Search

Abstract Background Camptothecin (CPT) is one of the frequently used small chemotherapy drugs for treating hepatocellular carcinoma (HCC), but its clinical application is limited due to severe toxicities and acquired resistance. Combined chemo-gene therapy has been reported to be an effective strategy for counteracting drug resistance while sensitizing cancer cells to cytotoxic agents. Thus, we hypothesized that combining CPT with miR-145 could synergistically suppress tumor proliferation and enhance anti-tumor activity. Methods Lactobionic acid (LA) modified lipid nanoparticles (LNPs) were developed to co-deliver CPT and miR-145 into asialoglycoprotein receptors-expressing HCC in vitro and in vivo. We evaluated the synergetic antitumor effect of miR-145 and CPT using CCK8, Western blotting, apoptosis and wound scratch assay in vitro, and the mechanisms underlying the synergetic antitumor effects were further investigated. Tumor inhibitory efficacy, safety evaluation and MRI-visible ability were assessed using diethylnitrosamine (DEN) + CCl4-induced HCC mouse model. Results The LA modification improved the targeting delivery of cargos to HCC cells and tissues. The LA-CMGL-mediated co-delivery of miR-145 and CPT is more effective on tumor inhibitory than LA-CPT-L or LA-miR-145-L treatment alone, both in vitro and in vivo, with almost no side effects during the treatment period. Mechanistically, miR-145 likely induces apoptosis by targeting SUMO-specific peptidase 1 (SENP1)-mediated hexokinase (HK2) SUMOylation and glycolysis pathways and, in turn, sensitizing the cancer cells to CPT. In vitro and in vivo tests confirmed that the loaded Gd-DOTA served as an effective T1-weighted contrast agent for noninvasive tumor detection as well as real-time monitoring of drug delivery and biodistribution. Conclusions The LA-CMGL-mediated co-delivery of miR-145 and CPT displays a synergistic therapy against HCC. The novel MRI-visible, actively targeted chemo-gene co-delivery system for HCC therapy provides a scientific basis and a useful idea for the development of HCC treatment strategies in the future.

Abstract Efficient intracellular delivery is crucial for biotherapeutics, such as proteins, oligonucleotides, and CRISPR/Cas9 gene-editing systems, to achieve their efficacy. Despite the great efforts of developing new intracellular delivery carriers, the lack of straightforward methods for intracellular delivery quantification limits further development in this area. Herein, we designed a simple and versatile bioorthogonal luminescent reaction (BioLure assay) to analyze intracellular delivery. Our results suggest that BioLure can be used to estimate the amount of intracellularly delivered molecules after electroporation, and the estimation by BioLure is in good correlation with the results from complementary methods. Furthermore, we used BioLure assay to correlate the intracellularly-delivered RNase A amount with its tumoricidal activity. Overall, BioLure is a versatile tool for understanding the intracellular delivery process on live cells, and establishing the link between the cytosolic concentration of intracellularly-delivered biotherapeutics and their therapeutic efficacy.

Abstract Cations such as K+ play a key part in the CO2 electroreduction reaction, but their role in the reaction mechanism is still in debate. Here, we use a highly symmetric Ni-N4 structure to selectively probe the mechanistic influence of K+ and identify its interaction with chemisorbed CO2 −. Our electrochemical kinetics study finds a shift in the rate-determining step in the presence of K+. Spectral evidence of chemisorbed CO2 − from in-situ X-ray absorption spectroscopy and in-situ Raman spectroscopy pinpoints the origin of this rate-determining step shift. Grand canonical potential kinetics simulations - consistent with experimental results - further complement these findings. We thereby identify a long proposed non-covalent interaction between K+ and chemisorbed CO2 −. This interaction stabilizes chemisorbed CO2 − and thus switches the rate-determining step from concerted proton electron transfer to independent proton transfer. Consequently, this rate-determining step shift lowers the reaction barrier by eliminating the contribution of the electron transfer step. This K+-determined reaction pathway enables a lower energy barrier for CO2 electroreduction reaction than the competing hydrogen evolution reaction, leading to an exclusive selectivity for CO2 electroreduction reaction.

Abstract Mine flooding accidents have occurred frequently in recent years, and the predicting of mine water inflow is one of the most crucial flood warning indicators. Further, the mine water inflow is characterized by non-linearity and instability, making it difficult to predict. Accordingly, we propose a time series prediction model based on the fusion of the Transformer algorithm, which relies on self-attention, and the LSTM algorithm, which captures long-term dependencies. In this paper, Baotailong mine water inflow in Heilongjiang Province is used as sample data, and the sample data is divided into different ratios of the training set and test set in order to obtain optimal prediction results. In this study, we demonstrate that the LSTM-Transformer model exhibits the highest training accuracy when the ratio is 7:3. To improve the efficiency of search, the combination of random search and Bayesian optimization is used to determine the network model parameters and regularization parameters. Finally, in order to verify the accuracy of the LSTM-Transformer model, the LSTM-Transformer model is compared with LSTM, CNN, Transformer and CNN–LSTM models. The results prove that LSTM-Transformer has the highest prediction accuracy, and all the indicators of its model are well improved.

Abstract Autophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.

Abstract Earthquake cycle simulations based on the rate-and-state friction formulation are evolutions of nonlinear dynamical systems (NDS). The term “cycle” implies an overall stable structure that is a phase-space attractor naturally traced out by trajectories of NDS as it evolves. Quantitatively characterizing these attractors should be a basis for measuring complexities of the simulated earthquake cycles, i.e. to determine if and how regular or chaotic they are. I first revisit the textbook-standard quasi-dynamic spring-slider system from an NDS perspective, explicitly showing the attractors, their relationship with the parameters of the NDS, and how they can be characterized taken advantage of their low-dimensionality while aiming to extend the analysis to high-dimensionality. I evaluate two approaches, computing the Lyapunov exponents (LEs) and measuring correlation dimensions, with the simple spring-slider and earthquake-cycle examples whose phase-space attractors can be visually verified. I conclude LEs are too inconvenient and computationally expensive to use whereas measuring correlation dimensions is an easy and effective approach even with highly non-uniform time sampling present in all simulations. For earthquake-cycle simulations, an attractor reconstruction is performed based on Taken’s theorem to corroborate my correlation-dimension results. The current method is limited in its ability to detect chaos in a dichotomous manner, which illuminates the direction for future study. An improving ability to quantitatively characterize earthquake-cycle simulations as an overall stable structure offers new opportunities to understand exotic seismic observations such as slow-slip events and enables more informative comparison with real data, particularly from paleoseismology, which could have far-reaching implications in earthquake forecasting.

Abstract Propagation models are essential for the prediction of received signal strength and the planning of wireless systems in a given environment. The vector parabolic equation (VPE) method has been widely applied to the modelling of radio wave propagation in tunnels. However, carrying out simulations for large‐scale environments is still computationally expensive. A convolutional neural network (CNN)‐based propagation model, which can provide high‐fidelity received signal strength prediction based on results from low‐cost VPE simulations, is proposed. A thorough study of the generalisability, including both interpolation and extrapolation capabilities, of the proposed CNN model is conducted. It is found that the proposed model can achieve significant computational savings while maintaining acceptable accuracy, and its performance is validated in both simulations and actual tunnel cases.

