Application of pervious concrete pavement in the "breathe in-breathe out" design for sponge cities in China.

Sponge city construction is an ideal approach to mitigate the degradation of urban water environments. Among road materials, permeable concrete pavement stands out due to its unique structure that allows rainwater runoff to flow through its pores. This paper analyzes the current application status and the prospect of different permeable pavement designs in China's sponge cities, aiming to offer valuable insights for urban planning and construction. Statistical analysis summarizes the spatial-temporal distribution patterns of urban flooding disasters in China and their causes. By comparing the characteristics and advantages of pervious concrete pavement with traditional concrete pavement, the potential of permeable concrete pavement in sponge city construction is summarized through case studies. The findings highlight that by adjusting the pore size, permeable concrete pavement can collect rainwater while filtering impurities, thereby purifying surface runoff. The range of the pervious coefficient should ideally fall within the range of 4~8 mm/s. In addition, the pavement's large contact area with the air and internal water evaporation contributes to its self-regulating capability, reducing the occurrence of extreme temperatures. Related experiments have shown that from 8 am to 12 pm, pervious concrete pavement can reduce the temperature by approximately 1 °C compared to conventional concrete. From 12 pm to 8 pm, this temperature difference increases to approximately 3 °C. To meet the needs of environmental protection and resource utilization, permeable concrete pavement can serve as an ideal tool to achieve green and low-carbon development.

Hybrid Bonding Bottlebrush Polymers Grafted from a Supramolecular Polymer Backbone.

Bottlebrush polymers, macromolecules consisting of dense polymer side chains grafted from a central polymer backbone, have unique properties resulting from this well-defined molecular architecture. With the advent of controlled radical polymerization techniques, access to these architectures has become more readily available. However, synthetic challenges remain, including the need for intermediate purification, the use of toxic solvents, and challenges with achieving long bottlebrush architectures due to backbone entanglements. Herein, we report hybrid bonding bottlebrush polymers (systems integrating covalent and noncovalent bonding of structural units) consisting of poly(sodium 4-styrenesulfonate) (p(NaSS)) brushes grafted from a peptide amphiphile (PA) supramolecular polymer backbone. This was achieved using photoinitiated electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization in water. The structure of the hybrid bonding bottlebrush architecture was characterized using cryogenic transmission electron microscopy, and its properties were probed using rheological measurements. We observed that hybrid bonding bottlebrush polymers were able to organize into block architectures containing domains with high brush grafting density and others with no observable brushes. This finding is possibly a result of dynamic behavior unique to supramolecular polymer backbones, enabling molecular exchange or translational diffusion of monomers along the length of the assemblies. The hybrid bottlebrush polymers exhibited higher solution viscosity at moderate shear, protected supramolecular polymer backbones from disassembly at high shear, and supported self-healing capabilities, depending on grafting densities. Our results demonstrate an opportunity for novel properties in easily synthesized bottlebrush polymer architectures built with supramolecular polymers that might be useful in biomedical applications or for aqueous lubrication.

Effects of acupuncture for Bell's palsy patients in the acute phase and its impact on facial nerve edema: a study protocol for a randomized, controlled trial.

