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Cardiovascular disease is a significant cause of death in humans. Various models are necessary for the study of cardiovascular diseases, but once cellular and animal models have some defects, such as insufficient fidelity. As a new technology, organoid has certain advantages and has been used in many applications in the study of cardiovascular diseases. This article aims to summarize the application of organoid platforms in cardiovascular diseases, including organoid construction schemes, modeling, and application of cardiovascular organoids. Advances in cardiovascular organoid research have provided many models for different cardiovascular diseases in a variety of areas, including myocardium, blood vessels, and valves. Physiological and pathological models of different diseases, drug research models, and methods for evaluating and promoting the maturation of different kinds of organ tissues are provided for various cardiovascular diseases, including cardiomyopathy, myocardial infarction, and atherosclerosis. This article provides a comprehensive overview of the latest research progress in cardiovascular organ tissues, including construction protocols for cardiovascular organoid tissues and their evaluation system, different types of disease models, and applications of cardiovascular organoid models in various studies. The problems and possible solutions in organoid development are summarized.

Abstract The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth’s magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

Abstract A high quality (Q) factor is essential for enhancing the performance of resonant nanoelectromechanical systems (NEMS). NEMS resonators based on two-dimensional (2D) materials such as molybdenum disulfide (MoS2) have high frequency tunability, large dynamic range, and high sensitivity, yet room-temperature Q factors are typically less than 1000. Here, we systematically investigate the effects of device size and surface nonidealities on Q factor by measuring 52 dry-transferred fully clamped circular MoS2 NEMS resonators with diameters ranging from 1 μm to 8 μm, and optimize the Q factor by combining these effects with the strain-modulated dissipation model. We find that Q factor first increases and then decreases with diameter, with an optimized room-temperature Q factor up to 3315 ± 115 for a 2-μm-diameter device. Through extensive characterization and analysis using Raman spectroscopy, atomic force microscopy, and scanning electron microscopy, we demonstrate that surface nonidealities such as wrinkles, residues, and bubbles are especially significant for decreasing Q factor, especially for larger suspended membranes, while resonators with flat and smooth surfaces typically have larger Q factors. To further optimize Q factors, we measure and model Q factor dependence on the gate voltage, showing that smaller DC and radio-frequency (RF) driving voltages always lead to a higher Q factor, consistent with the strain-modulated dissipation model. This optimization of the Q factor delineates a straightforward and promising pathway for designing high-Q 2D NEMS resonators for ultrasensitive transducers, efficient RF communications, and low-power memory and computing.

Abstract The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Abstract Background The utilization of live yeast (Saccharomyces cerevisiae, YE) in dairy cows is gaining traction in dairy production as a potential strategy to improve feed efficiency and milk yield. However, the effects of YE on dairy cow performance remain inconsistent across studies, leaving the underlying mechanisms unclear. Hence, the primary aim of this study was to investigate the impact of YE supplementation on lactation performance, ruminal microbiota composition and fermentation patterns, as well as serum antioxidant capacity and immune functions in dairy cows. Results Supplementation with YE (20 g/d/head) resulted in enhancements in dairy cow’s dry matter intake (DMI) (P = 0.016), as well as increased yields of milk (P = 0.002) and its components, including solids (P = 0.003), fat (P = 0.014), protein (P = 0.002), and lactose (P = 0.001) yields. The addition of YE led to significant increases in the concentrations of ammonia nitrogen (NH3-N) (P = 0.023), acetate (P = 0.005), propionate (P = 0.025), valerate (P = 0.003), and total volatile fatty acids (VFAs) (P

Pulmonary hypertension is a progressive disease of the pulmonary arteries that begins with increased pulmonary artery pressure, driven by progressive remodeling of the small pulmonary arteries, and ultimately leads to right heart failure and death. Vascular remodeling is the main pathological feature of pulmonary hypertension, but treatments for pulmonary hypertension are lacking. Determining the process of vascular proliferation and dysfunction may be a way to decipher the pathogenesis of pulmonary hypertension. In this review, we summarize the important pathways of pulmonary hypertension pathogenesis. We show how these processes are integrated and emphasize the benign role of aerobic exercise, which, as an adjunctive therapy, may be able to modify vascular remodeling in pulmonary hypertension.