Organic Rankine cycle (ORC) has been considered as one of the most promising technologies in industrial waste heat utilization and power generation. During the actual operation of ORC system, due to the fluctuation of cooling and heat sources, the system operates under off-design conditions in most cases. In this paper, thermodynamic model, heat transfer process description and power equipment model are established to evaluate the operating parameters of ORC for the off-design conditions. Evaporation temperature and condensation temperature are taken as independent parameters for the operation of ORC system. Genetic algorithm is adopted to optimize the independent parameters under the maximum net output power. The results show that the effect of optimizing independent parameters is to make the working fluid at the outlet of the preheater as close as possible to a saturated liquid state, and the working fluid at the inlet of the screw expander should be in a saturated gas state. With the optimal power output increasing by 19.1% for every 5 °C increase in hot water inlet temperature, 9.2% for every 20 kg/s increase in hot water mass flow rate, and 3.9% for every 1 °C decrease in cooling water temperature. The optimization method of off-design operating conditions has good system performance and good engineering application prospects.

BackgroundThe causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown.ObjectiveIn this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR).MethodsWe analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran’s Q tests. FDR correction was used to correct the p-values.ResultsIVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360–6.021, p = 0.006, p_fdr 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367–0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100–0.565, p = 0.001, p_fdr 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results.ConclusionOur study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Abstract Background The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. Methods Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15

The long-trunked elephantids underwent a significant evolutionary stage characterized by an exceptionally elongated mandible. The initial elongation and subsequent regression of the long mandible, along with its co-evolution with the trunk, present an intriguing issue that remains incompletely understood. Through comparative functional and eco-morphological investigations, as well as feeding preference analysis, we reconstructed the feeding behavior of major groups of longirostrine elephantiforms. In the Platybelodon clade, the rapid evolutionary changes observed in the narial region, strongly correlated with mandible and tusk characteristics, suggest a crucial evolutionary transition where feeding function shifted from the mandible to the trunk, allowing proboscideans to expand their niches to more open regions. This functional shift further resulted in elephantids relying solely on their trunks for feeding. Our research provides insights into how unique environmental pressures shape the extreme evolution of organs, particularly in large mammals that developed various peculiar adaptations during the late Cenozoic global cooling trends.

Introduction: The gastrointestinal tract is integral to defending against external contaminants, featuring a complex array of immunological, physical, chemical, and microbial barriers. Mycotoxins, which are toxic metabolites from fungi, are pervasive in both animal feed and human food, presenting substantial health risks.Methods: This review examines the pharmacological, toxicological, and microbiological impacts of natural products on mycotoxicosis, with a particular focus on the gut-x axis. The analysis synthesizes current understanding and explores the role of natural products rich in polysaccharides, polyphenols, flavonoids, and saponins. Results: The review highlights that mycotoxins can disrupt intestinal integrity, alter inflammatory responses, damage the mucus layer, and disturb the bacterial balance. The toxins' effects are extensive, potentially harming the immune system, liver, kidneys, and skin, and are associated with serious conditions such as cancer, hormonal changes, genetic mutations, bleeding, birth defects, and neurological issues. Natural products have shown potential anticancer, anti-tumor, antioxidant, immunomodulatory, and antitoxic properties.Discussion: The review underscores the emerging therapeutic strategy of targeting gut microbial modulation. It identifies knowledge gaps and suggests future research directions to deepen our understanding of natural products' role in gut-x axis health and to mitigate the global health impact of mycotoxin-induced diseases.

Abstract Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan‐based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti‐inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post‐MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation‐targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.

The Sustainable Development Goals (SDGs) reflect the shift in global economic conversation toward inclusive growth. The growth can promote inclusivity and widespread sharing of its advancements by concentrating on four key dimensions. (a) Equality of opportunity, (b) sharing prosperity, (3) environmental sustainability/climate adaptation, and (4) macroeconomic stability. We used the Kao cointegration test to study how certain variables are connected over a long period. The relationship between CO2 and GDP per capita, renewable energy and tourism, improved water and sanitation, and access to power all have a positive feedback effect on each other. Based on FMOLS's findings, a 1 % increase in Inclusive growth leads to a 0.342 % (Model 1) and 0.258 % (Model 3) increase in CO2 emissions. An increase of 1 percent in energy consumption per person resulted in a rise of 1.343 % in CO2 emissions in Case 1, 0.524 % in Case 2, and 0.618 % in Case 3. Increasing the tourism sector's proportion of total exports by just one percent will reduce CO2 emissions by 0.221 % (case 1) and 0.234 % (case 3). Based on CCR findings, a 1 % improvement in inclusive growth leads to a 0.403 %

East Asia, being the evolutionary center of Coelodonta, offers a unique opportunity to explore the spatiotemporal paleoecologies of this genus. This study utilized bulk and serial stable carbon and oxygen isotope analyses on the Coelodonta nihowanensis and other ungulates from the Longdan fauna as well as two modern goats in the Linxia Basin, aiming to explore the paleoecology of C. nihowanensis at the periphery of the Tibetan Plateau during the Early Pleistocene. The isotopic results of these mammals indicated that C3 vegetation was possibly a major component of the local environment in the Linxia Basin, which was influenced by a seasonal summer monsoon. C. nihowanensis specimens in the Longdan fauna were possibly mixed feeders, as indicated by the wide distribution of their δ13C values and the intermediate δ18O values compared to other coexisting ungulates. Moreover, the comparison of the δ13C and δ18O values of similar taxa from the Linxia and Nihewan basins has revealed spatiotemporal differences in the paleoclimate and paleoenvironments of these two regions throughout the Early Pleistocene. This provides a holistic framework for understanding the paleoecology of the C. nihowanensis. The isotopic results of the C. nihowanensis in the Linxia and Nihewan basins suggested varied foraging ecologies across different sites and time spans during the Early Pleistocene. This underscores the adaptability of the C. nihowanensis to diverse environments from west to east in northern China. By scrutinizing the evolutionary ecological history of the woolly rhinoceroses from its ancestor, Coelodonta thibetana, to its final form, Coelodonta antiquitatis, this study sheds light on the ecological adaptation of this genus from the Pliocene to Late Pleistocene, spanning its migration from the Tibetan Plateau to northern Eurasia.

The restorative benefits of urban green spaces (UGSs) have been supported by many studies. Eight perceived sensory dimensions (PSDs) are regarded as a tool to classify green spaces based on perception. However, little attention has been given to the effects of landscape characteristics (LCs) on the perceived restorativeness (PR) of green spaces. Thus, this study aims to clarify this relationship using the eight PSDs. The research collected information, via video stimulus, from 30 participants on the restorative experiences of urban green parks, according to the eight kinds of PSDs. The skin conductance level obtained via biosensors was used to measure the PR. The subjective satisfaction evaluation of 10 LCs was further obtained using a 5-point Likert scale. The data were analyzed using correlation and regression analyses. The results show that the UGSs with dominant “serene,” “open,” and “sheltered” PSDs are rated highest for restoration. Furthermore, the findings identify the significant factors affecting the restoration of green spaces using different PSDs. In green spaces controlled by PSD, scene, vegetation, water features, and disturbances are more reliable predictors for restoration. The results indicate how different PSD spaces can be distributed in green urban planning and provide key points for designing each PSD for restoration. The use of physiological indexes rather than subjective feelings provides an alternative for demonstrating the restorative benefits of the environment. However, before it can officially be used by designers, more research is needed.