Background: Bell's palsy is an acute peripheral facial neuropathy, which is one of the most common causes of facial palsy of lower motor neurons. Facial nerve swelling is commonly observed in Bell's palsy. Acupuncture therapy has been widely used in the treatment of Bell's palsy. However, whether acupuncture can be effectively used in the acute stage is still controversial. There are no clinical trials conducted previously to evaluate the effect of acupuncture on facial nerve edema in Bell's palsy patients. The study aims to evaluate the potential efficacy of different acupuncture modalities on Bell's palsy patients in the acute phase, its effect on facial nerve edema, and to preliminarily explore its possible mechanism. Methods and analysis: In this randomized, controlled trial, 165 Bell's palsy patients with unilateral onset within 3 days will be recruited and randomly assigned to either the electroacupuncture group (n = 33), the acupuncture group (n = 33), the sham acupuncture group (n = 33), the blank control group (n = 33), or the acupuncture control group (n = 33) in a 1:1:1:1:1 ratio. The participants will receive 4 weeks of treatment and 8 weeks of follow-up. The five groups of participants will receive the following treatments: A: Electroacupuncture + Medication (prednisone acetate tablets, mecobalamin tablets, and vitamin B1 tablets); B: Acupuncture + Medication; C: Sham Acupuncture + Medication; D: Medication only; and E: Acupuncture only. The primary outcome will be the effectiveness rate of different acupuncture modalities in improving facial nerve function after the intervention period. The secondary outcomes will be the recovery speed, the diameter of the facial nerve, the echo intensity and thickness of facial muscles, blood flow parameters of the facial artery, the serum inflammatory level, safety evaluation, and adverse events. Preliminary exploration of its mechanism of action occurs through inflammation and immune response. The difference between groups will be assessed using repeated measure analysis of covariance (ANCOVA) and trend chi-square. Discussion: The trial will evaluate the efficacy and facial nerve edema of acupuncture for Bell's palsy patients in the acute phase and preliminarily explore its possible mechanism. The results thus may provide evidence for clinical application. Clinical trial registration: https://www.chictr.org.cn/bin/project/edit?pid=133211, identifier ChiCTR2100050815.

A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.

A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation.

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E-mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 J cm⁻2), compared to relevant work reported (up to 60 J cm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial-targeted PDT) from the perspective of pyroptosis, toward the future development of the state-of-the-art form of PDT.

Laparoscopic versus open gastrectomy for nonmetastatic T4a gastric cancer: a meta-analysis of reconstructed individual participant data from propensity score-matched studies.

BACKGROUND: ​The applicability of laparoscopy to nonmetastatic T4a patients with gastric cancer remains unclear due to the lack of high-quality evidence. The purpose of this study was to compare the survival rates of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for these patients through a meta-analysis of reconstructed individual participant data from propensity score-matched studies. METHODS: PubMed, Embase, Web of Science, Cochrane library and CNKI were examined for relevant studies without language restrictions through July 25, 2023. Individual participant data on overall survival (OS) and disease-free survival (DFS) were extracted from the published Kaplan-Meier survival curves. One-stage and two-stage meta-analyses were performed. In addition, data regarding surgical outcomes and recurrence patterns were also collected, which were meta-analyzed using traditional aggregated data. RESULTS: Six studies comprising 1860 patients were included for analysis. In the one-stage meta-analyses, the results demonstrated that LG was associated with a significantly better DFS (Random-effects model: P = 0.027; Restricted mean survival time [RMST] up to 5 years: P = 0.033) and a comparable OS (Random-effects model: P = 0.135; RMST up to 5 years: P = 0.053) than OG for T4a gastric cancer patients. Two-stage meta-analyses resulted in similar results, with a 13% reduced hazard of cancer-related death (P = 0.04) and 10% reduced hazard of overall mortality (P = 0.11) in the LG group. For secondary outcomes, the pooled results showed an association of LG with less estimated blood loss, faster postoperative recovery and more retrieved lymph nodes. CONCLUSION: Laparoscopic surgery for patients with nonmetastatic T4a disease is associated with a potential survival benefit and improved surgical outcomes.

Screening and validation of atherosclerosis PAN-apoptotic immune-related genes based on single-cell sequencing.

Background: Carotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS's PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital. Methods: We introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments. Results: We identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence. Conclusion: We obtained four PANoptosis-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) associated with CAS, laying a theoretical foundation for treating CAS.

A sensitive Ag+-mediated magnetic relaxation and colorimetry dual-mode sensing platform.