With the increasing frequency of extreme rainfall events worldwide, urban flood in densely populated and economically vibrant urban areas has become a pressing issue drawing global attention. Catchments are fundamental units for understanding urban hydrological processes and managing flood. Current research often lacks an investigation into the importance and spatial differences of driving factors for urban flood at the catchment scale, particularly for different types of cities. This study uses 15 megacities in China as case studies and establishes a comprehensive system of driving factors. It categorizes cities based on population levels, climate zones, and spatial locations. The study begins with hotspot analysis to identify areas with high occurrences of urban inundation. Subsequently, it employs Geographic Weighted Regression (GWR), a spatial analysis technique, to unveil the mechanisms driving the spatial distribution of inundation points in different types of cities and the spatial heterogeneity of driving factors at the urban catchment scale. The research findings, based on multiple cities, demonstrate that urban inundation points exhibit clear spatial clustering characteristics. While impervious surfaces and urban buildings are generally more important than factors such as landscape patterns and population density, the importance and explanatory power of driving factors for the spatial distribution of urban inundation vary across different cities and even within different catchments of the same city. The categorization of cities based on population levels and spatial locations demonstrates stronger regularities in driving mechanisms compared to categorization based on climate zones. The study’s results further underscore the complex driving mechanisms behind the spatial distribution of urban inundation. This highlights the need for flood management strategies that consider both universal patterns of inundation occurrence and the specific characteristics of local driving factors to develop targeted and effective mitigation measures.

Abstract Optical detection of magnetic field is appealing for integrated photonics; however, the light-matter interaction is usually weak at low field. Here we observe that the photoluminescence (PL) decreases by > 40% at 10 mT in rubrene microcrystals (RMCs) prepared by a capillary-bridge assembly method. The giant magneto-PL (MPL) relies on the singlet-triplet conversion involving triplet-triplet pairs, through the processes of singlet fission (SF) and triplet fusion (TF) during radiative decay. Importantly, the size of RMCs is critical for maximizing MPL as it influences on the photophysical processes of spin state conversion. The SF/TF process is quantified by measuring the prompt/delayed PL with time-resolved spectroscopies, which shows that the geminate SF/TF associated with triplet-triplet pairs are responsible for the giant MPL. Furthermore, the RMC-based magnetometer is constructed on an optical chip, which takes advantages of remarkable low-field sensitivity over a broad range of frequencies, representing a prototype of emerging opto-spintronic molecular devices.

Abstract Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung’s development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Background and objectivesLactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease.Materials and methodsThis study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane’s Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods.ResultsBy employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study.ConclusionThis study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.

Abstract Flexible electronics has emerged as a continuously growing field of study. Two‐dimensional (2D) materials often act as conductors and electrodes in electronic devices, holding significant promise in the design of high‐performance, flexible electronics. Numerous studies have focused on harnessing the potential of these materials for the development of such devices. However, to date, the incorporation of 2D materials in flexible electronics has rarely been summarized or reviewed. Consequently, there is an urgent need to develop comprehensive reviews for rapid updates on this evolving landscape. This review covers progress in complex material architectures based on 2D materials, including interfaces, heterostructures, and 2D/polymer composites. Additionally, it explores flexible and wearable energy storage and conversion, display and touch technologies, and biomedical applications, together with integrated design solutions. Although the pursuit of high‐performance and high‐sensitivity instruments remains a primary objective, the integrated design of flexible electronics with 2D materials also warrants consideration. By combining multiple functionalities into a singular device, augmented by machine learning and algorithms, we can potentially surpass the performance of existing wearable technologies. Finally, we briefly discuss the future trajectory of this burgeoning field. This review discusses the recent advancements in flexible sensors made from 2D materials and their applications in integrated architecture and device design.

In the tumor microenvironment, transforming growth factor β (TGF-β) contributes to neutrophil development toward a pro-tumor phenotype; however, the molecular mechanism by which this occurs remains unclear. Therefore, we explored the role of TGF-β in N2 neutrophil polarization and the subsequent effect on oral leukoplakia/oral squamous cell carcinoma (OL/OSCC) cells. The TGF-β-stimulated N2 culture supernatant promoted the proliferation of OL/OSCC cells. Analysis of the N2 supernatant using a cytokine array revealed significantly upregulated expression of soluble forms of receptor for advanced glycation end products (RAGE). TGF-β was found to induce the expression of RAGE and matrix metalloproteinase 9 (MMP9) in neutrophils. Additionally, MMP9 treatment could cleave RAGE and promote its secretion by neutrophils, thereby promoting cancer cell proliferation. In an established mouse model of oral cancer using 4NQO, RAGE were found to be highly expressed. Importantly, neutralizing antibodies against RAGE significantly inhibited oral cancer progression in mice. Analysis of clinical data from the TCGA database revealed that RAGE and MMP9 are highly expressed in head and neck squamous cell carcinoma (HNSCC) and that RAGE expression is significantly positively correlated with neutrophil infiltration. In conclusion, our results indicate that TGF-β promotes N2 neutrophil polarization through upregulation of soluble RAGE (sRAGE) secretion, leading to OSCC cell proliferation. Our findings also suggest that the sRAGE formed during N2 polarization may be a potential therapeutic target in OL/OSCC.