AbstractContext Plastics can break down into millions of microplastic (MPs, < 5 mm) particles in the soil and ocean. These MPs can then affect the function of the reproductive system. There is currently no effective solution to this problem aside from traditional Chinese medicine. We have previously used Yishen Tongluo formula (YSTL) to treat sperm DNA damage caused by some toxic substances.Objective To investigate the mechanism underlying the repair of mouse sperm DNA fragmentation caused by polystyrene microplastics by YSTL.Materials and methods An animal model of polystyrene microplastic (PS-MP)-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice PS-MPs at 1 mg/d and treated with YSTL at 11.89, 23.78 and 47.56 g/kg, respectively, for 60 days. The Sperm DNA fragmentation index (DFI) of each group was detected and compared. The target genes of YSTL identified by transcriptomic and proteomic analyses were validated by qRT-PCR and western blotting.Results The DFI of the PS group (20.66%) was significantly higher than that of the control group (4.23%). The medium and high doses of the YSTL group (12.8% and 11.31%) exhibited a significant repairing effect. The most enriched pathway was PI3K/Akt. TBL1X, SPARC, hnRNP0, Map7D1, Eps8 and Mrpl27 were screened and SPARC was validated.Discussion and conclusions The precise mechanism by which YSTL inhibits PD-MPs DNA damage may be associated with the PI3K/Akt pathway and SPARC. It provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by MPs.

Abstract Silver nanoparticles (AgNPs) have durable and remarkable antimicrobial effects on pathogenic microorganisms, such as bacteria and fungi, in dental plaques. As such, they are widely added to dental restoration materials, including composite resins, denture bases, adhesives, and implants, to solve the problems of denture stomatitis, peri-implant inflammation, and oral infection caused by the long-term use of these dental restoration materials. However, AgNPs can be absorbed into the blood circulatory system through the nasal/oral mucosa, lungs, gastrointestinal tract, skin, and other pathways and then distributed into the lungs, kidneys, liver, spleen, and testes, thereby causing toxic injury to these tissues and organs. It can even be transported across the blood-brain barrier (BBB) and continuously accumulate in brain tissues, causing injury and dysfunction of neurons and glial cells; consequently, neurotoxicity occurs. Other nanomaterials with antibacterial or remineralization properties are added to dental restoration materials with AgNPs. However, studies have yet to reveal the neurotoxicity caused by dental restoration materials containing AgNPs. In this review, we summarize the application of AgNPs in dental restoration materials, the mechanism of AgNPs in cytotoxicity and toxic injury to the BBB, and the related research on the accumulation of AgNPs to cause changes of neurotoxicity. We also discuss the mechanisms of neurotoxicity caused by AgNPs and the mode and rate of AgNPs released from dental restorative materials added with AgNPs to evaluate the probability of neurotoxic injury to the central nervous system (CNS), and then provide a theoretical basis for developing new composite dental restoration materials. Graphical Abstract Mechanism of neurotoxicity caused by AgNPs: AgNPs in the blood circulation enter the brain tissue after being transported across the BBB through transendothelial cell pathway and paracellular transport pathway, and continuously accumulate in brain tissue, causing damage and dysfunction of neurons and glial cells which ultimately leads to neurotoxicity. The uptake of AgNPs by neurons, astrocytes and microglia causes damage to these cells. AgNPs with non-neurotoxic level often increases the secretion of a variety of cytokines, up-regulates the expression of metallothionein in glial cells, even up-regulates autophagy and inflammation response to protect neurons from the toxic damage of AgNPs. However, the protective effect of glial cells induced by AgNPs exposure to neurotoxic levels is insufficient, which leads to neuronal damage and dysfunction and even neuronal programmed cell death, eventually cause neurotoxicity.

Abstract Background Tumor necrosis factor receptor-associated factor 3 (TRAF3) has specific regulatory effects on a wide range of diseases, including tumors. However, the effect and mechanism of TRAF3 on lung adenocarcinoma (LUAD) are still unknown. The aim of the present study was to make clear the role and potential mechanism of TRAF3 in LUAD. Methods TIMER2.0 database and western blot were applied to detect the expression of TRAF3 in lung adenocarcinoma tissue. Kaplan-Meier Plotter database was utilized to explore the effect of TRAF3 on the clinical prognosis of lung adenocarcinoma patients. Specific siRNA was used to inhibit the expression of TRAF3 in LUAD cells (A549 and H1299). CCK-8 and EdU assays were performed for assessing LUAD cells proliferation. Wound healing assay and transwell assay were performed for determining cells migration. CCK-8 assay was used to assess the response of the LUAD cells to paclitaxel. TIMER2.0 bioinformatics and western blot were employed to detect the effects of TRAF3 on pyroptosis in LUAD. Results TRAF3 was highly expressed in lung adenocarcinoma tissues and cell lines. Patients with TRAF3 hyperexpression had a good prognosis compared to those with lower expression. TRAF3 inhibition notably induced proliferation and migration of LUAD cells. Inhibition of TRAF3 also weakened the sensitivity of LUAD cells to paclitaxel. Moreover, bioinformatics results showed that TRAF3 was positively correlated with the expression of pyroptosis-related genes in LUAD. Western blot assays showed that TRAF3 inhibition visibly decreased the expression of apoptosis-associated speck-like protein (ASC), cleaved caspase-1 and matured- IL-1β. Conclusions Inhibition of TRAF3 promotes the proliferation and migration of LUAD cells, and reduces the sensitivity of LUAD cells to paclitaxel. The effects of TRAF3 on LUAD cells were mediated in part by caspase-1-dependent pyroptosis.

The communication mechanism of the gut–lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut–lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells.

Recent research indicates that exposure to green space may have positive effects on the mental health of students, potentially mediated by factors such as environmental satisfaction and social cohesion. However, the specific impact of green space exposure on students’ mental health during the COVID-19 campus lockdowns unexplored. To investigate this relationship, a survey was conducted via social media among 346 current students residing on a locked-down campus, assessing their mental well-being, green space satisfaction, social environment satisfaction, subjective exposure and objective exposure to green space. A structural equation model (SEM) was employed to examine the relationships among various dimensions of green space exposure, satisfaction and students’ mental well-being. The findings indicate that subjective exposure to green space has a positive impact on mental well-being and indirectly through social environment satisfaction. Additionally, objective exposure could indirectly influence mental well-being through green space satisfaction and social environment satisfaction.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal anomalies (CLOVES) constitute a rare overgrowth disorder resulting from a mosaic function-acquiring mutation in the PIK3CA gene. Targeted drugs for the PI3K-AKT signaling pathway remain under clinical trial and surgery is commonly used to meet both aesthetic and functional requirements for CLOVES patients. We report here the course and experience of a male patient treated at our institution for up to 13 years. The course of treatment consisted of nine anhydrous ethanol sclerotherapy procedures and two segmental trunk mass resections. After undergoing sequential treatment, the patient experienced improved thoracic deformity and scoliosis, enabling him to grow and develop normally.

