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Abstract Vascular endothelial cells are the predominant cell type in the cardiovascular system, and their dysfunction and death following hypoxic injury contribute to vascular lesions, playing an essential role in cardiovascular disease. Despite its importance, the mechanisms underlying vascular endothelial cell injury under hypoxia and potential therapeutic interventions remain poorly understood. Here, we constructed both an in vivo hypoxia model in C57BL/6 mice and an in vitro hypoxia model in HUVEC cells. Our findings demonstrated that hypoxia induces necroptosis in vascular endothelial cells and exacerbates inflammatory injury in vivo and in vitro, as evidenced by immunofluorescence and western blot. We identified FADD as a critical regulator of hypoxia-mediated necroptosis, with FADD knockdown significantly reversing hypoxia-induced necroptosis. Mechanistically, hypoxia affected protein conformation through SUMOylation of FADD and competitively inhibited its ubiquitination, leading to an increase in protein half-life and protein level of FADD. Furthermore, SUMOylation increased the interaction between FADD and RIPK1 and induced the formation of the FADD-RIPK1-RIPK3 complex, thereby promoting necroptosis in vascular endothelial cells. The SUMOylation inhibitor ginkgolic acid (GA) notably reduced hypoxia-induced vascular endothelial injury and inflammatory responses in male mice. Taken together, our research has uncovered a new process by which SUMOylation of FADD regulates hypoxia-induced necroptosis in endothelial cells, providing potential therapeutic targets for hypoxia-related cardiovascular diseases.

Some traditional building materials, such as concrete and steel, have a negative impact on the environment. With the in-depth implementation of sustainable development, green materials are gradually being considered, and bamboo is a green high-energy building material. However, there have been few studies on the prediction of mechanical properties of bamboo. In order to predict the longitudinal compressive properties of bamboo, tests were carried out on the longitudinal compressive tests of bamboo. The failure mode was explored, as well as the relationship between the physical and mechanical properties of bamboo. Prediction formulas were developed for the longitudinal compressive properties of bamboo. The results showed that the failure mode of the longitudinal compressive test of bamboo was ductile failure. The wall thickness and diameter of bamboo were found to be positively correlated with height. The longitudinal compressive strength and elastic modulus were positively correlated with height and negatively correlated with wall thickness and diameter. The longitudinal compressive strength and elastic modulus were positively correlated with height. The linear model can be used to fit the relationship between mechanical properties and height. This research provides a reference for the prediction of bamboo properties.

Abstract Background Calcium-dependent protein kinases (CDPKs) phosphorylate downstream target proteins in response to signals transmitted by free calcium ions (Ca2+, one of the second messengers) and thus play important regulatory roles in many biological processes, such as plant growth, development, and stress response. Results A bioinformatic analysis, as well as thorough evolutionary and expression investigations, were conducted to confirm previous reports of functional evidence for plant CDPKs. Using the Phytozome database’s BLAST search engine and the HMM search tool in TBtools software, we discovered that CDPKs are well conserved from green algae to flowering angiosperms in various gene family sizes. Additional investigations of the obtained CDPKs revealed high conservation of domain and motif numbers, gene architectures, and patterns. However, this conservation differed among plant species. Phylogenetic analysis demonstrated that the CDPK gene family diverged from a common ancient gene. Similarly, investigations into plant interspecies evolutionary relationships revealed common ancestral plant species, suggesting speciation of plants and evolution based on plant adaptation and diversification. A search for the driving force of CDPK gene family expansion revealed that dispersed duplication events, among other duplication events, contributed largely to CDPK gene family expansion. Gene localization analysis in P. trichocarpa demonstrated that most CDPK genes are localized within several cell organelles and bind other kinases and proteins to perform their biological functions efficiently. Using RNA-seq data and qPCR analyses, we postulated that PtCDPKs play functional roles in abiotic stress responses by regulating cold, heat, drought and salt stress to varying extents. Conclusion The CDPK genes are well conserved in plants and are critical entities in abiotic stress regulation, and further exploration and manipulation of these genes in the future may provide solutions to some of the challenges in agriculture, forestry and food security.