Abstract Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer‐associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction‐dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS‐cGAMP‐STING signaling loop, leading to increased production of interferon‐β (IFNβ) by MSCs. IFNβ reversely enhances the type I IFN (IFN‐I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA‐I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN‐I signaling, HLA‐I expression, and NK tolerance in human tumor samples. Thus, the NK‐resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.

Abstract Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G‐protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14‐year follow‐up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt‐induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high‐salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14‐year follow‐up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06‐2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension.

Abstract Normoalbuminuria has recently been associated with increased cardiovascular risk, and vascular aging is proposed as the early manifestation of cardiovascular disease. Here, the authors aimed to examine the association of high‐normal albuminuria and vascular aging in a Chinese cohort. From our previously established cohort, 1942 participants with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 or urinary albumin‐creatinine ratio (UACR)

Summary: Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987–June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63–6.91]) and high-increasing groups (13.11 [6.30–27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02–2.62], 1.22 [1.19–1.26], and 4.29 [3.38–5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00–2.23]) and high-increasing groups (2.45 [1.22–4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08–1.42], 1.00 [1.00–1.01], and 1.21 [1.05–1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

In order to obtain topical and non-irritating anti-glaucoma drugs, novel semicarbazide-containing sulfonamide derivatives were designed and synthetized by sugar tail method in this study. The hydrophilic monosaccharides were expected to form interaction with the hydrophilic site of hCA II meanwhile the linker semicarbazides are used to further enhance water solubility, and more importantly, regulate the pH values of the target compounds in aqueous solution. First, all target compounds were synthesized and evaluated for their CA inhibitory activities. The results showed our target compounds demonstrated comparable activity to the positive control drug acetazolamide. The best derivative 11d exhibits an IC50 value of 14 nM for hCA II and 2086-fold selectivity over CA I. Subsequently, physicochemical properties study showed that the target compounds displayed very good water solubility (up to 3 %) and neutral pH value in solutions. Meanwhile, the artificial membrane permeability assay was performed to verify that the target compound could also pass through the membrane structure despite their strong water solubility. In the glaucomatous rabbit eye model, the applied topically representative compounds showed strongly lowered intraocular pressure (IOP), as 1 % or 2 % water solutions. Subsequent drug-like evaluation showed our target compounds possessed low hemolysis effect and low cytotoxicity toward human corneal epithelial cell line. Also, it was not found that these target compounds had significant inhibition of hERG and CYP. In addition, these novel analogs also displayed good liver microsomal metabolic stability and plasma stability. Finally, docking studies provided the rational binding modes of representative compounds in complex with hCA II. Taken together, these results suggested that compound 11d may be a promising hCA II inhibitor deserving further development.

Short-circuit impedance is an important economic and technical index to test the cost, efficiency and operation safety of transformers. Increasing the short-circuit impedance of the transformer can reduce the influence of the transformer fault current on the system. The short-circuit impedance of a general power transformer is 4~7%. When the short-circuit impedance is too small, the short-circuit current is too large, which will cause harm to electrical equipment. This paper proposes a method to adjust the short-circuit impedance by adding magnetic shunts of different thicknesses between the high and low voltage windings of the transformer. Compared with other methods, this method does not change the structure of the transformer core and winding, and is simple and efficient. In this paper, a three-dimensional simulation model of a single-phase multi-winding transformer is established by Altair Flux to study the influence of the thickness of magnetic shunts on the short-circuit impedance of a transformer. The feasibility of the proposed method is verified by comparing the simulation with the measured values. The magnetic shunt is also introduced into the three-phase transformer. The result shows that adding magnetic shunts of different thicknesses between the high and low voltage windings of the transformer will change the distribution and size of the leakage of the magnetic field. The short-circuit impedance increases significantly with the increase in the thickness of the magnetic shunt, but a certain number of magnetic shunts have minimal effects on the efficiency of the transformer.

Global imperatives call for reduced water consumption in homogeneous, intensive farming systems, where farmland landscape heterogeneity significantly impacts anthropogenic, ecological, and socioeconomic factors. However, the impact of this heterogeneity on crop water footprint (WF) remains uncertain. To address this, this study assessed the WF at the landscape scale across 616 subplots (1 × 1 km) in a representative county of North China Plain from 2013 to 2019, integrating green (WFgreen), blue (WFblue), and gray (WFgray) water footprints. Results showed that the winter wheat–summer maize double cropping pattern (WM) exhibited the highest WFgreen, WFblue, and WFgray. Over six years, most subplots saw significant reductions in WFgreen, WFblue, WFgray, and WF. At the landscape scale, diversification (compositional heterogeneity), fragmentation, and spatial distribution (configurational heterogeneity) were assessed using Shannon’s diversity index (SHDI), edge density (ED), and effective mesh size (MESH), which exhibited average variations of 0.07, −3.16 m ha−1, and −5.86 m2, respectively. For WM patches, the percentage of landscape (PLAND) and MESH were used to evaluate diversification and spatial distribution, resulting in reductions of 1.14% and 2.32 m2, respectively. Regression analysis and structural equation modeling further illuminated the connections between the landscape pattern and WF, emphasizing the significant role of MESH in reducing WFblue and influencing crop diversity (p < 0.001). Therefore, spatial distribution, whether directly or through the mediation of diversification, demonstrated a more substantial overall impact on WF. Consequently, future research should prioritize investigating how spatial distribution influences crop choice and agronomic management in order to determine the optimal cropping patterns and field size that strike a balance between crop production and the water footprint. This study offers theoretical guidance and a scientific foundation for redesigning farmland landscapes to bolster water sustainability in intensive farming systems.