As coal mines shift from shallow to deeper excavation, the number of mines facing the risk of rock burst disasters is gradually increasing. Rockburst, with their characteristics of vibration, suddenness, complexity, and unpredictability, make it increasingly difficult to prevent and control these disasters. Therefore, the challenges of preventing and controlling rock burst disasters are becoming more and more severe. This paper, based on the system-theoretic accident model and processes (STAMP) theory, extracts the causal factors affecting coal mine rock burst accidents. Using the interpretative structural modeling (ISM) and decision-making trial and evaluation laboratory (DEMATEL) method, the accident-causing factors are quantitatively assigned. By constructing model equations and drawing causal loop diagrams and stock-flow diagrams, the event is dynamically simulated and early warnings are issued. The results show that the control defects leading to the accident are analyzed from the perspectives of the government level, management level, grassroots level, physical layer, and the dynamic process of the accident. In the short term, safety investment in grassroots operations is the most effective control. In the long run, the most effective measure is for the management level to strengthen its supervisory work. By changing the input ratios of various variables, it can be seen that different variables in the system dynamics (SD) model have different impacts on coal mine rock burst accidents. It is necessary to continuously strengthen the implementation of the safety responsibility system, improve the work efficiency of the government and management level, and enhance the timeliness of emergency decision-making.

Objectives: To examine the association of changes in plant-based diet consumption with all-cause mortality among older adults in China. Design: Cohort study. Setting: This cohort study of 11 years used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a long-term, nationwide survey covering 23 provinces in China. Participants: A total of 7843 older participants aged ≥60 years were included in this study. Measurements: Changes in plant-based diets consumption (2008–2011) were assessed by 3 graded plant-based diet indices, including an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). The main outcome was all-cause mortality. Multivariable-adjusted Cox proportional-hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of mortality for changes in PDI, hPDI, and uPDI. Results: A total of 7843 participants (mean [SD] age, 82.2 [10.9] years; 3588 [45.7%] men) were included in this study. During a median (IQR) of 9 (5–10) years of follow-up, 3749 deaths were documented. Compared with older adults whose plant-based diet indices were relatively stable, older adults with the greatest decrease (quintile 1) in PDI, hPDI, and uPDI had respectively 32% (95% CI, 19%–47%) higher, 21% (95% CI, 9%–33%) higher, and 10% (95% CI, 4%–21%) lower risk of death. Compared with older adults whose diet indices were relatively stable, older adults with the greatest increase (quintile 5) in uPDI had a 13% higher risk of death (95% CI, 1%–21%), while no significant associations of the increased PDI and hPDI with all-cause mortality were observed. Conclusion: Maintaining the consumption of overall and healthful plant-based diets, and decreasing the consumption of an unhealthful plant-based diet can be beneficial in preventing or delaying premature death among Chinese older adults.

Sustaining or enhancing nature’s contributions to people (NCPs) requires a comprehensive understanding of both nature’s contributions and people’s needs. However, the 2 aspects for water-related NCPs are spatially mismatched. We introduced an assessment framework for water-related NCPs from a spatial flow perspective, considering the local nature’s contributions assessed using the InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) model, as well as people’s needs in the downstream assessed via a distance decay method. We assessed 3 water-related NCPs’ spatial distribution and correlation on the Loess Plateau from 2000 to 2020, where a large-scale ecological restoration was implemented that may affect downstream people. The results showed that NCP6 (downstream needs from water yield) showed no increasing trend in the majority watersheds over the past 20 years, in contrast to NCP7 (downstream needs from water purification) and NCP8 (downstream needs from soil conservation). There are spatial synergies among NCP6, NCP7, and NCP8. From 2000 to 2020, the spatial synergy between NCP7 and NCP8 increased while decreased between other NCPs. The temporal dynamics of NCP6 and NCP8 showed a trade-off, while NCP6 and NCP7 showed a synergy. NCP7 and NCP8, in turn, showed a transition from synergy to trade-off. Guided by nature’s contributions and people’s needs, we proposed 3 ecological measures: thinning and intermediate cutting measures, control nonpoint source pollution, and soil and water conservation projects to promote ecological restoration. This assessment can offer multifunctional guidance for planning ecological conservation and restoration in the upstream based on people’s needs in the downstream.

As a member of Aceratheriinae, the genus Plesiaceratherium in Europe is widely distributed and highly diverse. However, only one species of Plesiaceratherium (i.e., P. gracile) exists in China with a discontinuous distribution range. Recently, we have discovered new materials of Plesiaceratherium in the lower layers of the Zhang’enbao Formation exposed in Miaoerling in Tongxin County, China. The new materials are well-preserved and can be separated from other Plesiaceratherium species by the following combination of features: the long and generally flat skull, with closed frontoparietal crests; the deep nasal notch at the level of P4; the high supraorbital margin, with its anterior margin at the level of the M1/M2 boundary; the medium-sized upper I1, with an oval abraded surface; the semi-molarized upper premolars with the protocone and hypocone joined by a lingual bridge; the strong constrictions of protocone on the upper molars; the absent buccal cingulum on upper cheek teeth; the cheek teeth are covered by cement on the buccal walls; the convex base of mandibular corpus; the inclined backward ramus; and the mandibular foramen above the teeth neck. Based on the combination of characteristics and phylogenetic analysis, we herein establish the new species as Plesiaceratherium tongxinense sp. nov. living in the late Early Miocene. Phylogenetic analysis reveals that P. tongxinense is in the basal position of the genus Plesiaceratherium, providing more detailed morphological characteristics of the plesiaceratheres.

Abstract Background and Objectives Surgery is an essential treatment for non‐distant metastatic cutaneous melanoma (NMCM). We aim to construct and validate prognostic nomograms based on surgical approaches and the clinicopathological characteristics of NMCM patients. Methods Data of patients diagnosed with cutaneous melanoma from 2004 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Two online nomograms were constructed to predict the 3, 5‐year melanoma‐specific survival (MSS) for NMCM patients based on the surgical approaches. These nomograms were evaluated by the dynamic Harrell's concordance index (C‐index), decision curve analysis and clinical impact curve. Both internal and external data verification were conducted. Results A total of 14,091 NMCM cases were included in this study. The C‐index of the nomograms for the excisional surgery group and amputation group were 0.818 and 0.806, respectively, and 0.763 and 0.731, respectively, in our hospital data validation. After internal and bootstrap verification, our two nomograms showed good accuracy and practicality. Conclusion NMCM patients exhibited equal survival rates independent of resection margin size, while those who needed amputation had worse survival rates. We generated two online nomograms distinguished by surgical approach to predict NMCM patient survival based on clinicopathological characteristics.

