Physical fitness decline and career paths: a longitudinal study of medical undergraduates.

INTRODUCTION: Exercise enhances one's health and competitiveness. A strong physical fitness status can pave the way for a promising future. This study presents the time-based trends in physical fitness indicators-including height, weight, BMI, lung capacity, dash, long-distance running, and standing long jump-among medical undergraduates during their university years. Additionally, we analyzed the impact of students' physical fitness on their career paths. METHOD: We conducted a retrospective database study by collecting physical fitness test data and career paths information for 634 medical students from a university in southwestern China. These students graduated in 2022. The career paths included pursuits in further studies, employment, and unemployment. To detect differences in these aspects, we used the t-test and Chi-square test. RESULTS: Our study indicates a significant declining trend in the physical fitness of medical students during their university years. The changes observed between the first and fourth tests are as follows: Weight (kg): 58.52 ± 10.48 to 60.73 ± 12.07, P < 0.00 BMI (kg/m^2): 20.79 ± 2.74 to 21.24 ± 3.06, P < 0.00 50-m dash (s): 8.91 ± 0.99 to 9.25 ± 1.11, P < 0.00 Standing long jump (cm): 187.74 ± 30.98 to 182.59 ± 32.25, P < 0.00 800-m run for females (min): 3.84 ± 0.47 to 4.48 ± 0.85, P < 0.00 1000-m run for males (min): 3.98 ± 0.63 to 4.62 ± 0.87, P < 0.00 Sit-ups for females (count): 30.39 ± 7.5 to 29.03 ± 8.82, P < 0.00 Upon analyzing the correlation between changes in physical fitness and career paths, students with stable or decreased BMI had better post-graduation outcomes compared to students with increased BMI. CONCLUSIONS: Medical students show a declining trend in physical fitness during their undergraduate years. A good physical health status is beneficial for achieving better career paths. Medical students should place greater emphasis on physical exercise during their time in school.

Regulatory effects of stress release from decellularized periosteum on proliferation, migration, and osteogenic differentiation of periosteum-derived cells.

Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin ß1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.

LIM homeobox 8 reduced apoptosis and promoted periodontal tissue regeneration function of dental pulp stem cells.

Stem cell-mediated tissue regeneration is a promising strategy for repairing tissue defects and functional reconstruction in periodontitis, a common disease that leads to the loss of alveolar bone and teeth. However, stem cell apoptosis, widely observed during tissue regeneration, impairs its efficiency. Therefore, the regulation of stem cell apoptosis is critical for improving regeneration efficiency. The LIM homeobox 8 gene LHX8, belongs to the LIM homeobox family, which was involved in tooth morphogenesis. Here, we found that LHX8 was significantly expressed in dental pulp. LHX8 knockdown significantly increased dental pulp mesenchymal stem cells (DPSCs) apoptosis, as confirmed by RT-PCR, western blotting, flow cytometry, and transmission electron microscopy. Additionally, LHX8 overexpression inhibited apoptosis and enhanced the osteo/odontogenic differentiation potential of hDPSCs in vitro. Furthermore, LHX8-overexpression could enhance the periodontal tissue regeneration efficiency of hDPSCs in mice with periodontitis. In conclusion, the present study indicates that LHX8 inhibits stem cell apoptosis and promotes functional tissue formation in stem cell-based tissue regeneration engineering, suggesting a new therapeutic target to increase the efficacy of periodontal tissue regeneration.

Plant height as an indicator for alpine carbon sequestration and ecosystem response to warming.

Growing evidence indicates that plant community structure and traits have changed under climate warming, especially in cold or high-elevation regions. However, the impact of these warming-induced changes on ecosystem carbon sequestration remains unclear. Using a warming experiment on the high-elevation Qinghai-Tibetan Plateau, we found that warming not only increased plant species height but also altered species composition, collectively resulting in a taller plant community associated with increased net ecosystem productivity (NEP). Along a 1,500 km transect on the Plateau, taller plant community promoted NEP and soil carbon through associated chlorophyll content and other photosynthetic traits at the community level. Overall, plant community height as a dominant trait is associated with species composition and regulates ecosystem C sequestration in the high-elevation biome. This trait-based association provides new insights into predicting the direction, magnitude and sensitivity of ecosystem C fluxes in response to climate warming.

Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation.

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

Synthesis of (Furyl)Methyl Disulfides via Tandem Reaction of Conjugated Ene-Yne-Ketones with Acetyl-Masked Disulfide Nucleophiles.

In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.

Integrated multi-omics analysis and machine learning identify hub genes and potential mechanisms of resistance to immunotherapy in gastric cancer.

BACKGROUND: Patients with gastric cancer respond poorly to immunotherapy. There are still unknowns about the biomarkers associated with immunotherapy sensitivity and their underlying molecular mechanisms. METHODS: Gene expression data for gastric cancer were gathered from TCGA and GEO databases. DEGs associated with immunotherapy response came from ICBatlas. KEGG and GO analyses investigated pathways. Hub genes identification employed multiple machine algorithms. Associations between hub genes and signaling pathways, disease genes, immune cell infiltration, drug sensitivity, and prognostic predictions were explored via multi-omics analysis. Hub gene expression was validated through HPA and CCLE. Multiple algorithms pinpointed Cancer-Associated Fibroblasts genes (CAFs), with ten machine-learning methods generating CAFs scores for prognosis. Model gene expression was validated at the single-cell level using the TISCH database. RESULTS: We identified 201 upregulated and 935 downregulated DEGs. Three hub genes, namely CDH6, EGFLAM, and RASGRF2, were unveiled. These genes are implicated in diverse disease-related signaling pathways. Additionally, they exhibited significant correlations with disease-associated gene expression, immune cell infiltration, and drug sensitivity. Exploration of the HPA and CCLE databases exposed substantial expression variations across patients and cell lines for these genes. Subsequently, we identified CAFs-associated genes and established a robust prognostic model. The analysis in the TISCH database showed that the genes in this model were highly expressed in CAFs. CONCLUSIONS: The results unveil an association between CDH6, EGFLAM, and RASGRF2 and the immunotherapeutic response in gastric cancer. These genes hold potential as predictive biomarkers for gastric cancer immunotherapy resistance and prognostic assessment.

Regulating Mo-based alloy-oxide active interfaces for efficient alkaline hydrogen evolution assisted by hydrazine oxidation.

Improving the efficiency of overall water splitting (OWS) is crucial due to the slow four-electron transfer process in the oxygen evolution reaction (OER). The coupling of the thermodynamically favorable hydrazine oxidation reaction (HzOR) with the hydrogen evolution reaction (HER) significantly boosts hydrogen production. A Ru-decorated MoNi/MoO2 micropillar (Ru-MoNi/MoO2) has been synthesized using a hydrothermal followed by reduction annealing. Benefiting from Ru moderating the active interface of Mo-based alloys/oxides and the unique one-dimensional micropillar morphology. The synthesized Ru-MoNi/MoO2 exhibits outstanding bifunctional activity for HER and HzOR, achieving 10 mA cm-2 at merely -13 mV and -34 mV in 1 M KOH and 1 M KOH + 0.5 M N2H4, respectively. Notably, with Ru-MoNi/MoO2 in a dual-electrode setup, only 0.57 V is needed to achieve 50 mA cm-2, demonstrating good stability and facilitating hydrazine-assisted water splitting (OHzS). This work offers insights into the modulation of alloy/metal oxide active interfaces, contributing to the development of efficient bifunctional catalysts for HER and HzOR.

Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.

Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 µm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the second day and entered the cap stage on the fifth day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed in vivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.

Outcomes of standard EVAR for juxtarenal abdominal aortic aneurysm in patients unsuitable for fenestrated EVAR and open repair.