Abstract Background Lipid management with a low-density lipoprotein cholesterol (LDL-C) goal of

Abstract The transcriptional repressor Snail induces EMT during embryonic development and tumor metastasis. Growing evidence indicates that Snail functions as a trans-activator to induce gene expression; however, the underlying mechanism remains elusive. Here, we report that Snail cooperates with GATA zinc finger protein p66β to transactivate genes in breast cancer cells. Biologically, depletion of p66β reduces cell migration and lung metastasis in BALB/c mice. Mechanistically, Snail interacts with p66β and cooperatively induces gene transcription. Notably, a group of genes induced by Snail harbor conserved G-rich cis-elements (5′-GGGAGG-3′, designated as G-box) in their proximal promoter regions. Snail directly binds to G-box via its zinc fingers and transactivates the G-box-containing promoters. p66β enhances Snail binding affinity to G-box, whereas depletion of p66β results in a decreased binding affinity of Snail to the endogenous promoters and concomitantly reduces the transcription of Snail-induced genes. Taken together, these data demonstrated that p66β is critical for Snail-mediated cell migration by acting as a co-activator of Snail to induce genes containing G-box elements in the promoters.

BackgroundAcute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults.MethodsPubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17.ResultsTwelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration ConclusionsVitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries.Trial registrationThis study was registered on PROSPERO (CRD42023451265).

Mechanosensitive ion channels are a class of membrane-integrated proteins that convert externalmechanical forces, including stretching, pressure, gravity, and osmotic pressure changes, some of which can be caused by pathogen invasion, into electrical and chemical signals transmitted to the cytoplasm. In recent years, with the identification of many of these channels, their roles in the initiation and progression of many diseases have been gradually revealed. Multiple studies have shown that mechanosensitive ion channels regulate the proliferation, activation, and inflammatory responses of immune cells by being expressed on the surface of immune cells and further responding to mechanical forces. Nonetheless, further clarification is required regarding the signaling pathways of immune-cell pattern-recognition receptors and on the impact of microenvironmental changes and mechanical forces on immune cells. This review summarizes the roles of mechanosensitive ion channels in immune cells.

Abstract Background The new visceral adiposity index (NVAI) was superior to previous obesity indices in predicting cardiovascular diseases among Asians. Nevertheless, the utility of the NVAI for predicting chronic kidney disease is still unclear. The objective of this research was to explore the relationship between the NVAI and subclinical renal damage (SRD) and to investigate whether the NVAI outperforms other common obesity indices in predicting SRD in the Chinese population. Methods Participants in this cross-sectional study were from the Hanzhong Adolescent Hypertension Cohort. The NVAI and seven other common obesity indices were calculated, including body mass index, waist circumference, lipid accumulation product, visceral adiposity index, Chinese visceral adiposity index, a body shape index and metabolic score for visceral fat. Logistic regression models revealed the association between NVAI and SRD. The odds ratio (OR) and the 95% confidence interval (CI) were calculated to show the association between the two variables. The predictive power of eight obesity indices for SRD was evaluated through the receiver operating characteristic curve and area under the curve (AUC). In addition, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were also applied to compare the incremental predictive value for SRD of different obesity indices. Results The median age of the 2358 subjects was 42.00 years. Across NVAI tertiles, the prevalence of SRD was 7.25%, 11.21%, and 21.60%, respectively. After adjusting for confounders, a high level of NVAI remained a risk factor for SRD. The ORs of the middle and top NVAI tertiles for SRD were 1.920 (95% CI: 1.322, 2.787) and 4.129 (95% CI: 2.750, 6.202), respectively. The AUC of the NVAI was 0.666 (95% CI: 0.647, 0.685), which was significantly larger than the AUC of any of the other obesity indicators. Moreover, the NRI and IDI were significantly improved when NVAI was added to the basic model for predicting SRD. Among eight obesity indices, NVAI had the highest NRI (0.392; 95% CI: 0.280, 0.503), and its IDI (0.021; 95% CI: 0.014, 0.027) was second only to that of the body mass index (0.023; 95% CI: 0.014, 0.032). Conclusions NVAI is independently and positively associated with SRD. Among the eight obesity indices, the NVAI shows the strongest predictive power for SRD in the Chinese population. The NVAI may be useful as an effective warning indicator of chronic kidney disease in Chinese adults.