Abstract Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen. Due to its specific structural, biological and physicochemical properties, collagen hydrolysates have been explored as a multifunctional antioxidant in the biomedical field. In this review, we summarize recent advances in antioxidant collagen hydrolysates development. Initially, the preparation process of antioxidant collagen hydrolysates is introduced, including the production and separation methods. Then the effects and the mechanisms of amino acid composition and collagen peptide structure on the antioxidant activity of collagen hydrolysates are reviewed. Finally, the applications of antioxidant collagen hydrolysates in biomedical domains are summarized, with critical discussions about the advantages, current limitations and challenges to be resolved in the future. Graphical abstract

In the last years there has been a booming in the development of biological pharmaceuticals, and various nanoparticle delivery systems have been developed to overcome biological barriers to maximize the therapeutic potentials. Especially, when these drug-loaded nanoparticle systems arrive at the target cells, they must be successfully internalized into the cells, followed by the endosome escape, to release the payload in the cytoplasm. This is crucial so that the payloads are not degraded in the endosome (around pH 6.8–6.0) or lysosome (around pH 4.5). Considering the acid environment of the endosome, several studies have shown the design of different acid-labile nanoparticle delivery systems attempting to achieve endosome escape by, for example, endosomal rupture, membrane destabilization, and membrane fusion. In this mini-review, we summarize current designs in acid-labile chemical bonds for endosome escape of nanosystems. First, we briefly introduce the structural design of acid-labile nanoparticles and their endosomal escape mechanisms. Then, we review recent research work on the topic, highlighting how the nanoparticle designs can be used in endosome escape for different biomedical applications. Finally, we discuss the challenges and future perspectives in this field.

High-entropy materials, for both complexity in structure and superiority in performance, have been widely confirmed to be one possible kind of advanced electrocatalyst. Significant efforts have been dedicated to modeling the atomic-level details of high-entropy catalysts to improve the viability for bottom-up design of advanced electrocatalysts. In this review, first, we survey developments in various modeling methods that are based on density functional theory. We review progress in density functional theory simulations for emulating different high-entropy electrocatalysts. Then, we review the advancements in simulations of high-entropy materials for electrocatalytic applications. Finally, we present prospects in this field.Abbreviations: HEMs: high-entropy materials; CCMs: compositionally complex materials; DFT: density functional theory; LDA: local density approximation; GGA: generalized gradient approximation; VASP: Vienna Ab initio simulation package; ECP: effective core potential; PAW: projector-augmented wave potential; VCA: virtual crystal approximation; CPA: coherent potential approximation; SQS: special quasi-random structures; SSOS: small set of ordered structures; SLAE: similar local atomic environment; HEAs: high-entropy alloys; FCC: face-centered cubic; BCC: body-centered cubic; HCP: hexagonal close-packed; ORR: oxygen reduction reaction; OER: oxide evolution reaction; HER: hydrogen evolution reaction; RDS: rate-limiting step; AEM: adsorbate evolution mechanism; LOM: lattice oxygen oxidation mechanism; HEOs: high-entropy oxides; OVs: oxygen vacancies; PDOS: projected densities of states; ADR: ammonia decomposition reaction; NRR: nitrogen reduction reaction; CO2RR: CO2 reduction reaction; TMDC: transition metal dichalcogenide; TM: transition metal; AOR: alcohol oxidation reaction; GOR: glycerol oxidation reaction; UOR: urea oxidation reaction; HEI: high-entropy intermetallic.

Ischemic heart disease (IHD) remains a major global health concern, with ischemia-reperfusion injury exacerbating myocardial damage despite therapeutic interventions. In this study, we investigated the role of tropomyosin 3 (TPM3) in protecting cardiomyocytes against hypoxia-induced injury and oxidative stress. Using the AC16 and H9c2 cell lines, we established a chemical hypoxia model by treating cells with cobalt chloride (CoCl2) to simulate low-oxygen conditions. We found that CoCl2 treatment significantly upregulated the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in cardiomyocytes, indicating the successful induction of hypoxia. Subsequent morphological and biochemical analyses revealed that hypoxia altered cardiomyocyte morphology disrupted the cytoskeleton, and caused cellular damage, accompanied by increased lactate dehydrogenase (LDH) release and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity, indicative of oxidative stress. Lentivirus-mediated TPM3 overexpression attenuated hypoxia-induced morphological changes, cellular damage, and oxidative stress imbalance, while TPM3 knockdown exacerbated these effects. Furthermore, treatment with the HDAC1 inhibitor MGCD0103 partially reversed the exacerbation of hypoxia-induced injury caused by TPM3 knockdown. Protein–protein interaction (PPI) network and functional enrichment analysis suggested that TPM3 may modulate cardiac muscle development, contraction, and adrenergic signaling pathways. In conclusion, our findings highlight the therapeutic potential of TPM3 modulation in mitigating hypoxia-associated cardiac injury, suggesting a promising avenue for the treatment of ischemic heart disease and other hypoxia-related cardiac pathologies.

Background: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. Methods: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. Results: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (β = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (β = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. Conclusions: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.

ABSTRACT QingXiaoWuWei decoction (QXWWD) exerts a prominent therapeutic effect on the methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia model in mice; however, its pharmacological mechanisms remain unclear. This study aimed to investigate the underlying pharmacological mechanisms of QXWWD in MRSA-induced pneumonia. In the present study, 62 compounds were identified using high-resolution mass spectrometry. Network analysis, leveraging mass spectrometry, pinpointed the infection-linked, immunity-associated, and inflammation-related pathways as predominant targets. QXWWD significantly alleviated MRSA-induced pneumonia in mice and decreased the levels of pro-inflammatory cytokines and chemokines. 16S ribosomal RNA (16S rRNA) sequencing revealed that QXWWD regulated gut microbiota composition in mice with MRSA-induced pneumonia, which correlated with the enrichment of certain short-chain fatty acids (SCFAs)-producing strains. Further analysis with targeted metabolomics confirmed that the acetic, propionic, and butyric acid levels in the mice’s serum were elevated significantly after QXWWD treatment. The fecal microbiota transplantation experiment suggested that gut microbiota from QXWWD-treated mice and SCFAs treatment may alleviate MRSA-induced pneumonia. Additionally, the untargeted metabolomic analysis further demonstrated that metabolic remodeling is significantly regulated by the QXWWD, particularly by the enhancement of the citrate cycle. In the case of QXWWD treatment, global transcriptome profiling revealed that genes, such as NLRP12 and CYP1A1, associated with macrophage antibacterial and immune activity, were downregulated. The results revealed that QXWWD regulated metabolic remodeling and macrophage gene expression network via the microbiota-SCFAs axis and thus alleviated MRSA-induced pneumonia in mice. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.

Fritillaria taipaiensis P. Y. Li is the most suitable species planted at low altitudes among other species used as Tendrilleaf Fritillary Bulb, whose seeds embracing the morphological and physiological dormancy need to experience a long-dormant time from sowing to germination. In this study, the developmental changes of F. taipaiensis seeds during dormancy period were observed by morphological and anatomical observation, and the cause of long-term dormancy of seeds was discussed from the perspective of embryonic development. The process of embryonic organogenesis was revealed during the dormancy stage by the paraffin section. The effects of testa, endosperm and temperature on dormant seeds were discussed. Furthermore, we found that the mainly dormant reason was caused by the morphological dormancy, which accounted for 86% of seed development time. The differentiation time of the globular or pear-shaped embryo into a short-rod embryo was longer, which was one of the chief reasons for the morphological dormancy and played an important role in embryonic formation. Testa and endosperm with mechanical constraint and inhibitors involved in the dormancy of F. taipaiensis seeds. The seeds of F. taipaiensis, the average ambient temperature of 6–12°C for morphological dormancy and 11–22°C for physiological dormancy, were unsuitable for seed growth. Therefore, we suggested that the dormancy time of F. taipaiensis seeds could be shortened by shortening the development time of the proembryo stage and stratification for the different stages of dormancy.

