Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

CircUGP2 Suppresses Intrahepatic Cholangiocarcinoma Progression via p53 Signaling Through Interacting With PURB to Regulate ADGRB1 Transcription and Sponging miR-3191-5p.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients' prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co-activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR-3191-5p. As a result, ADGRB1 prevents MDM2-mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti-tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

Extending the π-Conjugation of A Donor-Acceptor Covalent Organic Framework for High-Rate and High-Capacity Lithium-Ion Batteries.

Realizing high-rate and high-capacity features of Lihium-organic batteries is essential for their practical use but remains a big challenge, which is due to the instrinsic poor conductivity, limited redox kinetics and low utility of organic electrode mateials. This work presents a well-designed donor-acceptor Covalent Organic Framework (COFs) with extended conjugation, mesoscale porosity, and dual redox-active centers to promote fast charge transfer and multi-electron processes. As anticipated, the prepared cathode with benzo [1,2-b:3,4-b':5,6-b''] trithiophene (BTT) as p-type and pyrene-4,5,9,10-tetraone (PTO) as n-type material (BTT-PTO-COF) delivers impressive specific capacity (218 mAh g-1 and 275 mAh g-1 at 0.2 A g-1 in ether-based and carbonate-based electrolyte respectively) and outstanding rate capability (79 mAh g-1 at 50 A g-1 in ether-based electrolyte and 124 mAh g-1 at 10 A g-1 in carbonate-based electrolyte). Moreover, the potential of BTT-PTO-COF electrode for prototype batteries has been demonstrated by full cells of dual-ion batteries, which attain comparable electrochemical performances to the half cells. Moreover, mechanism studies combining ex-situ characterization and theoratical calculations reveal the efficient dual-ion storage process and facile charge transfer of BTT-PTO-COF. This work not only expands the diversity of redox-active COFs but also provide concept of structure design for high-rate and high-capacity organic electrodes.

Development of an Integrated Disposable Device for SARS-CoV-2 Nucleic Acid Extraction and Detection.

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

Impact of COVID-19 on emotional and behavioral problems among preschool children: a meta-analysis.

The impact of the Coronavirus Disease 2019 (COVID-19) on society is continuous, resulting in negative psychological consequences. Given the vulnerability and sensitivity to the environment among preschool children, their emotional and behavioral problems deserve more attention. The current study aimed to explore the impact of the epidemic on preschool children's mental health by determining the pooled prevalence of emotional and behavioral problems amidst the Coronavirus Disease 2019 pandemic and to reveal potential reasons for variations between studies. Published studies were searched in Embase, PubMed, ProQuest, PsycINFO, Web of Science, CNKI, and Wanfang. Based on the inclusion criteria outlined in this study, a total of 10 studies encompassing 38,059 participants were incorporated. Employing a random-effect model for estimating the prevalence of emotional and behavioral problems, the results revealed a pooled prevalence rate of 24.3% (95% CI, 0.15-0.38; I²=99.9%) among preschool children. This rate surpasses the pre-outbreak prevalence observed in different countries, signifying a detrimental influence of the epidemic on the mental well-being of preschoolers. Therefore, mental health care and recovery are essential for the vulnerable group during and after the public health crisis. Specific emotional and behavioral problems among preschool children are expected to be researched in the future to provide more targeted guidance for intervention.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

Targeting DKK1 enhances the antitumor activity of paclitaxel and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

The Balloon Catheter Method and the End-hole Catheter Method in the Measurement of Hepatic Venous Pressure Gradient: a Comparative Study.

OBJECTIVE: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. METHODS: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. RESULTS: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). CONCLUSION: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.

Metal-Catalyzed Carbon Foams Synthesized from Glucose as Highly Efficient Electromagnetic Absorbers.

This paper introduces a novel method for preparing high-performance, metal-containing carbon foam wave-absorbing materials. The process involves foaming glucose through catalysis by transition metals followed by high-temperature pyrolysis. The resulting carbon foam materials exhibit a highly porous structure, which is essential for their wave-absorption properties. Notably, at a thickness of 2.0 mm, the glucose-derived carbon foam composite catalyzed by Fe and Co (GCF-CoFe) achieved a minimum reflection loss (RLmin) of -51.4 dB at 15.11 GHz, along with an effective absorption bandwidth (EAB) of 5.20 GHz, spanning from 12.80 GHz to 18.00 GHz. These impressive performance metrics indicate that this approach offers a promising pathway for developing low-density, efficient carbon foam materials for wave-absorption applications. This advancement has significant implications for fields requiring effective electromagnetic interference (EMI) shielding, stealth technology, and other related applications, potentially leading to more efficient and lightweight solutions.

Targeted delivery of TGF-ß mRNA to lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta (TGF-ß), to produce transient protein expression in the lower regions of the lung. This study highlights IAJD's potential for precise, effective, and safe delivery of TGF-ß mRNA to the lung. This delivery system offers a promising approach for targeting therapeutics to the specific tissues, a strategy necessary to fill the current clinical gap in treating parenchymal lung injury and disease.

Physical activity promotes brain development through serotonin during early childhood.