Abstract Renal fibrosis is a common outcome of chronic kidney diseases and glycolysis drives the development of renal fibrosis in damaged kidneys. Ulinastatin (UTI) is a broad-spectrum protease inhibitor with anti-inflammatory and antioxidant properties with anti-fibrosis effects. In this study, we aimed to verify whether UTI could exert anti-renal fibrosis effects by inhibiting glycolysis and explored the potential mechanisms. Renal fibrosis was induced in mice via unilateral ureteral obstruction (UUO). Transforming growth factor-β1 stimulates human kidney proximal tubular epithelial cells to undergo fibrotic changes. Histopathological staining was used to observe the pathological changes in the kidneys. The levels of fibrosis biomarkers, glycolytic enzymes, and key signaling molecules were determined using gene and protein assays. Cellular energy metabolism was measured using Seahorse XF24 analyzer. Modulated the activity of adenylate-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) to confirm that AMPK can regulate HIF-1α-mediated glycolysis. Furthermore, UTI and AMPK knockdown were combined to verify whether UTI could attenuate glycolysis via the AMPK pathway. UTI pretreatment improved UUO-induced renal injury and fibrosis. The expression of fibrosis biomarkers and glycolytic enzymes was reduced by UTI at both mRNA and protein levels. UTI treatment decreased the rate of glycolysis and the production of glycolytic intermediates in fibrotic cells and tissues. Furthermore, AMPK can regulate HIF-1α-mediated glycolysis in renal tubular epithelial cells. Finally, the attenuation of glycolysis by UTI was related to AMPK/HIF-1α pathway, and this effect was inhibited by knockdown AMPK. UTI can effectively alleviate renal fibrosis, which may be partly attributed to the reduction of glycolysis by regulating AMPK/HIF-1α pathway.

Abstract Data proliferation in the digital age necessitates robust encryption techniques to protect information privacy. Optical encryption leverages the multiple degrees of freedom inherent in light waves to encode information with parallel processing and enhanced security features. However, implementations of large-scale, high-security optical encryption have largely remained theoretical or limited to digital simulations due to hardware constraints, signal-to-noise ratio challenges, and precision fabrication of encoding elements. Here, we present an optical encryption platform utilizing scattering multiplexing ptychography, simultaneously enhancing security and throughput. Unlike optical encoders which rely on computer-generated randomness, our approach leverages the inherent complexity of light scattering as a natural unclonable function. This enables multi-dimensional encoding with superior randomness. Furthermore, the ptychographic configuration expands encryption throughput beyond hardware limitations through spatial multiplexing of different scatterer regions. We propose a hybrid decryption algorithm integrating model- and data-driven strategies, ensuring robust decryption against various sources of measurement noise and communication interference. We achieved optical encryption at a scale of ten-megapixel pixels with 1.23 µm resolution. Communication experiments validate the resilience of our decryption algorithm, yielding high-fidelity results even under extreme transmission conditions characterized by a 20% bit error rate. Our encryption platform offers a holistic solution for large-scale, high-security, and cost-effective cryptography.

Berberine (BBR) is a pentacyclic benzylisoquinoline alkaloid widely distributed across various medicinal plants. Recent studies have demonstrated that berberine possesses a broad spectrum of pharmacological activities, including not only antioxidant properties but also the ability to lower blood glucose, modulate lipid profiles, and mitigate inflammation. These findings suggest that berberine holds significant potential as a therapeutic agent for renal diseases, highlighting its substantial research value. Moreover, when administered orally, berberine has been shown to exhibit a wide therapeutic safety margin. Several studies have identified berberine’s renoprotective effects across a range of kidney disorders, including diabetic nephropathy, renal fibrosis, renal aging, kidney toxicity induced by chemotherapy and antibiotics. These properties underscore berberine’s evolving therapeutic potential for both acute kidney injury (AKI) and chronic kidney disease (CKD). In summary, the research discussed in this article provides a comprehensive overview of the renoprotective effects of BBR and elucidates the molecular mechanisms underlying its therapeutic potential in the treatment of various renal disease. Furthermore, the article underscores the significance of berberine as a promising therapeutic agent for the treatment of kidney disorders.

Abstract Current research efforts in polymer and nanotechnology applications are primarily focused on cargo delivery to enhance the therapeutic index, with limited attention being paid to self‐molecularly targeted nanoparticles, which may also exhibit significant therapeutic potential. Long‐term and anomalous lipid accumulation in the liver is a highly relevant factor contributing to liver diseases. However, the development of the reliable medications and their pharmacological mechanisms remain insufficient. Herein, a polyguanide nanoinhibitors (PGNI) depot is constructed by copolymerizing biguanide derivatives in different proportions onto prepolymers. The nanoinhibitors for their ability to ameliorate lipid accumulation in vitro and in vivo is screened, and subsequently demonstrated that covalently polymeric guanidine chains exhibit superior efficacy in ameliorating hepatic lipid accumulation via heterogeneous mechanisms compared to small‐molecule guanidine. It is found that PGNIs stabilize guanidine metabolism in the liver, preferably for biosafety. More importantly, PGNI is ingested and localized in hepatocyte lysosomes and is locked to interact with vesicular adenosine triphosphatase (V‐ATPase) on lysosomes, leading to the inhibition of V‐ATPase and lysosomal acidification, thereby activating the AMPK pathway, reducing fatty acid synthesis, and enhancing lipolysis and fatty acid oxidation. These results imply that polymer‐formed nanoparticles can serve as targeted inhibitors, offering a novel approach for therapeutic applications.