Soil salinization threatening natural and agricultural production challenges global food security. Halophytes are of great interest in soil desalinization in recent years; yet, there is a lack of a comprehensive quantitative overview of biotic and abiotic factors for halophytes’ desalinization performance across global scales. Here, a meta-analysis was conducted using 400 observations from 53 peer-reviewed studies to assess desalinization by halophytes in relation to 27 variables. Results showed that soil salinity was significantly decreased in halophytes field on average by 37.7% compared to control on a global scale (p < 0.05). Desalinization performance was better in cold and hot regions than in temperate regions, in dry regions than in wet regions, in alkaline saline soils than in neutral saline soils, and in conditions with low sand content than high sand content. Under aboveground harvest treatment, desalinization increased with the years of cultivation, while no trends were detected under no harvest treatment, indicating the importance of aboveground accumulation. Desalinization was not related to soil CaCO3 content but was accompanied by soil structure improvement, nutrition enrichment, and microbe propagation, implying other root-microbe-soil interactions rather than CaCO3 dissolution play important roles. Shoot biomass could be used as an indicator of the desalinization performance, and the performance would not be decreased due to the high uptake selectivity for K+ over Na+. Notably, desalinization was similar in the pot experiments and field experiments, but pot experiments would magnify the contribution of aboveground salt accumulation to desalinization. Our findings can help to expand the applicability and efficiency of halophytes for sustainable agricultural development in saline soils.

ObjectiveSchizophrenia is a serious mental disease that brings not only serious burdens to patients and their families but also serious challenges to society. More research is needed to find better drugs to treat schizophrenia. This meta-analysis investigated the efficacy and safety of sodium nitroprusside in the treatment of schizophrenia.MethodsRandomized controlled trials comparing the efficacy and safety of sodium nitroprusside in the treatment of schizophrenia were searched via English and Chinese databases. The outcomes, including the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS), were recorded. RevMan 5.3 was used for the meta-analysis.ResultsA total of six randomized controlled trials (174 patients) were included. The overall quality of the included studies was good. No statistically significant benefit of sodium nitroprusside over placebo was found when combined PANSS total and BPRS-18 (95% CI: −1.40, 0.02). Except for PANSS positive (95% CI: −1.86, −0.01), there was no significant difference in the scale score after sodium nitroprusside treatment compared with the control group in PANSS total (95% CI: −4.93, 0.23), PANSS general (95% CI: −2.53, 1.33), and PANSS negative (95% CI: −4.44, 0.89). The results of the sensitivity analysis excluding the study with clinical heterogeneity showed that sodium nitroprusside had no statistical benefit for the score of PANSS positive (95% CI: −2.19, 0.46). Moreover, there was also no significant difference in the BPRS-18 (95% CI: −3.23, −0.43).ConclusionWe conservatively believe that sodium nitroprusside does not alleviate the symptoms of schizophrenia compared with placebo. The subjects tolerated sodium nitroprusside well. Our findings provide a new idea for researchers to explore and solve the drug treatment of schizophrenia.

Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.

Abstract Background Recent advances in telecommunications technology have raised the possibility of telehealth intervention delivering cardiac telerehabilitation, which may provide the efficacy of health services in patients after percutaneous coronary intervention (PCI). This study aimed to investigate the effects of home-based cardiac telerehabilitation (HBCTR) in patients undergoing PCI. Methods We performed a comprehensive search of the following electronic databases: PubMed, Cochrane Central, Web of Science, Embase, CNKI, and WANFANG. For the prespecified outcomes, the primary outcomes were results of physical function (the six-minute walking test, 6MWT) and quality of life (QoL) of the participants. The secondary outcomes were results of (1) blood pressure; (2) full lipid profile (3) reliable assessment of anxiety and depression in patients. Results All studies were conducted between 2013 and 2022, and a total of 5 articles could be included in the quantitative meta-analysis. The results showed that there was a statistically significant difference between the HBCTR intervention group and the control group in 6WMT (MD 16.59, 95%CI 7.13 to 26.06, P = 0.0006), but there was no difference in QoL (SMD − 0.25, 95%CI − 1.63 to 1.13, P = 0.73). According to the fixed effects model, there was a statistically significant difference between the HBCTR group versus the control group (MD − 2.88, 95%CI − 5.19 to − 0.57, P = 0.01), but not in diastolic blood pressure. Likewise, significant improvements of triglycerides and in low-density lipoprotein cholesterol were observed in HBTCR groups, but no significant differences were observed regarding total cholesterol and high-density lipoprotein cholesterol. Conclusion This systematic review and meta-analysis have proven that the HBCTR is one of the promisingly effective cardiac rehabilitation strategies that improve cardiorespiratory fitness and reduce cardiovascular disease risk factors. With the continuous improvement of the telerehabilitation network, it is expected to serve in clinical.

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

One of the major functions of the accessory protein Vif of human immunodeficiency virus type 1 (HIV-1) is to induce the degradation of APOBEC3 (A3) family proteins by recruiting a Cullin5-ElonginB/C-CBFβ E3 ubiquitin ligase complex to facilitate viral replication. Therefore, the interactions between Vif and the E3 complex proteins are promising targets for the development of novel anti-HIV-1 drugs. Here, peptides are designed for the Vif-CBFβ interaction based on the sequences of Vif mutants with higher affinity for CBFβ screened by a yeast surface display platform. We identified two peptides, VMP-63 and VMP-108, that could reduce the infectivity of HIV-1 produced from A3G-positive cells with IC50 values of 49.4 μM and 55.1 μM, respectively. They protected intracellular A3G from Vif-mediated degradation in HEK293T cells, consequently increasing A3G encapsulation into the progeny virions. The peptides could rapidly enter cells after addition to HEK293T cells and competitively inhibit the binding of Vif to CBFβ. Homology modeling analysis demonstrated the binding advantages of VMP-63 and VMP-108 with CBFβ over their corresponding wild-type peptides. However, only VMP-108 effectively restricted long-term HIV-1 replication and protected A3 functions in non-permissive T lymphocytes. Our findings suggest that competitive Vif-derived peptides targeting the Vif-CBFβ interaction are promising for the development of novel therapeutic strategies for acquired immune deficiency syndrome.

Waterfowl populations monitoring is essential for wetland conservation. Lately, deep learning techniques have shown promising advancements in detecting waterfowl in aerial images. In this paper, we present performance evaluation of several popular supervised and semi-supervised deep learning models for waterfowl detection in aerial images using four new image datasets containing 197,642 annotations. The best-performing model, Faster R-CNN, achieved 95.38% accuracy in terms of mAP. Semi-supervised learning models outperformed supervised models when the same amount of labeled data was used for training. Additionally, we present performance evaluation of several deep learning models on waterfowl classifications on aerial images using a new real-bird classification dataset consisting of 6,986 examples and a new decoy classification dataset consisting of about 10,000 examples per category of 20 categories. The best model achieved accuracy of 91.58% on the decoy dataset and 82.88% on the real-bird dataset.

