearance to approximately 5 μm, and ensure the plug sag, protrusion, and rotation offset amount are both at 0 μm. This approach guarantees optimal contact conditions and motion stability during operation. The findings of this research offer valuable design guidance for the selection of appropriate plugging positions and fits in precision cross roller bearings.

Seed enterprises are crucial for ensuring national food security, the driving force behind the seed industry’s advancement, and the core entity in constructing a modern seed industry system. At the micro and macro levels, agricultural seed enterprises face challenges and pressures in earning excess profits, enhancing their competitive edge, and resisting the incursion of multinational seed enterprises. This article selects panel data from 49 listed seed enterprises in China from 2015 to 2022 and uses methods such as global principal component analysis (GPCA) and Q-type cluster analysis to measure and evaluate the competitiveness of Chinese seed enterprises. Research has found that: (1) From 2015 to 2022, the overall competitiveness of listed Chinese agricultural seed enterprises has shown an upward trend. The competitiveness of agricultural seed enterprises can be further decomposed into operational capabilities, growth capabilities, production efficiency, technological innovation capabilities, etc. (2) The top ten agricultural seed enterprises in China have obvious advantages in operational and technological innovation capabilities, but their growth capabilities and production efficiency are insufficient. (3) Regarding the vertical comparison of the seed industry, the ranking of the competitiveness of Chinese listed agricultural seed enterprises from strong to weak is wheat seed enterprises > other seed enterprises > melon and vegetable seed enterprises > corn seed enterprises > rice seed enterprises. (4) Compared with international seed industry giants, there are various reasons why China’s top agricultural seed enterprises have weaker competitiveness, specifically reflected in research and development investment, scale and market share, industrial layout, and other aspects. The findings of this research offer empirical evidence to bolster the competitiveness of seed enterprises and advance the seed industry, while also aiding in fortifying the nation’s strategic oversight of the seed sector, bearing profound implications for safeguarding food security.

ObjectiveIt is advised that patients engage in physical activity to enhance their quality of life and achieve better results. The purpose of the current study was to measure the efficacy of exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with AF.MethodA comprehensive systematic literature search was performed in PubMed, Embase, and Web of Science from 1991 to 2023 for RCTs comparing physical exercise combined with AF routine treatments to routine treatments alone. The meta-analysis was conducted following PRISMA guidelines. Our main outcomes were physical ability (measured by the 6-min walk test, 6MWT), cardiac function (measured by left ventricular ejection fraction, LVEF) and cardiopulmonary fitness (measured by peak oxygen uptake and resting heart rate). Quality assessments were conducted using the Cochrane Collaboration tool.ResultsThirteen trials involving 672 patients met the criteria for analysis. The results showed that physical exercise increased physical ability by improving the 6MWT (m) performance (MD = 96.99, 95% CI: 25.55–168.43; Z = 2.66; p = 0.008); and enhanced peak VO2 (ml/kg per min) (MD = 4.85, 95% CI: 1.55–8.14; Z = 2.89; p = 0.004) while reducing resting heart rate (beats per minute, bpm) (MD = −6.14, 95% CI: −11.30 to −0.98; Z = 2.33; p = 0.02). However, the results showed that regular exercise could improve LVEF (%) inpatients clinically, which had no statistic difference between experimental and control group (MD = 1.49, 95% CI: −0.25–3.24; Z = 1.68; p = 0.09).ConclusionOur meta-analysis shows that physical exercise is an effective intervention to improve the exercise ability and cardiopulmonary fitness for AF patients. Meanwhile, we also do not exclude the positive effect of exercise on the improvement of cardiac function (LVEF) in patients with AF. To this end, doctors should consider the positive impact of exercise on patients and give advice on exercise limits in practical clinical practice.

Conclusions: These results elucidate the roles of ferroptosis, autophagy, and their interactions in the pathogenesis of diabetic liver injury, offering potential therapeutic targets. Furthermore, they shed light on the pathogenesis of ferroptosis and other diabetic complications.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Despite remarkable advances in understanding the mechanisms underlying inflammation, the currently available anti‐inflammatory therapies have many limitations, such as poor efficacies, low selectivity, and severe adverse effects. Bioactive materials with intrinsically anti‐inflammatory activities have emerged as promising drug candidates for the treatment of inflammatory disorders. Among them, nanotherapies based on bioactive cyclodextrin (CD) materials have attracted much attention, owing to their multiple advantages, including broad availability, well‐controlled structures, easy functionalization, good processibility, high cost‐effectiveness, and excellent biocompatibility. This review provides a comprehensive overview of the recent advancements in the development and applications of anti‐inflammatory nanoparticles (NPs) based on bioactive CD materials, with special focus on reactive oxygen species‐scavenging NPs and NPs capable of regulating inflammatory cell recruitment and activation. In addition, the applications of these anti‐inflammatory nanotherapies in the treatment of different acute/chronic inflammatory diseases are highlighted. Furthermore, major challenges in the clinical translation of these new generation anti‐inflammatory therapies derived from bioactive CD materials are discussed.