[Introduction] This paper aims to deeply analyze and improve China's carbon pricing mechanism to more effectively promote the social transition to green and low-carbon, and at the same time enhance China's leadership and initiative in the process of global carbon peaking and carbon neutrality. [Method] By comprehensively sorting out the current situation and future trends of the global carbon pricing mechanism, this article deeply analyzed the shortcomings of China's existing carbon pricing mechanism, such as insufficient correlation with the overall climate policy goals, unclear nature of property rights in the carbon market, and inactive market entities. This paper further discussed the potential impact of rising carbon price on China's emission reduction effect and energy supply guarantee. [Result] Based on China's national conditions, this paper gives the strategic direction and corresponding measures to construct China's carbon pricing mechanism by using carbon market carbon quota, carbon tax, coordination between carbon market and carbon tax, and carbon finance. [Conclusion] On the basis of clarifying the development ideas of China's carbon pricing mechanism, it provides a countermeasure reference for China to win more voice in the international carbon pricing mechanism, such as strategies for synergizing the domestic electricity certificate and carbon markets, improving the "integrity" of China's green certificates, engaging in the promotion of mutual recognition in international carbon markets, and collaborating to establish coordinated carbon pricing mechanisms among nations.

Abstract Background Liriodendron chinense is susceptible to extinction due to the increasing severity of abiotic stresses resulting from global climate change, consequently impacting its growth, development, and geographic distribution. However, the L. chinense remains pivotal in both socio-economic and ecological realms. The LRR-RLK (leucine-rich repeat receptor-like protein kinase) genes, constituting a substantial cluster of receptor-like kinases in plants, are crucial for plant growth and stress regulation and are unexplored in the L. chinense. Result 233 LchiLRR-RLK genes were discovered, unevenly distributed across 17 chromosomes and 24 contigs. Among these, 67 pairs of paralogous genes demonstrated gene linkages, facilitating the expansion of the LchiLRR-RLK gene family through tandem (35.82%) and segmental (64.18%) duplications. The synonymous and nonsynonymous ratios showed that the LchiLRR-RLK genes underwent a purifying or stabilizing selection during evolution. Investigations in the conserved domain and protein structures revealed that the LchiLRR-RLKs are highly conserved, carrying conserved protein kinase and leucine-rich repeat-like domians that promote clustering in different groups implicating gene evolutionary conservation. A deeper analysis of LchiLRR-RLK full protein sequences phylogeny showed 13 groups with a common ancestor protein. Interspecies gene collinearity showed more orthologous gene pairs between L. chinense and P. trichocarpa, suggesting various similar biological functions between the two plant species. Analysis of the functional roles of the LchiLRR-RLK genes using the qPCR demonstrated that they are involved in cold, heat, and salt stress regulation, especially, members of subgroups VIII, III, and Xa. Conclusion Conclusively, the LRR-RLK genes are conserved in L. chinense and function to regulate the temperature and salt stresses, and this research provides new insights into understanding LchiLRR-RLK genes and their regulatory effects in abiotic stresses.

Waterborne epoxy resin (WER) has excellent chemical stability, heat resistance, and mechanical properties, and its application in emulsified asphalt modification is receiving widespread attention in road maintenance. In this paper, the mechanical properties of waterborne epoxy resin modified emulsified asphalt (WEA) binder through different preparation processes were investigated, and the influence of WER on the microstructure, rheological properties, and low-temperature stability of emulsified asphalt was analyzed. The results show that WEA binders prepared using a two-step method can make the curing reaction of the modifier more complete and the mechanical properties more excellent. With the increase of modifier content, WER gradually formed a continuous skeleton structure in emulsified asphalt, and the critical content for the continuous phase of the system to transform from emulsified asphalt to WER was about 15 %. WER could undergo polymerization reactions in emulsified asphalt, and its modification process of emulsified asphalt was mainly physical modification. With the increase of modifier content, the linear viscoelasticity range of the WEA binder gradually decreased, and the high-temperature deformation resistance was significantly improved. The influence of loading frequency on rheological properties also gradually weakened. In addition, WER could significantly improve the high-temperature elastic recovery performance of emulsified asphalt. The elastic recovery rate of the WEA binder exceeded 98 % when the content of the modifier exceeded 15 %. However, WER had certain adverse effects on emulsified asphalt's low-temperature performance, so the modifiers' content should be strictly controlled.