Abstract Hydrogen (H2) is currently of strategic importance in the pursuit of a decarbonized, environmentally benign, sustainable global energy system; however, the explosive nature of H2 requires leakage monitoring to ensure safe application in industry. Therefore, H2 gas sensors with a high sensitivity and fast response across a wide concentration range are crucial yet technically challenging. In this work, we demonstrate a new type of MEMS differential thermopile gas sensor for the highly sensitive, rapid detection of trace H2 gas in air. Facilitated by a unique MIS fabrication technique, pairs of single-crystalline silicon thermopiles (i.e., sensing and reference thermopiles) are batch fabricated with high-density single-crystalline silicon thermocouples, yielding an outstanding temperature sensitivity at the sub-mK level. Such devices ensure the detection of miniscule temperature changes due to the catalytic reaction of H2 with a detection limit as low as ~1 ppm at an operating temperature of 120 °C. The MEMS differential thermopiles also exhibit a wide linear detection range (1 ppm-2%, more than four orders of magnitude) and fast response and recovery times of 1.9 s and 1.4 s, respectively, when detecting 0.1% H2 in air. Moreover, the sensors show good selectivity against common combustible gases and volatile organics, good repeatability, and long-term stability. The proposed MEMS thermopile H2 sensors hold promise for the trace detection and early warning of H2 leakage in a wide range of applications.

Lubricants must exhibit good tribological behavior at low temperatures to ensure reliable startups in very cold regions. This study investigates the performance of lubricants, with a specific focus on their capacity for high-temperature lubrication and ensuring reliable low-temperature startup in engines. Experiments were conducted to assess the friction and wear characteristics of polydiethylsiloxane in conjunction with a Si3N4 ball and M50 (8Cr4Mo4V) steel across a temperature range of −80 °C to 25 °C. The results indicate that the coefficient of friction, as determined through friction and wear tests at various temperatures, remained below 0.1. As temperatures progressively decreased, the system’s friction coefficient increased, and wear volumes recorded at 25 °C and −60 °C were 9749.513 µm³ and 105.006 µm³, respectively, culminating in lubrication failure at −100 °C. This failure is primarily attributed to the increased viscosity and decreased mobility of polydiethylsiloxane at extremely low temperatures. Additionally, the reduced temperature increases the strength of the quenched steel, leading to hard particles or protrusions on the material’s surface, which collide with the Si3N4 ball during friction, causing adhesion and spalling. Despite this, polydiethylsiloxane forms a stable protective oil film on the surface, enhancing the system’s lubrication performance. However, below −80 °C, this oil film begins to tear, leading to diminished lubrication efficacy. This study provides valuable data supporting the field of cryogenic lubrication.

Porous tungsten gradient materials with ordered gradient variations in pore size have significant application value in the field of vacuum electronic devices. This work combines tape casting and dealloying methods to achieve the integrated preparation of porous tungsten gradient materials with a wide range of controllable porosity. The study focused on the phase composition and microstructure evolution during the preparation of porous tungsten gradient materials. The results show that the tape casting process allows for the precise and controllable thickness of each layer of the porous tungsten materials and uniform composition structure, while the stepwise dealloying of Fe and Ti enables a wide range of controllable porosity for the porous tungsten gradient materials. PVB, after thermal decomposition, provides a carbon source for the in situ reaction to form W-Fe-C compounds, and the surface diffusion behavior of W-Fe-C compounds at high temperatures improves the stratification of the porous tungsten gradient materials. This work provides a design concept for the integrated preparation of porous metal gradient materials.

Micromechanical resonators have aroused growing interest as biological and chemical sensors, and microcantilever beams are the main research focus. Recently, a resonant microcantilever with an integrated heater has been applied in on-chip thermogravimetric analysis (TGA). However, there is a strong relationship between the mass sensitivity of a resonant microcantilever and the location of adsorbed masses. Different sampling positions will cause sensitivity differences, which will result in an inaccurate calculation of mass change. Herein, an integrated H-shaped resonant beam with uniform mass sensitivity and temperature distribution is proposed and developed to improve the accuracy of bio/chemical sensing and TGA applications. Experiments verified that the presented resonant beam possesses much better uniformity of sensitivity and temperature distribution compared with resonant microcantilevers. Gas-sensing and TGA experiments utilizing the integrated resonant beam were also carried out and exhibited good measurement accuracy.