To address the relatively low sensitivity of current redox reagent-mediated magnetic relaxation sensing methods, we present a novel Ag+-mediated magnetic sensing platform that enhances the sensitivity by three orders of magnitude. The new sensing platform is based on Ag+-catalyzed oxidation of Mn2+ to KMnO4, accompanied by a distinct color change, which facilitates colorimetric detection. In the case of insufficient Ag+ ions, MnO2 is an additional oxidation product and the KMnO4/MnO2 ratio is dependent on the concentration of Ag+. When combined with a specific quantity of reducing agent, both KMnO4 and MnO2 are reduced to Mn2+ with a large relaxivity, and the concentration of Mn2+ in the resultant solution inversely correlates with the amount of KMnO4 since KMnO4 consumes more reductant during reduction. Consequently, the transverse relaxation rate of the solution exhibits a negative correlation with the Ag+ concentration. Thus, by coupling this Ag+-mediated Mn2+ to KMnO4 transformation with reactions that modulate Ag+ concentration, a dual-mode sensing platform for magnetic relaxation and colorimetry can be realized. Herein, we take H2O2 as an example to verify the detection performance of this sensing platform since H2O2 can oxidize Ag0 in Ag@Fe3O4 nanoparticles to Ag+. Experimental findings demonstrate detection limits of 10 nM and 20 nM for the magnetic relaxation and colorimetry modes, respectively, affirming the excellent sensitivity and the potential practical application of this strategy.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Sampled-Data H∞ Dynamic Output-Feedback Control for NCSs With Successive Packet Losses and Stochastic Sampling.

The problem of sampled-data H∞ dynamic output-feedback control for networked control systems with successive packet losses (SPLs) and stochastic sampling is investigated in this article. The aim of using sampled-data control techniques is to alleviate network congestion. SPLs that occur in the sensor-to-controller (S-C) and controller-to-actuator (C-A) channels are modeled using a packet loss model. Additionally, it is assumed that stochastic sampling follows a Bernoulli distribution. A model is established to capture the stochastic characteristics of both the SPL model and stochastic sampling. This model is crucial as it allows us to determine the probability distribution of the sampling interval between successive update instants, which is essential for stability analysis. An exponential mean-square stability condition for the constructed equivalent discrete-time stochastic system, which also guarantees the prescribed H∞ performance, is established by incorporating probability theory. The desired controller is designed using a step-by-step synthesis approach, which may offer lower design conservatism compared to some existing methods. Finally, our designed approach using a networked F-404 engine system model is validated and its merits relative to existing results are discussed. The proposed method is finally validated by employing a networked model of the F-404 engine system. Furthermore, the advantages of our method are presented in comparison to previous results.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

Edible Long-Afterglow Photoluminescent Materials for Bioimaging.

Confining luminophores into modified hydrophilic matrices or polymers is a straightforward and widely used approach for afterglow bioimaging. However, the afterglow quantum yield and lifetime of the related material remain unsatisfactory, severely limiting the using effect especially for deep-tissue time-resolved imaging. This fact largely stems from the dilemma between material biocompatibility and the quenching effect of water environment. Herein an in situ metathesis promoted doping strategy is presented, namely, mixing ≈10-3 weight ratio of organic-emitter multicarboxylates with inorganic salt reactants, followed by metathesis reactions to prepare a series of hydrophilic but water-insoluble organic-inorganic doping afterglow materials. This strategy leads to the formation of edible long-afterglow photoluminescent materials with superior biocompatibility and excellent bioimaging effect. The phosphorescence quantum yield of the materials can reach dozens of percent (the highest case: 66.24%), together with the photoluminescent lifetime lasting for coupes of seconds. Specifically, a long-afterglow barium meal formed by coronene salt emitter and BaSO4 matrix is applied into animal experiments by gavage, and bright stomach afterglow imaging is observed by instruments or mobile phone after ceasing the photoexcitation with deep tissue penetration. This strategy allows a flexible dosage of the materials during bioimaging, facilitating the development of real-time probing and theranostic technology.

DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration.

OBJECTIVES: The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues. METHODS: Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus. RESULTS: Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis. CONCLUSION: Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

The Function of Termicin from Odontotermes formosanus (Shiraki) in the Defense against Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb) Infection.