Early childhood serves as a critical period for neural development and skill acquisition when children are extremely susceptible to the external environment and experience. As a crucial experiential stimulus, physical activity is believed to produce a series of positive effects on brain development, such as cognitive function, social-emotional abilities, and psychological well-being. The World Health Organization recommends that children engage in sufficient daily physical activity, which has already been strongly advocated in the practice of preschool education. However, the mechanisms by which physical activity promotes brain development are still unclear. The role of neurotransmitters, especially serotonin, in promoting brain development through physical activity has received increasing attention. Physical activity has been shown to stimulate the secretion of serotonin by increasing the bioavailability of free tryptophan and enriching the diversity of gut microbiota. Due to its important role in modulating neuronal proliferation, differentiation, synaptic morphogenesis, and synaptic transmission, serotonin can regulate children's explicit cognitive and social interaction behavior in the early stages of life. Therefore, we hypothesized that serotonin emerges as a pivotal transmitter that mediates the relationship between physical activity and brain development during early childhood. Further systematic reviews and meta-analyses are needed to specifically explore whether the type, intensity, dosage, duration, and degree of voluntariness of PA may affect the role of serotonin in the relationship between physical activity and brain function. This review not only helps us understand the impact of exercise on development but also provides a solid theoretical basis for increasing physical activity during early childhood.

Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an "ion cocktail therapy" is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Insight into the surface discharge cold plasma efficient inactivation of Pseudomonas fluorescens in water based on exogenous reactive oxygen and nitrogen species: Synergistic mechanism and energy benefits.

As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-log10Pseudomonas fluorescens and application of •OH and 1O2 scavengers significantly improved survival rate. In addition, •OH and 1O2 destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of •OH, H2O2, 1O2, O2- was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.

A Review on Autism Spectrum Disorder Screening by Artificial Intelligence Methods.

PURPOSE: With the increasing prevalence of autism spectrum disorders (ASD), the importance of early screening and diagnosis has been subject to considerable discussion. Given the subtle differences between ASD children and typically developing children during the early stages of development, it is imperative to investigate the utilization of automatic recognition methods powered by artificial intelligence. We aim to summarize the research work on this topic and sort out the markers that can be used for identification. METHODS: We searched the papers published in the Web of Science, PubMed, Scopus, Medline, SpringerLink, Wiley Online Library, and EBSCO databases from 1st January 2013 to 13th November 2023, and 43 articles were included. RESULTS: These articles mainly divided recognition markers into five categories: gaze behaviors, facial expressions, motor movements, voice features, and task performance. Based on the above markers, the accuracy of artificial intelligence screening ranged from 62.13 to 100%, the sensitivity ranged from 69.67 to 100%, the specificity ranged from 54 to 100%. CONCLUSION: Therefore, artificial intelligence recognition holds promise as a tool for identifying children with ASD. However, it still needs to continually enhance the screening model and improve accuracy through multimodal screening, thereby facilitating timely intervention and treatment.

Association between extremely high prognostic nutritional index and all-cause mortality in patients with coronary artery disease: secondary analysis of a prospective cohort study in China.

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.

Influence of land use change on habitat quality: a case study of coal mining subsidence areas.

Revealing the spatiotemporal evolution characteristics and key driving processes behind the habitat quality is of great significance for the scientific management of production, living, and ecological spaces in resource-based cities, as well as for the efficient allocation of resources. Focusing on the largest coal-mining subsidence area in Jiangsu Province of China, this study examines the spatiotemporal evolution of land use intensity, morphology, and functionality across different time periods. It evaluates the habitat quality characteristics of the Pan'an Lake area by utilizing the InVEST model, spatial autocorrelation, and hotspot analysis techniques. Subsequently, by employing the GTWR model, it quantifies the influence of key factors, unveiling the spatially varying characteristics of their impact on habitat quality. The findings reveal a notable surge in construction activity within the Pan'an Lake area, indicative of pronounced human intervention. Concurrently, habitat degradation intensifies, alongside an expanding spatial heterogeneity in degradation levels. The worst habitat quality occurs during the periods of coal mining and large-scale urban construction. The escalation in land use intensity emerges as the primary catalyst for habitat quality decline in the Pan'an Lake area, with other factors exhibiting spatial variability in their effects and intensities across different stages.

The combined effects of ultrasound and plasma-activated water on silkworm pupae:Physicochemical properties, microbiological diversity and ultrastructure.

A novel technique was proposed for processing silkworm pupae by combining plasma- activated water (PAW) with ultrasound (US). The microbial diversity and quality characteristics of the silkworm pupae were also evaluated. The results of the microbial diversity analysis indicated that PAW combined with US treatment significantly reduced the relative abundance of Streptococcaceae, Leuconostocaceae, and Acetobacteraceae from 32%, 18% and 16% to 27%, 11% and 11%, respectively. Microstructural analysis demonstrated that the collapse of the internal structure of chitin in silkworm pupae facilitated the release of nutrients and flavour compounds including fatty acids, water-soluble proteins (WSP), amino acids, phenolics, and volatile compounds. Furthermore, the increase in antioxidant capacity and the decrease in catalase activity and malondialdehyde content confirmed the mechanism of quality change. These findings provide new insights into the possible mechanism of PAW combined with US to improve the quality of edible insects.