The Sommerfeld effect is a phenomenon in which a non-ideal prime mover fails to provide enough energy around the resonance speed in a vibration system, resulting in resonance capture and a nonlinear jump. This study discusses the successful techniques for attenuating the Sommerfeld effect in a vibration system with four degrees of freedom (DOFs) driven by a non-ideal induction motor. The kinetic equations of the system are derived using the Lagrange function. Additionally, the mean rotational speed and stability of a non-ideal motor are studied by energy balance and perturbation analysis method. Then, the relationship between electromagnetic torque and motor speed in the Sommerfeld effect is analyzed. The Sommerfeld effect exists near the natural frequencies (NFs) with electrical frequency increased or decreased. The main reason is that the gradually increasing mechanical load power of the vibrating system near the NFs contradicts the finite electromagnetic output power of the non-ideal induction motor. Moreover, the validity of the proposed methods is demonstrated through numerical analysis and simulation. The Sommerfeld effect can be effectively mitigated by appropriately increasing the damping coefficient, reducing the installation distance, and minimizing both the eccentric mass and eccentricity radius of the rotor.

Highlights Analyze the primary causes of cathode failure in three representative batteries, illustrating their underlying regeneration mechanism. The latest research status of direct regeneration of spent lithium–ion batteries was reviewed and summarized in focus. The application examples of direct regeneration technology in production practice are introduced for the first time, and the problems exposed in the initial stage of industrialization were revealed.

Abstract Background The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. Methods We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. Results Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III–IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200–5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021–1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III–IV cardiac function (HR = 1.945, 95% CI: 1.149–3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845–0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429–0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025–4.554, p = 0.043) increased the mortality risk after six months of USPD. Conclusion Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III–IV cardiac function, WBC count, potassium, and calcium levels.

Systematic tests of longitudinal compression, bending, longitudinal shear, and longitudinal tensile strength of bamboo were conducted to study the variation of mechanical properties and the height-diameter ratio of bamboo. The predictive relations of mechanical properties and height-diameter ratio were fitted by linear regression analysis. The results showed that the mechanical properties of longitudinal compression, bending, longitudinal shear, and longitudinal tensile strength of bamboo increased with the increase of the height-diameter ratio. In this paper, the method of deducing the relationship between mechanical properties and height-diameter ratio of bamboo through the linear fitting relationship between mechanical properties and height-diameter ratio was shown to have high applicability and accuracy for bamboo. This paper has a certain reference value for the evaluation of mechanical properties of bamboo and has a certain practical value for reducing the testing cost.

Vertebrate neurons are highly dynamic cells that undergo several alterations in their functioning and physiologies in adaptation to various external stimuli. In particular, how these neurons respond to physical exercise has long been an area of active research. Studies of the vertebrate locomotor system's adaptability suggest multiple mechanisms are involved in the regulation of neuronal activity and properties during exercise. In this brief review, we highlight recent results and insights from the field with a focus on the following mechanisms: (a) alterations in neuronal excitability during acute exercise; (b) alterations in neuronal excitability after chronic exercise; (c) exercise-induced changes in neuronal membrane properties via modulation of ion channel activity; (d) exercise-enhanced dendritic plasticity; and (e) exercise-induced alterations in neuronal gene expression and protein synthesis. Our hope is to update the community with a cellular and molecular understanding of the recent mechanisms underlying the adaptability of the vertebrate locomotor system in response to both acute and chronic physical exercise.

Abstract We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P

The reinjection exploitation of hydrothermal resources is a recognized method of sustainable exploitation. The well space between the production and reinjection well is an essential issue because the thermal breakthrough in production well is the main negative impact during reinjection. The migration of reinjection water in the geothermal reservoir depends on the permeability of the reservoir, constrained by the geothermal reservoir characteristics. In this study, A numerical model using the Petrasim software with Tough2, as the core as well as reservoir data of each typical geothermal field in Jiyang depression, was established. The impact of the reservoir porosity and permeability and the thickness of a single sand layer on the migration of reinjection water and temperature field in the geothermal reservoir were analyzed systematically. The simulation results revealed that the reservoir porosity had a minor impact on the reinjection of the geothermal reservoir, including the reinjection pressure and the spacing of production and reinjection wells. The reservoir permeability affected the reinjection pressure, and then controlled the reinjection performance of the geothermal reservoir, while it had no impact on the spacing of production and reinjection wells. The sand layer superposition combination had a minor impact on the reinjection pressure of the geothermal reservoir. The distance of the horizontal migration of reinjection water in the multilayer stacked thin sand layers was longer, and the range of temperature influence was larger. Thus, it is necessary to expand the well space between production and reinjection well. This study is of significance for the stable operation of geothermal development projects.