Odontotermes formosanus (Shiraki) is a subterranean termite species known for causing severe damage to trees and structures such as dams. During the synergistic evolution of O. formosanus with pathogenic bacteria, the termite has developed a robust innate immunity. Termicin is a crucial antimicrobial peptide in termites, significantly contributing to the defense against external infections. Building upon the successful construction and expression of the dsRNA-HT115 engineering strains of dsOftermicin1 and dsOftermicin2 in our laboratory, this work employs the ultrasonic breaking method to establish an inactivated dsOftermicins-HT115 technological system capable of producing a substantial quantity of dsRNA. This approach also addresses the limitation of transgenic strains which cannot be directly applied. Treatment of O. formosanus with dsOftermicins produced by this method could enhance the virulence of both Bt and Bb to the termites. This study laid the theoretical groundwork for the development of novel termite immunosuppressants and for the advancement and application of termite biological control strategies.

YAP/TAZ activation mediates PQ-induced lung fibrosis by sustaining senescent pulmonary epithelial cells.

Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms of PQ-induced pulmonary fibrosis and whether pulmonary epithelial cell senescence is involved in the process remain elusive. In this study, PQ-induced pulmonary epithelial cell senescence and Hippo-YAP/TAZ activation were observed in both C57BL/6 mice and human epithelial cells. PQ-induced senescent pulmonary epithelial cells promoted lung fibroblast transformation through secreting senescence-associated secretory phenotype (SASP) factors. Yap/Taz knockdown in mice lungs significantly decreased the expression of downstream profibrotic protein Ctgf and senescent markers p16 and p21, and alleviated PQ-induced pulmonary fibrosis. Interfering YAP/TAZ in senescent human pulmonary epithelial cells resulted in decreased expression of the anti-apoptosis protein survivin and elevated level of apoptosis. In conclusion, our findings reveal a novel mechanism by which the involvement of Hippo-YAP/TAZ activation in pulmonary epithelial cell senescence mediates the pathogenesis of PQ-induced pulmonary fibrosis, thereby offering novel insights and potential targets for the clinical management of PQ poisoning as well as providing the mechanistic insight of the involvement of Yap/Taz activation in cell senescence in pulmonary fibrosis and its related pulmonary disorders. The YIN YANG balance between cell senescence and apoptosis is important to maintain the homeostasis of the lung, the disruption of which will lead to disease.

RPA-CRISPR/Cas12a-LFA combined with a digital visualization instrument to detect Toxoplasma gondii in stray dogs and cats in Zhejiang province, China.

Toxoplasma gondii, which causes toxoplasmosis, is prevalent in warm-blooded animals, such as cats, dogs, and humans. T. gondii causes economic losses to livestock production and represents a potential risk to public health. Dogs and cats are common hosts in the epidemiology of toxoplasmosis. The current molecular diagnostic tools for T. gondii infection require high technical skills, a laboratory environment, and complex instruments. Herein, we developed a recombinase polymerase amplification (RPA)-clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a) assay to detect T. gondii. The lowest limit of detection of the assay was 31 copies/µL for the T. gondii B1 gene. In addition, we established a visual RPA-CRISPR/Cas12a lateral flow band assay (RPA-CRISPR/Cas12a-LFA) combined with a digital visualization instrument, which minimized the problem of false-negative results for weakly positive samples and avoided misinterpretation of the results by the naked eye, making the LFA assay results more accurate. The assay established in this study could identify T. gondii within 55 min with high accuracy and sensitivity, without cross-reaction with other tested parasites. The developed assay was validated by establishing a mouse model of toxoplasmosis. Finally, the developed assay was used to investigate the prevalence of T. gondii in stray cats and dogs in Zhejiang province, Eastern China. The positive rates of T. gondii infection in stray cats and dogs were 8.0% and 4.0%, respectively. In conclusion, the RPA-CRISPR/Cas12a-LFA is rapid, sensitive, and accurate for the early diagnosis of T. gondii, showing promise for on-site surveillance. IMPORTANCE: Toxoplasma gondii is a virulent pathogen that puts millions of infected people at risk of chronic disease reactivation. Hosts of T. gondii are distributed worldwide, and cats and dogs are common hosts of T. gondii. Therefore, rapid diagnosis of early T. gondii infection and investigation of its prevalence in stray dogs and cats are essential. Here, we established a visual recombinase polymerase amplification-clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a-assay combined with a lateral flow band assay and a digital visualization instrument. Detailed analyses found that the assay could be used for the early diagnosis of T. gondii without false-negative results. Moreover, we detected the prevalence of T. gondii in stray cats and dogs in Zhejiang province, China. Our developed assay provides technical support for the early diagnosis of T. gondii and could be applied in prevalence surveys of T. gondii in stray dogs and cats.