Unoccupied aerial systems (UASs) may provide cheaper, safer, and more accurate and precise alternatives to traditional waterfowl survey techniques while also reducing disturbance to waterfowl. We evaluated availability and perception bias based on machine-learning-based non-breeding waterfowl count estimates derived from aerial imagery collected using a DJI Mavic Pro 2 on Missouri Department of Conservation intensively managed wetland Conservation Areas. UASs imagery was collected using a proprietary software for automated flight path planning in a back-and-forth transect flight pattern at ground sampling distances (GSDs) of 0.38–2.29 cm/pixel (15–90 m in altitude). The waterfowl in the images were labeled by trained labelers and simultaneously analyzed using a modified YOLONAS image object detection algorithm developed to detect waterfowl in aerial images. We used three generalized linear mixed models with Bernoulli distributions to model availability and perception (correct detection and false-positive) detection probabilities. The variation in waterfowl availability was best explained by the interaction of vegetation cover type, sky condition, and GSD, with more complex and taller vegetation cover types reducing availability at lower GSDs. The probability of the algorithm correctly detecting available birds showed no pattern in terms of vegetation cover type, GSD, or sky condition; however, the probability of the algorithm generating incorrect false-positive detections was best explained by vegetation cover types with features similar in size and shape to the birds. We used a modified Horvitz–Thompson estimator to account for availability and perception biases (including false positives), resulting in a corrected count error of 5.59 percent. Our results indicate that vegetation cover type, sky condition, and GSD influence the availability and detection of waterfowl in UAS surveys; however, using well-trained algorithms may produce accurate counts per image under a variety of conditions.

The progression and metastasis of oral squamous cell carcinoma (OSCC) are highly influenced by cancer stem cells (CSCs) due to their unique self-renewal and plasticity. In this study, data were obtained from a single-cell RNA-sequencing dataset (GSE172577) in the GEO database, and LASSO-Cox regression analysis was performed on 1344 CSCs-related genes to establish a six-gene prognostic signature (6-GPS) consisting of ADM, POLR1D, PTGR1, RPL35A, PGK1, and P4HA1. High-risk scores were significantly associated with unfavorable survival outcomes, and these features were thoroughly validated in the ICGC. The results of nomograms, calibration plots, and ROC curves confirmed the good prognostic accuracy of 6-GPS for OSCC. Additionally, the knockdown of ADM or POLR1D genes may significantly inhibit the proliferation, migration, and invasion of OSCC cells through the JAK/HIF-1 pathway. Furthermore, cell-cycle arrest occurred in the G1 phase by suppressing Cyclin D1. In summary, 6-GPS may play a crucial role in the occurrence and development of OSCC and has the potential to be developed further as a diagnostic, therapeutic, and prognostic tool for OSCC.

Acute T-lymphoblastic leukemia (T-ALL) is a type of leukemia that can occur in both pediatric and adult populations. Compared to acute B-cell lymphoblastic leukemia (B-ALL), patients with T-cell T-ALL have a poorer therapeutic efficacy. In this study, a novel anti-CD7 antibody–drug conjugate (ADC, J87-Dxd) was successfully generated and used for T-ALL treatment. Firstly, to obtain anti-CD7 mAbs, we expressed and purified the CD7 protein extracellular domain. Utilizing hybridoma technology, we obtained three anti-CD7 mAbs (J87, G73 and A15) with a high affinity for CD7. Both the results of immunofluorescence and Biacore assay indicated that J87 (KD = 1.54 × 10−10 M) had the highest affinity among the three anti-CD7 mAbs. In addition, an internalization assay showed the internalization level of J87 to be higher than that of the other two mAbs. Next, we successfully generated the anti-CD7 ADC (J87-Dxd) by conjugating DXd to J87 via a cleavable maleimide-GGFG peptide linker. J87-Dxd also possessed the ability to recognize and bind CD7. Using J87-Dxd to treat T-ALL cells (Jurkat and CCRF-CEM), we observed that J87-Dxd bound to CD7 was internalized into T-ALL cells. Moreover, J87-Dxd treatment significantly induced the apoptosis of Jurkat and CCRF-CEM cells. The IC50 (half-maximal inhibitory concentration) value of J87-Dxd against CCRF-CEM obtained by CCK-8 assay was 6.3 nM. Finally, to assess the antitumor efficacy of a J87-Dxd in vivo, we established T-ALL mouse models and treated mice with J87-Dxd or J87. The results showed that on day 24 after tumor inoculation, all mice treated with J87 or PBS died, whereas the survival rate of mice treated with J87-Dxd was 80%. H&E staining showed no significant organic changes in the heart, liver, spleen, lungs and kidneys of all mice. In summary, we demonstrated that the novel anti-CD7 ADC (J87-Dxd) had a potent and selective effect against CD7-expressing T-All cells both in vitro and in vivo, and could thus be expected to be further developed as a new drug for the treatment of T-ALL or other CD7-expression tumors.

Objective: Viral myocarditis in children (VMCC) is a severe condition that requires effective treatment options. Astragalus membranaceus Injection (AMI) has been widely used for the treatment of VMCC and has shown promising results. In light of this, we conducted an overview of systematic reviews (OoSRs) and meta-analyses of randomized controlled trials (RCTs) to provide a comprehensive summary of the available evidence regarding the efficacy and safety of AMI in treating VMCC. Methods: We conducted a thorough search of 8 databases up until November 18th, 2022 to identify all systematic reviews (SRs) pertaining to the use of AMI for VMCC. We assessed the methodology quality, report quality, and evidence quality of the retrieved SRs using the AMSTAR-2, PRISMA, and GRADE frameworks. For meta-analysis, we used either a fixed-effects or a random-effects model to calculate effect sizes and 95% confidence intervals (CI) with Stata version 12.0, based on the number of original trials. We presented general results in evidence maps utilizing bubble plots. Results: A total of 4 SRs, comprising 115 RCTs and 9048 patients, were determined to be eligible for inclusion in OoSRs. Our findings revealed moderate-certainty evidence that combining AMI with western medicine (WM) improved the effective rate, cure rate and electrocardiogram results, while reducing creatine kinase, creatine kinase-MB, and lactate dehydrogenase levels for VMCC compared to the WM group. Furthermore, combination therapy did not increase adverse drug reactions[RR=0.79, 95%CI (0.44, 1.40), P>0.05] for VMCC. Evidence maps demonstrated that combining AMI with WM was more advantageous for treating VMCC. Conclusion: AMI is a valuable therapeutic option for VMCC, demonstrating remarkable efficacy and a favorable safety profile. However, to confirm these findings and determine the optimal dosing and administration regimens, further prospective studies are necessary. Our work provides a foundation for future research on this topic. While our findings support the effectiveness and safety of combining AMI with WM for treating VMCC, caution should be exercised in interpreting these results due to the quality of the current literature. Larger-scale, well-designed studies are necessary to confirm the results and provide high-quality evidence.To advance the management and outcomes of VMCC within the context of Chinese medicine, our study highlights the need for ongoing research efforts in this area. We believe that additional research will expand our understanding of the mechanisms underlying the effects of AMI and WM on VMCC, and ultimately benefit patients with this condition.