Given the increasing importance of effectively identifying synergistic changes between PM2.5 and O3 and comprehensively analyzing their impact on air quality management in China, we employ the Sen+Mann–Kendall (Sen+M-K) trend test in this study to examine the temporal and spatial variation trends of PM2.5 and O3 in the Yangtze River Delta (YRD), from 2003 to 2020. We identified the regions where these pollutants exhibited synergistic changes and established the pathways between the pollutants and their potential drivers, using geographically weighted random forest algorithms and structural equation modeling. The study results revealed as follows: (1) Overall, the PM2.5 concentrations show a decreasing trend, while the O3 concentrations exhibit an increasing trend, in the YRD. Analysis of the combined trends indicates that approximately 95% of the area displays opposing trends for PM2.5 and O3, with only about 4% in the southern region showing synergistic trends for both pollutants. (2) Drought and the average temperature are the main drivers of the changes in PM2.5 and O3 concentrations in areas experiencing synergistic changes. Their combined effects alleviate the aggregation of PM2.5 and reduce the formation of VOCs, indirectly reducing the generation of pollutants. The negative effect of the average temperature on the O3 concentration may indicate the existence of nonlinear effects and complex interaction effects between the drivers. NOx and VOCs play important dual roles in the generation and conversion of pollutants, although their overall impact is smaller than meteorological factors. They produce significant indirect effects through their interaction with meteorological and other human factors, further affecting the concentrations of PM2.5 and O3. In areas without coordinated changes, the main impact of meteorological factors remains unchanged, and the relationship between the two anthropogenic emission sources and their effects on PM2.5 and O3 are complex, with different directions and levels involved. This study provides detailed insights into the drivers of air quality changes in the YRD and offers a scientific basis for environmental management authorities to develop more comprehensive and targeted strategies for balancing the control of PM2.5 and O3 pollution.

Objective: Proton magnetic resonance spectroscopy (1H-MRS) was applied in this study to detect metabolite changes in the brain of post-stroke cognitive impairment (PSCI) and normal volunteers. The levels of N-acetylaspartate (NAA) and creatinine (Cr) and in the frontal lobe, hippocampus and cingulate gyrus were measured to distinguish patients with post-stroke cognitive impairment (PSCI) and normal control group (NC). The relationship between them and cognitive function was explored and a critical value of the metabolite ratio was predicted. This study may serve as a reference for the diagnosis of cognitive dysfunction after stroke. Methods: A total of 46 patients with PSCI (PSCI group, all patients are unilateral cerebral infarction or intracerebral haemorrhage) were screened by the Mini-Mental Status Examination (MMSE), and 35 healthy volunteers were selected as normal control group (NC group). The general information of gender, age, and education level was matched between the two groups. Two groups of subjects were examined using MRS and evaluated for cognitive function using the MMSE test and the Montreal Cognitive Assessment Scale (MoCA). The correlation between MRS and neurobehavioral scale (MMSE test and MoCA scale) was analysed, and the possible demarcation points of the brain metabolism of PSCI were evaluated. Result: The MMSE and MoCA scores of patients with PSCI were lower significantly when compared with those of the NC group (P

Abstract Background Mitofusin 2 (MFN2) plays an important role in many tumors, but how its role in renal clear cell carcinoma needs further research. Methods In this study, we analyzed the expression of MFN2 in renal clear cell carcinoma tissues and normal kidney tissues through the Cancer Genome Atlas (TCGA) database and our clinical samples.Enrichment analysis was performed to determine MFN2-related pathways and biological functions. The correlation of MFN2 expression with immune cells was analyzed.The correlation of the expression of methylation and the methylation sites of MFN2 were analyzed by UALCAN and TCGA databases. Univariate / multivariate COX risk regression and Kaplan-Meier methods were used to determine the prognostic value of MFN2.Nomograms were drawn to predict overall survival (OS) at 1,3, and 5 years. We investigated the role of MFN2 in renal cancer cells using CCK 8, clone formation, wound healing assay, and methylase qPCR experiments. Results MFN2 is poorly expressed in renal clear cell carcinoma compared to normal kidney tissue,and is significantly negatively associated with TNM stage, histological grade and pathological stage.MFN2 was directly associated with OS after multivariate Cox regression analysis.MFN2 shows a hypomethylation state and shows a positive correlation with multiple methylation sites.Signaling pathways through functional enrichment to B-cell receptors and oxidative stress-induced senescence.Moreover, the low expression of MFN2 was positively correlated with the degree of immune cell infiltration in a variety of immune cells.In vitro experiments showed that overexpression of MFN2 significantly inhibited the proliferation and migration of renal clear cells and promoted methylation. Conclusions In conclusion, MFN2 can be used as a novel prognostic marker for renal clear cell carcinoma and requires further investigation of its role in tumor development.