Natural killer (NK) cells kill mutant cells through death receptors and cytotoxic granules, playing an essential role in controlling cancer progression. However, in the tumor microenvironment (TME), NK cells frequently exhibit an exhausted status, which impairs their immunosurveillance function and contributes to tumor immune evasion. Emerging studies are ongoing to reveal the properties and mechanisms of NK cell exhaustion in the TME. In this review, we will briefly introduce the maturation, localization, homeostasis, and cytotoxicity of NK cells. We will then summarize the current understanding of the main mechanisms underlying NK cell exhaustion in the TME in four aspects: dysregulation of inhibitory and activating signaling, tumor cell-derived factors, immunosuppressive cells, and metabolism and exhaustion. We will also discuss the therapeutic approaches currently being developed to reverse NK cell exhaustion and enhance NK cell cytotoxicity in the TME.

Summary: Cancer is a major health threat and a leading cause of human death worldwide. Surgical resection is the primary treatment for most cancers; however, some patients develop locoregional recurrence. Here, we developed an in situ cancer therapeutic system aimed to locally treat cancer and prevent postoperative recurrence. A functional scaffold, based on alginate/gelatin and crosslinked with copper ions, was fabricated by 3D printing and showed an excellent photothermal effect under near-infrared (NIR) irradiation. The combination of copper ions and NIR effectively killed thyroid cancer cells and patient-derived organoids, indicating a synergetic and broad-spectrum antitumor effect on thyroid cancer through the chemo-photothermal therapy. This implantable stent is designed to provide effective treatment in the vicinity of the tumor site and can be degraded without secondary surgery. The copper-loaded hydrogel scaffold may be a potential candidate for local cancer treatment and pave the way for precise and effective cancer therapy.

IntroductionHeat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them.MethodsThus, at 28 days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28–42 days, the HS was kept at 31 ± 1°C (9:00–17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance (n = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment.Results and discussionThe results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of p

Background and aimsObesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage.MethodsA total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage.ResultsLAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI.ConclusionLAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.

Currently, the offline manual periodic detection method is a well-established practice in detecting the thermal state of the converter heatsink. This method, however, is huge in maintenance costs. To lower maintenance costs and improve maintenance efficiency in detecting the thermal dissipation state, this paper proposes an intelligent online prediction scheme based on Gauss-Newton iteration method. Firstly, the power loss model of the power module is established according to the characteristics of IGBT and FWD. The power loss of the power device is then calculated in real time with the voltage and current parameters of the converter. Next, the transient thermal model of the heatsink is established based on thermodynamics theory. And the calculation method of steady thermal resistance of heatsink based on Gauss-Newton iteration method is proposed according to the model. The transient thermal impedance data allow for timely prediction of thermal resistance of the heatsink and characterize the thermal state of the heatsink. Finally, with the help of DSP28377D, an experimental platform is built to verify the scheme. Results show that this method can realize intelligent prediction of thermal state online.

Abstract Backgrounds Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. Methods Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. Results We established 9 patient-derived PTC organoid models, 5 of which harbor BRAFV600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAFV600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAFV600E-mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. Conclusions These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

Bamboo plants are fast-growing, quickly produce usable material, and are an abundant resource. Bamboo is an excellent, natural, and renewable material. It has a long history of application in human life, industrial manufacturing, cultural industries, and other fields. The warehousing of bamboo and its finished products is an emerging industry with much potential. A reasonable, stable, and orderly warehouse could be an effective solution for the sustainable management, seasonal harvesting, and raw material stability issues. In addition, the warehouse plays an important role in the processing of raw materials, reserve logistics, keeping a robust and real-time supply for downstream products. This is of great significance for alleviating problems associated with Chinese timber safety and for improving the quality of life. This paper focuses on warehousing experience in grain and coal fields, reviews the common material processing and preservation measures of bamboo, analyzes advantages and developmental prospects of bamboo warehousing, and explores and suggests appropriate storage methods, technical systems, and application models. It is expected to provide technical guidance for construction in the bamboo storage industry, and to supply ideas and suggestions for the modern development of the bamboo industry.

Abstract Neural precursor cell expressed developmentally downregulated 4‐like (NEDD4L), a member of the E3 ubiquitin‐protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt‐sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt‐Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7‐day low‐salt diet (3.0 g/day) and a 7‐day high‐salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low‐salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high‐salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow‐up. SNP rs292449 was significantly associated with hypertension incidence over the 14‐year follow‐up. Finally, this gene‐based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14‐year follow‐up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.