Neurons can be abstractly represented as skeletons due to the filament nature of neurites. With the rapid development of imaging and image analysis techniques, an increasing amount of neuron skeleton data is being produced. In some scientific studies, it is necessary to dissect the axons and dendrites, which is typically done manually and is both tedious and time-consuming. To automate this process, we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning (GDL). We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains, and the results are promising for its application in neuroscience studies.

Abstract Luminescence nanoprobes have been extensively investigated for many biomedical applications, ranging from cell/tissue imaging, real‐time monitoring pathophysiological changes, drug discovery, bioassays, image‐guided surgery, and therapeutic evaluations, mainly due to their excellent physicochemical properties such as tailorable size, controlled morphology, and regulatable luminescence performances. In particular, rationally designed luminescence nanoprobes with reasonable functional integration enable pharmacological effect‐based drug screening, quantification of biological/pharmaceutical agents, and monitoring therapeutic responses of different drugs. This review provides an overview of the applications of different types of luminescence nanoprobes in drug discovery and development, involving various nanoprobes for high‐throughput and high‐content drug screening, pharmaceutical analysis, and therapeutic evaluations in cancers, cardiovascular diseases, and other typical inflammatory diseases. Moreover, challenges and future perspectives regarding future applications of luminescence nanoprobes in the drug discovery field are also discussed.

Powdery mildew significantly impacts the yield of natural rubber by being one of the predominant diseases that affect rubber trees. Accurate, non-destructive recognition of powdery mildew in the early stage is essential for the cultivation management of rubber trees. The objective of this study is to establish a technique for the early detection of powdery mildew in rubber trees by combining spectral and physicochemical parameter features. At three field experiment sites and in the laboratory, a spectroradiometer and a hand-held optical leaf-clip meter were utilized, respectively, to measure the hyperspectral reflectance data (350–2500 nm) and physicochemical parameter data of both healthy and early-stage powdery-mildew-infected leaves. Initially, vegetation indices were extracted from hyperspectral reflectance data, and wavelet energy coefficients were obtained through continuous wavelet transform (CWT). Subsequently, significant vegetation indices (VIs) were selected using the ReliefF algorithm, and the optimal wavelengths (OWs) were chosen via competitive adaptive reweighted sampling. Principal component analysis was used for the dimensionality reduction of significant wavelet energy coefficients, resulting in wavelet features (WFs). To evaluate the detection capability of the aforementioned features, the three spectral features extracted above, along with their combinations with physicochemical parameter features (PFs) (VIs + PFs, OWs + PFs, WFs + PFs), were used to construct six classes of features. In turn, these features were input into support vector machine (SVM), random forest (RF), and logistic regression (LR), respectively, to build early detection models for powdery mildew in rubber trees. The results revealed that models based on WFs perform well, markedly outperforming those constructed using VIs and OWs as inputs. Moreover, models incorporating combined features surpass those relying on single features, with an overall accuracy (OA) improvement of over 1.9% and an increase in F1-Score of over 0.012. The model that combines WFs and PFs shows superior performance over all the other models, achieving OAs of 94.3%, 90.6%, and 93.4%, and F1-Scores of 0.952, 0.917, and 0.941 on SVM, RF, and LR, respectively. Compared to using WFs alone, the OAs improved by 1.9%, 2.8%, and 1.9%, and the F1-Scores increased by 0.017, 0.017, and 0.016, respectively. This study showcases the viability of early detection of powdery mildew in rubber trees.

The Qinghai-Tibetan Plateau (QTP) has nurtured a rich diversity of species because of its unique geographical and environmental conditions. Gymnocypris species (subfamily Schizopygopsinae) are primitive fishes that live in the special environment of the plateau, and their evolution and distribution are inseparable from the historical changes of the QTP. Recently, the resources of Gymnocypris species have been decreasing due to habit deterioration and the intensification of human activities. Therefore, the scientific conservation of the genetic resources of Gymnocypris species is urgently required. In this study, we established two models for the priority conservation assessment of germplasm resources of Gymnocypris species on the basis of the genetic diversity and phylogenetic relationships of 674 individuals from eight Gymnocypris species populations. The results show that the Gymnocypris potanini (GPO), Gymnocypris eckloni (GE), and Gymnocypris przewalskii (GPR) populations are the most genetically diverse in terms of combined genetic diversity values and should be prioritized for conservation. In terms of genetic contribution, the GPO, GE, and GPR populations have a positive impact on maintaining the distinctiveness and diversity of the entire Gymnocypris species population and should be prioritized for conservation. However, in terms of different evolutionary clades, the Gymnocypris namensis, Gymnocypris waddellii, Gymnocypris dobula, and GE populations in clade A should be given priority for protection, the GE population in clade B should be given priority, and the GPR population in clade C should be given priority. In conclusion, the two models and assessment of conservation priorities will provide a scientific basis for the conservation of Gymnocypris species.