OBJECTIVE: To evaluate the long-term outcomes of standard endovascular aneurysm repair (S-EVAR) of juxtarenal abdominal aortic aneurysms (JAAAs). METHODS: Data of patients with JAAAs who were unsuitable for fenestrated endovascular aneurysm repair (F-EVAR) and open repair (OR) and underwent treatment from January 2015 to December 2021 were retrospectively reviewed. Computed tomography angiography and ultrasonography of the aorta were performed before discharge, at 6 and 12 months postoperatively, and annually thereafter. The main outcome measures were mortality, type Ia endoleaks, and reintervention. RESULTS: A total of 62 patients (mean age, 72.1 ± 7.3 years) underwent S-EVAR. The mean aneurysm length and diameter and the proximal neck length and diameter were 110.4 ± 30.9 mm, 57.2 ± 15.9 mm, 8.09 ± 0.97 mm, and 26.05 ± 0.49 mm, respectively. The mean suprarenal and infrarenal aortic angles were 162.9 ± 26° and 144.1 ± 31°, respectively. The mean follow-up duration was 40.6 ± 23.4 months and the 5-year survival rate was 62.2%. Six (9.8%) patients experienced type Ia endoleaks, of whom three underwent endovascular repair at 12, 18, and 24 months, one underwent conversion to OR for AAA rupture at 7 days and died, two had minor endoleaks and were kept under observation, and one declined reintervention at 36 months. The 5-year freedom from reintervention rate was 84.4%. The aneurysm diameter shrank in 50 cases (81%), remained stable in 5 cases (8%), and increased in 7 cases (11.3%). A suprarenal aortic angle <114° was associated with type Ia endoleak (p = .005). CONCLUSIONS: In patients unsuitable for F-EVAR and OR and with a suprarenal aortic angle >114°, the use of S-EVAR for JAAAs can be considered safe and effective. In this study, early and long-term postoperative outcomes demonstrated that S-EVAR achieved satisfactory results in the prevention of aneurysm rupture and associated mortality.

Using fs/QCA to explore the influencing factors of urban green infrastructure development and its combinational drivers: the case of the Yangtze River Delta region of China.

High levels of urban green infrastructure (UGI) development can help mitigate the climate, biodiversity, and habitat crises faced by cities and support the achievement of sustainable urban development. Based on the relevant data of 41 cities in the Yangtze River Delta region obtained from 2011 to 2020, this study measured the development level of natural and geographic conditions, economic development, urban construction, social and cultural development, and eco-environment quality and urban green infrastructure (UGI); evaluated the development trend of UGI in the region during the 12th Five-Year Plan and 13th Five-Year Plan by using entropy TOPSIS; and used fs/QCA to explain the high-level development path of each city toward the achievement of a green infrastructure. The results showed that (1) the development level of UGI in the Yangtze River Delta region decreases from southeast to northwest, and gradually decreases from Shanghai, Hangzhou, and other central cities. (2) There were several different configurations of high levels and non-high levels of UGI development drivers across regions, confirming the existence of multiple causality and asymmetry indices in the drivers of UGI. (3) During the "12th Five-Year Plan" and the "13th Five-Year Plan" period, the conditions needed to achieve a high level of UGI gradually became stricter, expanding from nature-social culture and urban construction-eco-environmental drivers to nature-urban construction, nature-social culture-eco-environmental, urban construction-economy-social culture-eco-environmental drivers. Research findings can provide greater guidance and implications for future sustainable urban development.

HAG-NET: Hiding Data and Adversarial Attacking with Generative Adversarial Network.

Recent studies on watermarking techniques based on image carriers have demonstrated new approaches that combine adversarial perturbations against steganalysis with embedding distortions. However, while these methods successfully counter convolutional neural network-based steganalysis, they do not adequately protect the data of the carrier itself. Recognizing the high sensitivity of Deep Neural Networks (DNNs) to small perturbations, we propose HAG-NET, a method based on image carriers, which is jointly trained by the encoder, decoder, and attacker. In this paper, the encoder generates Adversarial Steganographic Examples (ASEs) that are adversarial to the target classification network, thereby providing protection for the carrier data. Additionally, the decoder can recover secret data from ASEs. The experimental results demonstrate that ASEs produced by HAG-NET achieve an average success rate of over 99% on both the MNIST and CIFAR-10 datasets. ASEs generated with the attacker exhibit greater robustness in terms of attack ability, with an average increase of about 3.32%. Furthermore, our method, when compared with other generative stego examples under similar perturbation strength, contains significantly more information according to image information entropy measurements.

Paeonol promotes longevity and fitness in Caenorhabditis elegans through activating the DAF-16/FOXO and SKN-1/Nrf2 transcription factors.