Aqueous battery (AB) with non-metallic charging carriers is a viable candidate for grid energy storage devices owing to its comparatively low cost and high safety. However, developing practical electrode materials with remarkable electrochemical performance remains a great challenge. In this study, tungsten trioxide nanosheets (WONSs) with one-dimensional tunnels were facilely synthesized through a hydrothermal reaction. When used as the cathode material in aqueous batteries, the as-prepared WONS exhibits excellent long-term cycling stability and impressively high rate capability due to the nearly zero-strain structural characteristics of super-fast proton storage. Notably, a stable cycling performance with 89% capacity retention after 10000 cycles was achieved with an increased mass loading of WONS at around 12 mg cm−2. Our work points to a new direction of promoting high-efficiency AB applications with protons as charge carriers in a mild electrolyte.

Energy spectroscopy is a powerful tool with diverse applications across various disciplines. Variational quantum-classical algorithms based on programmable digital quantum simulators have emerged as promising approaches for conducting spectroscopy on various models using a single device, despite facing significant quantum and classical resource overheads. Here, we experimentally demonstrate multilevel variational spectroscopy for fundamental many-body Hamiltonians using a superconducting digital quantum simulator. By exploiting symmetries and the subspace search method, we achieve full spectroscopy for a four-qubit Heisenberg spin chain, yielding an average energy deviation as small as 0.13 from the theoretical values, assuming unity coupling strength. Our method, when extended to eight-qubit Heisenberg and transverse-field Ising Hamiltonians, successfully determines the three lowest-energy levels. In achieving the above, we introduce a circuit-agnostic compilation method that enhances the robustness of our simulator against signal crosstalk. Our study highlights the combination of the subspace search method and symmetry-assisted resource efficiency in variational quantum algorithms and lays the foundation for practical spectroscopy on near-term quantum simulators, with potential applications in quantum chemistry and condensed matter physics.

Abstract Background Nitrogen (N) is a major element and fundamental constituent of grain yield. N fertilizer plays an essential role in the roots, shoots, and leaves of crop plants. Here, we obtained two N-sensitive potato cultivars. Results The plants were cultivated in the pots using N-deficient and N-sufficient conditions. Crop height, leaf chlorophyll content, dry matter, and N-accumulation significantly decreased under N-deficient conditions. Furthermore, we performed a comprehensive analysis of the phenotype and transcriptome, GO terms, and KEGG pathways. We used WGCNA of co-expressed genes, and 116 differentially expressed hub genes involved in photosynthesis, nitrogen metabolism, and secondary metabolites to generate 23 modules. Among those modules, six NRT gene families, four pigment genes, two auxin-related genes, and two energy-related genes were selected for qRT-PCR validation. Conclusions Overall, our study demonstrates the co-expressed genes and potential pathways associated with N transport and accumulation in potato cultivars’ roots, shoots, and leaves under N-deficient conditions. Therefore, this study provides new ideas to conduct further research on improving nitrogen use efficiency in potatoes.

Many studies have been undertaken to predict local scour around offshore high-rise structure foundations (HRSFs), which have been used in constructing the Donghai Wind Farm in China. However, there have been few works on the turbulent flow that drives the scour process. In this study, the characteristics of the turbulent flow fields around an HRSF were investigated using the particle image velocimetry technique. The mean flow, vorticity, and turbulence intensity were analyzed in detail. The relationship between the flow feature and scour development around an HRSF was elaborated. The results showed that the flow velocity increased to its maximum value near the third row of the pile group. The shear layer and wake vortices could not be fully developed downstream of the last row of the piles at small Reynolds numbers. The strong flow and turbulent fluctuation near the third piles explained the existence of a long-tail scour pattern starting from the HRSF shoulders and a trapezoidal deposition region directly downstream of HRSF. This laboratory experiment gains insight into the mechanism of the turbulent flow around HRSFs and provides a rare dataset for numerical model verifications.

A schematic model of SGSM2 suppressing the progression of RASWT thyroid cancer.

Abstract Background The triglyceride-glucose index (TyG index) has emerged as a reliable surrogate marker of insulin resistance associated with arterial stiffness. However, most studies were based on a cross-sectional design, and few studies have evaluated the longitudinal impact of the TyG index on arterial stiffness. This study aimed to investigate the associations of single time point measurement and the long-term trajectory of the TyG index with arterial stiffness in a Chinese cohort. Methods Data are derived from the Hanzhong Adolescent Hypertension Cohort study. A total of 2480 individuals who participated in the 2017 survey was included in the cross-sectional analysis. A sample of 180 individuals from the sub-cohort with follow-up data in 2005, 2013, and 2017 was enrolled in the longitudinal analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2), and arterial stiffness was determined using brachial-ankle pulse wave velocity (baPWV). The latent class growth mixture modeling method was used to identify the TyG index trajectories from 2005 to 2017. Results In the cross-sectional analysis, the median age of the study population was 42.8 (39.8, 44.9) years, and 1351 (54.5%) were males. Each one-unit increment in TyG index was associated with a 37.1 cm/s increase (95% confidence interval [CI] 23.7–50.6 cm/s; P