The evaluation of coronary morphology provides important guidance for the treatment of coronary heart disease (CHD). A chaotic Gaussian mutation antlion optimizer algorithm (CGALO) is proposed in the paper, and it is combined with SVM to construct a classification prediction model for Fractional flow reserve (FFR). To overcome the limitations of the original antlion optimizer (ALO) algorithm, the chaotic Gaussian mutation strategy is introduced, which leads to an improvement in its convergence speed and accuracy. To evaluate the proposed algorithm's performance, comparative experiments were conducted on 23 benchmark functions alongside 12 other cutting-edge optimization algorithms. The experimental outcomes demonstrate that the proposed algorithm achieves superior convergence accuracy and speed compared to the alternative comparison algorithms. Additionally, it is combined with SVM and FS to construct a hierarchical FFR classification model, which is utilized to make effective predictions for 84 patients at the affiliated hospital of medical school, Ningbo university. The experimental results demonstrate that the proposed model achieves an average accuracy of 92%. Moreover, it concludes that smoking history, number of lesion vessels, lesion location, diffuse lesions and ST segment changes, and other factors are the most critical indicators for FFR. Therefore, the model that has been established is a new FFR intelligent classification prediction technology that can effectively assist doctors in making corresponding decisions and evaluation plans.

BackgroundIndoor air pollution has been reported to have adverse effects on the eye; however, the health effects of exposure to cooking with solid fuels on visual impairment remain unclear in China. ObjectiveWe aimed to examine the association between cooking with solid fuels and visual impairment, including distance visual impairment (DVI) and near visual impairment (NVI). MethodsData were obtained from the China Health and Retirement Longitudinal Study, a nationwide survey of adults aged over 45 years who were enrolled in 2011 (Wave 1) and followed up in Wave 2 (2013), Wave 3 (2015), and Wave 4 (2018). We used Cox proportional hazards models to determine the association between solid fuels use and visual impairment. Additionally, the impact of switching cooking fuel types on vision function were examined through wave-specific data analysis (Wave 1 and Wave 4). Interaction and subgroup analyses were performed to explore the potential effect modifiers. Data were collected using the stratified multistage random sampling method and further analyzed using SPSS 27.0 and R 4.2.1 statistical software packages. ResultsA total of 9559 middle-aged and older Chinese adults without visual impairment at baseline were included in the study, with 51.2% (n=4914) of the participants reporting that they cooked with solid fuels. During the follow-up period, 2644 (27.5%) and 3130 (32.6%) participants developed DVI and NVI, respectively. Compared with the clean fuel users, participants who cooked with solid fuels had a higher risk of DVI (hazards ratio [HR] 1.38, 95% CI 1.28-1.50) and NVI (HR 1.18, 95% CI 1.10-1.27). In addition, switching the cooking fuel type from clean to solid fuels was associated with an elevated risk of DVI (HR 1.51, 95% CI 1.15-1.98) and NVI (HR 1.39, 95% CI 1.06-1.82) compared to persistently using clean fuels during the follow-up period, although no protective effect of switching from solid to clean fuels on NVI was found (P=.52). In subgroup analysis, we found that cooking with solid fuels increased the risk of DVI in participants younger than 65 years (HR 1.41, 95% CI 1.28-1.55), men (HR 1.45, 95% CI 1.28-1.65), urban residents (HR 1.41, 95% CI 1.08-1.75), and smokers (HR 1.43, 95% CI 1.25-1.64). By contrast, negative effects of cooking with solid fuels on NVI were found in nonsmokers (HR 1.21, 95% CI 1.11-1.33) and urban residents (HR 1.20, 95% CI 1.10-1.37). ConclusionsCooking with solid fuels was associated with an increased risk of visual impairment among middle-aged and older Chinese adults. These findings indicate that promoting the utilization of clean fuels is conducive to reducing the burden of visual impairment for the public.

IntroductionSolar radiation plays a crucial role in the decomposition of litter and the cycling of nutrients. Previous studies have investigated that the net effect of solar radiation on litter decomposition depends on the balance of its facilitative and inhibitory effects on microbial activity; however, a gap in understanding the mechanism by which precipitation affects the net effect of solar radiation and the mechanism of litter decomposition on a global scale was observed.MethodsIn addressing this gap, a comprehensive meta-analysis of 351 data points from 37 published studies was conducted to estimate the sole radiation effect and interactive effect of solar radiation and precipitation on a global scale, as well as how they vary at different precipitation levels. In addition, the importance of influential factors regulating the net effect of solar radiation on litter decomposition was assessed to identify the key drivers of the response of mass loss to solar radiation at different precipitation levels.ResultsOur findings indicated that solar radiation largely regulates litter decomposition, and the direction and magnitude are potentially dependent on the precipitation regime. In addition, solar radiation significantly increased mass loss and decreased the nutrient remaining. Furthermore, the effects of solar radiation on mass loss, C remaining, and N remaining were found to be similar among areas with precipitation levels below 200 and above 800 mm and greater than in areas with precipitation levels between 200-400 mm and 400-800 mm. The effect of solar radiation on CO2 emissions varied from 13.97% when precipitation was below 200 mm to −0.707% when precipitation was between 200 and 400 mm.ConclusionClimatic factors determine the response ratio of mass loss to solar radiation in arid lands, whereas the initial litter characteristics have a great influence on the response of mass loss to solar radiation in ecosystems that are not moisture limited. The effect of precipitation on the photodegradation mechanism of litter was primarily achieved by influencing the decomposition of lignin, and the main effect of solar radiation on litter decomposition will shift from the positive effect of “photopriming” to the negative effect of “microbial inhibition” with the increase of precipitation. Our findings can provide a comprehensive understanding of litter decomposition patterns on a global scale, and our results showed that CO2 emissions from photodegradation will be lessened by precipitation, which is important in predicting CO2 emission and separating sources of CO2 under future increasing precipitation scenarios, particularly in arid lands.

Aiming to address the potential scenario of waste heat recovery from a steam-water dual heat source, this paper proposes the thermo-economic models of split-flow dual-loop organic Rankine cycle (SFD-ORC) and split-flow triple-loop organic Rankine cycle (SFT-ORC) systems. The particle swarm optimization (PSO) algorithm is employed for single-objective optimization of the systems, with the goal of maximizing the net power output. The non-dominated sorting genetic algorithm-II (NSGA-II) algorithm is used to find the Pareto frontier by considering both the maximum net power output and the lowest cost of electricity production. The multi-objective optimization parameters are evaluated using the entropy weight method and TOPSIS method. The results show that the hot water split ratio and hot water outlet temperature of the high-pressure loop are higher in multi-objective optimization compared to single-objective optimization. The net output power of the SFT-ORC system after single-objective optimization can be up to 7.9% higher than that of the SFD-ORC system. From an economic perspective, it is recommended to use the SFD-ORC system at a hot water temperature of 85 °C–90 °C. In order to enhance the economic performance of the system, the steam outlet pressure should be as low as possible within the allowable range.