BackgroundThis study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization.MethodsThis cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire.ResultsThis study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0–26) and 43.68 ± 6.01 (range: 21–50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000–5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2–3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2–3 months (OR = 3.342, P = 0.033) were independently associated with attitude.ConclusionCAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

Summary: Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0–1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

BackgroundThe morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function.MethodsGenome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3–5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses.ResultsThe increase of BWM exhibited a correlation with a reduction in eGFR (β = −0.02; P = 6.95 × 10−16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (β = −0.16; P = 5.91 × 10−36). For each standard deviation increase in BWM, the risk of CKD stages 3–5 increases by 32% (OR, 1.32; 95% CI, 1.19–1.47; P = 1.43 × 10−7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07–1.38; P = 0.002).ConclusionThe increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.

Abstract Background Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the timely prevention and treatment. Normally, fasting blood glucose (FBG) by physical examination is used for large-scale screening of DM; however, some people with normal fasting glucose (NFG) actually have suffered from diabetes but are missed by the examination. This study aimed to investigate whether common physical examination indexes for diabetes can be used to identify the diabetes individuals from the populations with NFG. Methods The physical examination data from over 60,000 individuals with NFG in three Chinese cohorts were used. The diabetes patients were defined by HbA1c ≥ 48 mmol/mol (6.5%). We constructed the models using multiple machine learning methods, including logistic regression, random forest, deep neural network, and support vector machine, and selected the optimal one on the validation set. A framework using permutation feature importance algorithm was devised to discover the personalized risk factors. Results The prediction model constructed by logistic regression achieved the best performance with an AUC, sensitivity, and specificity of 0.899, 85.0%, and 81.1% on the validation set and 0.872, 77.9%, and 81.0% on the test set, respectively. Following feature selection, the final classifier only requiring 13 features, named as DRING (diabetes risk of individuals with normal fasting glucose), exhibited reliable performance on two newly recruited independent datasets, with the AUC of 0.964 and 0.899, the balanced accuracy of 84.2% and 81.1%, the sensitivity of 100% and 76.2%, and the specificity of 68.3% and 86.0%, respectively. The feature importance ranking analysis revealed that BMI, age, sex, absolute lymphocyte count, and mean corpuscular volume are important factors for the risk stratification of diabetes. With a case, the framework for identifying personalized risk factors revealed FBG, age, and BMI as significant hazard factors that contribute to an increased incidence of diabetes. DRING webserver is available for ease of application ( http://www.cuilab.cn/dring ). Conclusions DRING was demonstrated to perform well on identifying the diabetes individuals among populations with NFG, which could aid in early diagnosis and interventions for those individuals who are most likely missed.

Abstract Background Duchenne muscular dystrophy (DMD) is a rare hereditary muscular disease. The role of eosinophils in DMD has not been clarified. This study aims to evaluate the association between peripheral blood eosinophil count and severity and prognosis of DMD. Methods A retrospective cohort study was performed for 145 DMD patients between January 2012 and December 2020. Clinical data of 150 healthy children were collected as a control group. Logistic regression and Cox regression analyses were used to explore the influences of eosinophil count on DMD severity and prognosis. Results Eosinophil count in DMD group was lower than the control group (Z = 2.163, P = 0.031). It was negatively correlated with Vignos scale score, Spearman correlation coefficient was p = 0.245, P = 0.040 (at admission), p = 0.137, P = 0.032 (at follow-up); was a protective factor for high Vignos scale score at admission [odds ratio (OR) = 0.038, 95%CI: 0.002–0.752, P = 0.032] and follow-up (OR = 0.033,95%CI: 0.001–0.121, P = 0.039). The Cox regression analysis indicated that elevated eosinophil count was correlated with better therapeutic efficacy for DMD patients [hazard ratio (HR) = 2.218, 95%CI: 1.154–3.924, P = 0.016]. Conclusion Eosinophil count in peripheral blood was correlated with the severity of DMD. It could indicate the therapeutic efficacy and prognosis of DMD patients to a certain extent. Eosinophils may be a potentially valuable biomarker or therapeutic target for DMD.