Orthogonal modes are utilized to broaden the bandwidth of the communication systems and mode-order converter is a pivotal components component for mode-division-multiplexing systems. To provide an alternative solution which is both robust to the wavelength variation and has an ultracompact footprint, we propose a new concept of mode converter in this paper. We design two kinds of prototypes in which Sb2S3 are put above the silicon waveguides and embedded into the waveguides. The footprints of these devices are 2.21 μm × 7.06 μm and 1.04 μm × 2.73 μm, respectively. The cascaded gap can be compressed to 0.2 μm almost no additional loss is introduced. The simulation result shows that the insertion losses of device are lower than 1.9 dB and 1.3 dB, and the signal-to-noise ratios are larger than 11.2 dB and 10.1 dB throughout the wavelength of 1500–1600 nm. Moreover, the method to tune the mode-orders could also be applied to a series of dynamic devices utilizing modes.

Conventional techniques for in vitro cancer drug screening require labor-intensive formalin fixation, paraffin embedding, and dye staining of tumor tissues at fixed endpoints. This way of assessment discards the valuable pharmacodynamic information in live cells over time. Here, we found endogenous lipofuscin-like autofluorescence acutely accumulated in the cell death process. Its unique red autofluorescence could report the apoptosis without labeling and continuously monitor the treatment responses in 3D tumor-culture models. Lifetime imaging of lipofuscin-like red autofluorescence could further distinguish necrosis from apoptosis of cells. Moreover, this endogenous fluorescent marker could visualize the apoptosis in live zebrafish embryos during development. Overall, this study validates that lipofuscin-like autofluorophore is a generic cell death marker. Its characteristic autofluorescence could label-free predict the efficacy of anti-cancer drugs in organoids or animal models.

The morbidity and mortality of cardiovascular diseases are exceedingly high worldwide. Pathological heart remodeling, which is developed as a result of mitochondrial dysfunction, could ultimately drive heart failure. More recent research target exercise modulation of mitochondrial dysfunction to improve heart failure. Therefore, finding practical treatment goals and exercise programs to improve cardiovascular disease is instrumental. Better treatment options are available with the recent development of exercise and drug therapy. This paper summarizes pathological states of abnormal mitochondrial function and intervention strategies for exercise therapy.

ABSTRACT: The effect of compound probiotics on the caecum of broilers under heat stress was assessed in this study. A total of 400 twenty-eight-day-old AA male broilers were randomly divided into 4 treatment groups, where each group had 5 replicates of 20 broilers. The 4 treatment groups were a heat stress control group (broilers receiving a normal diet) and groups HP I, HP II, and HP Ⅲ, consisting of broilers receiving 1, 5, and 10 g of compound probiotics added to each kilogram of feed, respectively. Compound probiotics (L. casei, L. acidophilus, and B. lactis at a ratio of 1:1:2) were used to formulate a compound probiotic powder, with 1 × 1010 CFU/g of effective viable bacteria. Heat stress treatment was performed at 32 ± 1°C from 9:00 to 17:00 every day from 28 d to 42 d. In d 28 to 42, compared with the HC group, the ADG of broilers in the HP II and III groups was significantly increased (P < 0.05); the ADFI difference between groups was not significant (P > 0.05); the FCR of HP II and III broilers was significantly decreased (P < 0.05); and the FCR of the HP I group increased, but the difference was not significant (P > 0.05). Transcriptome results demonstrate that 665 differential genes were screened (DEGs; upregulated: 366, downregulated: 299). The DEGs were enriched in the B cell receptor signaling pathway, the intestinal immune network for IgA synthesis, the Fc epsilon RI signaling pathway, and other signaling pathways, according to KEGG enrichment analysis. Metabolome analysis identified 92 differential metabolites (DAMs; upregulated: 48, downregulated: 44). KEGG enrichment analysis indicated significant enrichment of Pantothenate and CoA biosynthesis and beta-Alanine metabolism. The combined transcriptome and metabolome analysis revealed that the DAMs and DEGs were mostly involved in beta-alanine metabolism, arginine biosynthesis, amino sugar and nucleotide sugar, and alanine, aspartate, and glutamate metabolism. The results of this study suggest that the addition of compound probiotics has a positive effect on intestinal metabolites, improving the growth performance and contributing to the overall health of broilers under heat stress.

Abstract Corin, a transmembrane serine protease that can cleave pro‐atrial natriuretic peptide (Pro‐ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt‐Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7‐day low salt diet (3 g/day) and a 7‐day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low‐salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low‐salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high‐salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow‐up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene‐based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8‐year follow‐up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.

Abstract Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.