Introduction Coronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors.Methods and analysis This protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030.Ethics and dissemination This study is a systematic review of published literature data and no special ethical approval was required.PROSPERO registration number CRD42022346189.

A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C60 molecule inside of the cavity and significantly improve the water-solubility of the C60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C60 and verifies the important role of C60 in preventing oxidative stress-related cardiovascular disease injury.

ABSTRACT: Specific pathogen-free ducks are important high-grade laboratory animals, with a key role in research related to poultry biosecurity, production, and breeding. However, the genetic characteristics of experimental duck varieties remain poorly explored. Herein we performed whole-genome resequencing to construct a single nucleotide polymorphism genetic map of the genomes of 3 experimental duck varieties [Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)] to determine their genetic characteristics and identify selection signatures. Subsequent analyses of population structure and genetic diversity revealed that each duck variety formed a monophyletic group, with SM showing richer genetic diversity than JD and SX. Further, on exploring shared selection signatures, we found 2 overlapping genomic regions on chromosome Z of all experimental ducks, which comprised immune response-related genes (IL7R and IL6ST). Moreover, growth and skeletal development (IGF1R and GDF5), meat quality (FoxO1), and stress resistance (HSP90B1 and Gpx8-b) candidate gene loci were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Our results identified the population genetic basis of experimental ducks at the whole-genome level, providing a framework for future molecular investigations of genetic variations and phenotypic changes. We believe that such studies will eventually contribute to the management of experimental animal resources.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology. Brain imaging biomarker genomics has been developed in recent years to reveal potential AD pathological mechanisms and provide early diagnoses. This technique integrates multimodal imaging phenotypes with genetic data in a noninvasive and high-throughput manner. In this review, we summarize the basic analytical framework of brain imaging biomarker genomics and elucidate two main implementation scenarios of this technique in AD studies: (1) exploring novel biomarkers and seeking mutual interpretability and (2) providing a diagnosis and prognosis for AD with combined use of machine learning methods and brain imaging biomarker genomics. Importantly, we highlight the necessity of brain imaging biomarker genomics, discuss the strengths and limitations of current methods, and propose directions for development of this research field.

The purpose of this study was to determine the efficacy of tannic acid on the antioxidative function, immunity, and intestinal barrier of broilers co-infected with coccidia and Clostridium perfringens (CCP). A total of 294 1-day-old arbor acres(AA) broilers were divided into three groups: control group (CON), CCP co-infected group (CCP), and 1000 mg/kg TA + CCP co-infected group (CTA). This trial lasted for 28 days. The results showed that the CCP group decreased the activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) levels and increased the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in the jejunum (p < 0.05). The mRNA levels of GSH-Px3 and CAT in the liver and jejunum, and the mRNA levels of GSH-Px3, SOD, HO-1, and NAD(P)H quinone oxidoreductase I (NQO1) in the liver were down-regulated by CCP challenge (p < 0.05). In addition, the Keap1 and Nrf2 mRNA levels in the liver and jejunum, jejunal glutathione S-transferase (GST), and heme-oxygenase-1 (HO-1) were upregulated in the CCP group compared with CON (p < 0.05). The mRNA levels of interleukin 8 (IL-8), IL-1β, inducible nitric oxide synthase (iNOS), and interferon γ (IFN-γ) in the jejunum were elevated, and jejunal mRNA levels of IL-10, zonula occludens protein1 (ZO-1), claudin-1, claudin-2, and occludin were decreased in the CCP treatment (p < 0.05). Dietary supplementation with 1000 mg/kg TA increased the activity of GSH-Px, T-SOD, CAT, and T-AOC and decreased the contents of H2O2 and MDA in the jejunum (p < 0.05). Compared with the CCP group, TA decreased the mRNA level of Keap1 and Nrf2 in the liver and jejunum, increased the GSH-Px3, SOD, and CAT mRNA in the liver, and alleviated the rise of IL-8, IL-1β, iNOS, and IFN-γ and decrease in IL-10, occludin gene expression in the jejunum (p < 0.05). In conclusion, the addition of 1000 mg/kg TA to the diet improved the jejunal barrier, mitigated the jejunal inflammation, and increased the antioxidant capacity of the liver and jejunum through the activation of the transcription factor Nrf2 downstream of the Nrf2-Keap1 pathway in broilers with NE condition.

This paper proposes a wireless network traffic prediction model based on long-term and short-term memory cyclic neural networks. Through simulation experiments, the throughput prediction of 5G wireless networks using different scheduling algorithms for many different types of services is studied. The results verify that the long short-term memory prediction model has acceptable prediction accuracy and algorithm training speed, meets the needs of wireless network traffic prediction, and has a good application prospect.