Abstract Background Shenkang injection has been used clinically to lower creatinine levels. This study explored the mechanism of Shenkang injection on protecting kidney function from hyperglycemia-mediated damage. Methods This study utilized a STreptoZotocin (STZ)-induced rat model of diabetes. In total, 60 rats were randomized into either the control group (n = 15) injected with vehicle or treatment group (n = 45) injected with STZ to induce hyperglycemia. Eight weeks after diabetes onset, diabetic rats were further randomized to receive different treatments for 4 consecutive weeks, including vehicle (diabetic nephropathy group, n = 15), Shenkang (n = 15), or Valsartan (n = 15). At 12 weeks, a series of urine and blood measures were examined and damage to the kidney tissue was examined using histology. Expression of nephrin and transforming growth factor-β1 (TGF-β1) were characterized using immunohistochemistry and Western blot. Results Compared to the control group, rats in the diabetic nephropathy group showed significant kidney damage demonstrated by high kidneyindex, high levels of urinary albumin, albumin/creatinine ratio (ACR), blood urea nitrogen as well as histological evidence. Shenkang injection significantly improved kidney function in the diabetic rats by decreasing kidney index, ACR, and serum creatinine. Shenkang treatment also mitigated kidney damage, improved nephrin expression, and decreased TGF-β1 expression in the kidneys. Conclusions Shenkang treatment protected renal function in diabetic rats by increasing nephrin expression, which protects diabetic rats from hyperglycemia-mediated kidney damage.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 μmol·L−1 Zn (Zn100), 100 μmol·L−1 Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal–nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

The impact of global warming is increasing and thus exacerbating environmental stresses that affect plant yield and distribution, including the Eriobotrya japonica Lindl (Loquat tree). Eriobotrya japonica, a member of the Rosaceae family, is valued not only for its nutritious fruit but also for its medicinal purposes, landscape uses, and other pharmacological benefits. Nonetheless, the productivity of Eriobotrya japonica has raised a lot of concern in the wake of adverse environmental conditions. Understanding the characteristics of the LRR-RLK gene family in loquat is crucial, as these genes play vital roles in plant stress responses. In this study, 283 LRR-RLK genes were identified in the genome of E. japonica that were randomly positioned on 17 chromosomes and 24 contigs. The 283 EjLRR-RLK proteins clustered into 21 classes and subclasses in the phylogenetic analysis based on domain and protein arrangements. Further explorations in the promoter regions of the EjLRR-RLK genes showed an abundance of cis-regulatory elements that functioned in growth and development, phytohormone, and biotic and abiotic responses. Most cis-elements were present in the biotic and abiotic responses suggesting that the EjLRR-RLK genes are invested in regulating both biotic and abiotic stresses. Additional investigations into the responses of EjLRR-RLK genes to abiotic stress using the RT-qPCR revealed that EjLRR-RLK genes respond to abiotic stress, especially heat and salt stresses. Particularly, EjapXI-1.6 and EjapI-2.5 exhibited constant upregulation in all stresses analyzed, indicating that these may take an active role in regulating abiotic stresses. Our findings suggest the pivotal functions of EjLRR-RLK genes although additional research is still required. This research aims to provide useful information relating to the characterization of EjLRR-RLK genes and their responses to environmental stresses, establishing a concrete base for the following research.

Plant growth, yield, and distribution are significantly impacted by abiotic stresses, affecting global ecosystems and forestry practices. However, plants have evolved complex adaptation mechanisms governed by numerous genes and transcription factors (TFs) to manage these stresses. Among these, bZIP (basic leucine zipper) is a crucial regulator orchestrating morphological adaptations. This review aims to elucidate the multifaceted roles of bZIP TFs in plant species. We discuss the morphological changes induced by stress stimuli and the pivotal functions of bZIP TFs in mediating these responses. While several publications have explored the mechanisms of bZIP TFs in response to abiotic stresses, this review delves into the intricate regulatory networks, summarizing alternative splicing and post-translational modifications, signaling networks interacting with bZIP TFs, and genetic engineering of bZIP TFs. By synthesizing current research, this review provides an updated discussion on bZIP interactions with other proteins to regulate stresses such as cold, heat, drought, and salt. Additionally, it offers avenues for future research and applications of bZIP TFs to improve abiotic stress resilience in plants through genetic engineering.