Development and validation of a nomogram model for all-cause mortality risk in patients with chronic heart failure and atrial fibrillation.

BACKGROUND: As the global aging process continues to accelerate, heart failure (HF) has become an important cause of increased morbidity and mortality in elderly patients. Chronic atrial fibrillation (AF) is a major risk factor for HF. Patients with HF combined with AF are more difficult to treat and have a worse prognosis. The aim of this study was to explore the risk factors for 1-year mortality in patients with HF combined with AF and to develop a risk prediction assessment model. METHODS: We recruited hospitalized patients with HF and AF who received standardized care in the Department of Cardiology at Shengjing Hospital of China Medical University from January 2013 to December 2018. The patients were randomly divided into modeling and internal validation groups using a random number generator at a 1:1 ratio. Multivariate Cox regression analysis was used to identify risk factors for all-cause mortality during a one-year follow-up period. Then, a nomogram was constructed based on the weights of each index and validated. Receiver operating characteristic curve, the area under the curve (AUC), decision curve, and calibration curve analyses for survival were used to evaluate the model's predictive and clinical validities and calibration. RESULTS: We included 3,406 patients who met the eligibility criteria; 1,703 cases each were included in the modeling and internal validation groups. Eight statistically significant predictors were identified: age, sex, New York Heart Association cardiac function class III or IV, a history of myocardial infarction, and the albumin, triglycerides, N-terminal pro-b-type natriuretic peptide, and blood urea nitrogen levels. The AUCs were 0.793 (95% confidence interval: 0.763-0.823) and 0.794 (95% confidence interval: 0.763-0.823) in the modeling and validation cohorts, respectively. CONCLUSIONS: We present a predictive model for all-cause mortality in patients with coexisting HF and AF comprising eight key factors. This model gives clinicians a simple assessment tool that may improve the clinical management of these patients.

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.

Excessive level of dietary insect protein negatively changed growth metabolomic and transcriptomic profiles of largemouth bass (Micropterus salmoides).

Hermetia illucens (HI) meal is a promising substitute for fish meal (FM) in the feeds of farmed fish. However, the impacts of dietary HI meal on largemouth bass (LMB) remain unknown. In this study, we formulated three isonitrogenous and isolipid diets with 0% (HI0, control), 20% (HI20) and 40% (HI40) of FM substituted by HI meal. A total of 270 juvenile largemouth bass with an initial body weight of 10.02 ± 0.03 g were used (30 fish per tank). After an 80-day feeding trial, the fish fed with the HI40 diet demonstrated decreased growth performance and protein efficiency ratio (PER), and increased liver oxidative indices and lipid accumulation compared to the control (P < 0.05). Transcriptomic analysis revealed the effects of high dietary HI meal on liver gene expression. Consistent with the reduced growth and disturbed liver oxidative status, the upregulated genes were enriched in the biological processes associated with protein catabolism and endoplasmic reticulum (ER) stress; while the downregulated genes were enriched in cellular proliferation, growth, metabolism, immunity and maintenance of tissue homeostasis. Differential metabolites in the liver samples were also identified by untargeted metabolomic assay. The results of joint transcriptomic-metabolomic analyses revealed that the pathways such as one carbon pool by folate, propanoate metabolism and alpha-linolenic acid metabolism were disturbed by high dietary HI meal. In summary, our data revealed the candidate genes, metabolites and biological pathways that account for the adverse effects of high HI meal diet on the growth and health of LMB.