Abstract Background Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported. Methods We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer with the TCGA and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase were detected by qRT-PCR or western blotting in LNCaP and 22RV1 cells treated with DHT, R1881, or Enzalutamide. The effects of FOXO3a on catalase expression were tested by over-expressing or knocking down FOXO3a in LNCaP cells. Furthermore, the catalase activity and ROS level were detected in LNCaP cells treated with DHT. Cell proliferation and ROS were also analyzed in LNCaP which was treated with antioxidant. Results Results showed that the catalase expression was down-regulated in prostate cancer. A positive correlation between FOXO3a and catalase existed. DHT treatment could significantly reduce FOXO3a and catalase expression at mRNA and protein level in LNCaP cells. Catalase expression partly depended on FOXO3a as over-expression and knockdown of FOXO3a could result in the expresssion change of catalase. DHT treatment was found to inhibit catalase activity and increase ROS level in prostate cancer cell. Our study also demonstrated that antioxidant treatment reduced DHT-induced proliferation and ROS production in prostate cancer cell. Conclusions We discovered a novel mechanism by which DHT promotes prostate cancer cell proliferation via suppressing catalase activity and activating ROS signaling via a FOXO3a dependent manner.

【Objective】The study was performed to explore the germination characteristics of Passiflora edulia Sims seeds in order to lay a foundation for seed seedling raising and seed germination and character observation of hybrid offspring of P. edulia.【Method】P. edulia seeds were used as experimental materials to study the effects of different water temperatures (25, 45, 65, 85, 100 ℃), time of soaking in concentrated sulfuric acid (0, 0.5, 1, 2, 5, 8, 10 and 15 min), gibberellin concentrations (0, 200, 400 and 800 mg/L), culture temperatures (18, 28, 35, 18-28, 28-35 ℃), seed shells and different physical treatment methods (acupuncture and sanding) on seed germination of P. edulia. Taking germination rate, germination potential and germination index as test indexes, different germination conditions were evaluated to determine the suitable ones for seed germination.【Result】The germination rate of P. edulia seeds soaked in 65℃ warm water for 24 h was the highest (57.78%). The optimum soaking time in concentrated sulfuric acid was 8 min, the germination rate, germination potential and germination index were 77.38%, 77.38% and 3.39%, respectively. The germination rate was 81.11% when the soaking concentration of gibberellin was 400 mg/L. The optimum culture temperature for germination was 28-35℃, and the germination rate was 64.44%. The seed germination rate of P. edulia was 76.67%. There was no significant difference in seed germination between physical treatment and acupuncture treatment, but acupuncture was not well controlled and easy to hurt seed embryo. Grinding treatment was the best, and the germination rate was 60%.【Conclusion】The seeds of P. edulia are suitable to be soaked in 65℃ warm water for 24 h or soaked in concentrated sulfuric acid for 8 min for 24 h; The seed germination rate can be effectively improved by grinding treatment or soaking in 400 mg/L gibberellin for 24 h. The suitable germination culture temperature is 28-35℃.

BackgroundLead-induced tricuspid regurgitation is one of the complications after permanent pacemaker implantation (PPI) and refers to tricuspid regurgitation (TR) caused by the lead in the right ventricle (RV).ObjectivesTo study the clinical characteristics of severe TR after PPI and the effect of transcatheter tricuspid valve replacement (TTVR) with the guidance of 3-dimensional (3D) printing.MethodsThis study was a single-center, descriptive study. Six patients with severe TR after PPI were enrolled in Xijing Hospital from January 2020 to May 2020. Before TTVR, the 3D printed tricuspid valve (TV) model was used for evaluation in the bench test. LuX-Valve was implanted under the guidance of TEE and x-ray fluoroscopy, and all patients underwent transatrial access. Six patients’ data were collected at baseline, before discharge, and 6 months, 1 year and 2 years after TTVR.ResultsThe LuX-Valve was successfully implanted in 6 patients, TR was significantly reduced to ≤2+, and no deaths or cardiopulmonary bypass occurred during procedures. Three cases were caused by TV expansion: Patient #4 had TR caused by lead adhesion to TV, Patient #2 had TR caused by lead winding, and Patient #6 had TR caused by lead impingement on TV. During the 2-year follow-up, TTE revealed that 5 patients had no/trace regurgitation, and one patient (Patient #5) had mild regurgitation. All 6 patients (100.0%) reached primary endpoints.ConclusionTTVR guided by 3D printing is safe and effective in the treatment of severe TR associated with permanent pacemaker lead, providing prospects and possibilities for the precise treatment of TV-related diseases.Clinical Trial Registration: ClinicalTrials.gov Protocol Registration System (NCT02917980).