ObjectiveTo explore the electroencephalogram (EEG) and clinical characteristics of childhood bathing epilepsy.MethodsWe conducted a prospective summary of the clinical data from 10 children with bathing epilepsy who were admitted to Hunan Children’s Hospital from April 2019 to November 2023 and analyzed their EEGs and clinical characteristics.ResultsOur 10 patients included eight males and two females, with seizure-onset ages ranging from 4 months and 20 days to 14 months. Nine cases showed normal intellectual development, and one case manifested delayed development. The Video-EEG (VEEG) findings showed that nine cases exhibited normal background with no interictal epileptic discharge. The seizures were characterized by lip cyanosis, tachycardia or bradycardia, weakness, paleness, and loss of consciousness. Ictal EEG revealed rhythmic fast waves, spike waves, spike-slow waves, or slow and sharp-wave activity over the temporal region (eight cases) or the occipital and temporal regions (one case), finally evolving into a delta rhythm that lasted for 57–201 s. These children exhibited no seizures after discontinuing bathing and were not administered antiseizure medication. The interictal EEG of one case reflected mild slow background and focal interictal epileptic discharge; and her semiology was eyes gazing to right, with clonic movements of the right face and lips, lip cyanosis, bradycardia, and impaired consciousness. Ictal EEG showed spike–wave and spike-slow-wave rhythms over the left central, parietal, and temporal regions; these then spread to the left hemisphere, lasting for approximately 104 s. This patient did not exhibit bathing seizures after stopping her bathing but later experienced frequent spontaneous and drug-resistant seizures. The interictal EEG background slowed down, while focal epileptic discharge increased. Her intellectual development was significantly delayed, and a novel pathogenic mutation in the SMC1A gene, c.298+2T>C, was detected. She was diagnosed with developmental and epileptic encephalopathy.ConclusionA majority of children with bathing epilepsy in our study showed focal autonomic seizures accompanied by impaired consciousness. Stopping bathing could control the seizures and showed a good prognosis. A few infants manifested a poor prognosis, and we posit that bathing seizure rarely constitute the early manifestations of developmental and epileptic encephalopathy. VEEG findings and clinical features can also indicate the prognosis.

The space of production well plays a crucial role in the heat extraction performance of the Enhanced Geothermal System (EGS), which have the potential to meet the growing global energy demand as a reliable energy source. Nonetheless, there has been insufficient research and attention focused on comprehending the impact of the space of production well on the efficiency and effectiveness of EGS. In this work, a series of numerical simulations were conducted to assess the impact of the space of production well on heat extraction efficiency in EGS. Three different cases were considered: Case 50 with 50 m production well spacing, Case 100 with 100 m production well spacing, and Case 150 with 150 m production well spacing. At the X-Y plane and Y-Z plane, the simulation results indicated that there were slight differences in temperature variation among the Case 50, Case 100 and Case 150. And the cooling area decreasing as the spacing of production wells decreased. Moreover, the delivery of cooling water via the injection well and its subsequent distribution to various reference points lead to a decline in temperature at each point, albeit with varying degrees of variation. Besides, the established efficiency (ef) for Case 50 is smaller than the Case 100 and Case 150 during the last 15 years. These findings contribute valuable insights to the exploration and exploitation of EGS systems and can serve as a guide for further research in this field.

Abstract Objectives To evaluate the manufacturability, efficacy and safety of allogeneic CD19 chimeric antigen receptor double‐negative T cells (CD19‐CAR‐DNTs) as an off‐the‐shelf therapeutic cell product. Methods A membrane proteome array was used to assess the off‐target binding of CD19‐CAR. DNTs derived from healthy donors were transduced with lentiviral vectors encoding the CD19‐CAR. The manufacture of the CD19‐CAR‐DNTs was under GMP conditions, and their surface molecule expression patterns were characterised using flow cytometry. We investigated the off‐the‐shelf potential of CD19‐CAR‐DNTs by evaluating the cryopreserved CD19‐CAR‐DNTs in terms of cell viability as well as their cytotoxicity against various CD19+ target cell lines and primary patient blasts in vitro. We evaluated the persistence and safety of the cryopreserved CD19‐CAR‐DNTs in xenograft models in vivo. Results GMP‐grade CD19‐CAR‐DNTs were manufactured and cryopreserved for use in advance. The cryopreserved CD19‐CAR‐DNTs maintain their viability and antitumor activity against various CD19+ target cell lines and primary patient blasts. These cells significantly prolonged the survival in Raji‐Luc‐xenografted NOG mice. Multiple infusions of the cells can further augment their efficacy. Remarkably, following a single infusion in mice, CD19‐CAR‐DNTs rapidly got distributed among well‐perfused organs initially, and progressively spread to most tissues, peaking at Day 43. In toxicity studies, CD19‐CAR‐DNTs significantly reduced tumor burden and ameliorated tissue damage in tumor‐bearing NOG mice. Critically, no immunotoxicity or graft versus host disease was observed in non‐tumor‐bearing NOG mice. Conclusions The allogeneic CD19‐CAR‐DNTs fulfil the requirements of an off‐the‐shelf therapeutic cell product, offering a promising new approach to the treatment of haematological malignancies.