Paeonol, as one of the most abundant plant-derived polyphenols, has multiple bioactivities including anti-inflammatory, anti-tumor, and anti-cardiovascular diseases. Nevertheless, the anti-aging effects and related mechanisms of paeonol are rarely reported. In this study, we found that paeonol significantly prolonged the mean lifespan of Caenorhabditis elegans (C. elegans) by 28.49% at a dose of 200 µM. Moreover, paeonol promoted the health of C. elegans by increasing the body bending and pharyngeal pumping rates and reducing the lipofuscin accumulation level. Meanwhile, paeonol induced the expression of stress-related genes or proteins by activating the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, which in turn enhanced oxidative and thermal stress tolerance. The mechanism behind the anti-aging effect of paeonol occurred by down-regulating the insulin/IGF-1 signaling (IIS) pathway. Our findings shed new light on the application of paeonol for longevity promotion and human health.

Novel application of the ferroptosis-related genes risk model associated with disulfidptosis in hepatocellular carcinoma prognosis and immune infiltration.

Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer and continues to pose a formidable challenge to human well-being and longevity, owing to its elevated incidence and mortality rates. Nevertheless, the quest for reliable predictive biomarkers for HCC remains ongoing. Recent research has demonstrated a close correlation between ferroptosis and disulfidptosis, two cellular processes, and cancer prognosis, suggesting their potential as predictive factors for HCC. In this study, we employed a combination of bioinformatics algorithms and machine learning techniques, leveraging RNA sequencing data, mutation profiles, and clinical data from HCC samples in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) databases, to develop a risk prognosis model based on genes associated with ferroptosis and disulfidptosis. We conducted an unsupervised clustering analysis, calculating a risk score (RS) to predict the prognosis of HCC using these genes. Clustering analysis revealed two distinct HCC clusters, each characterized by significantly different prognostic and immune features. The median RS stratified HCC samples in the TCGA, GEO, and ICGC cohorts into high-and low-risk groups. Importantly, RS emerged as an independent prognostic factor in all three cohorts, with the high-risk group demonstrating poorer prognosis and a more active immunosuppressive microenvironment. Additionally, the high-risk group exhibited higher expression levels of tumor mutation burden (TMB), immune checkpoints (ICs), and human leukocyte antigen (HLA), suggesting a heightened responsiveness to immunotherapy. A cancer stem cell infiltration analysis revealed a higher similarity between tumor cells and stem cells in the high-risk group. Furthermore, drug sensitivity analysis highlighted significant differences in response to antitumor drugs between the two risk groups. In summary, our risk prognostic model, constructed based on ferroptosis-related genes associated with disulfidptosis, effectively predicts HCC prognosis. These findings hold potential implications for patient stratification and clinical decision-making, offering valuable theoretical insights in this field.

Analysis of depression incidence and influence factors among middle-aged and elderly diabetic patients in China: based on CHARLS data.

BACKGROUND: To investigate the incidence of depression in middle-aged and elderly patients with diabetes in China and the influencing factors to provide a theoretical basis to improve the mental health of middle-aged and elderly patients with diabetes and formulate prevention, control, and intervention strategies. METHODS: The sample of this study was obtained from the China Health and Aging Tracking Survey (CHARLS) 2018 survey data, and middle-aged and older patients with diabetes(responding "Yes" to the questionnaire: "Have you ever been told by a doctor that you have diabetes or elevated blood glucose [including abnormal glucose tolerance and elevated fasting glucose]?") aged ≥ 45 years were selected as study subjects (n = 2,613 ). Depressive symptoms of the study subjects were determined using the simplified version of the Depression Scale for Epidemiological Surveys scores(a score ≥ 10 was defined as depression), influence factors were analyzed using binary logistic regression, and proportion of depressive symptoms was standardized using the sex ratio of the seventh census. RESULTS: Among the 2,613 middle-aged and elderly patients with diabetes, 1782 (68.2%) had depressive symptoms and 831 (31.8%) had no depressive symptoms. There were 481 (27.0%) patients aged 45-59 years, 978 (54.9%) aged 60-74 years, and 323 (18.1%) aged ≥ 75 years. The depression rate among middle-aged and elderly Chinese patients with diabetes after standardization correction was 67.5%. Binary logistic regression results showed that age, education level, life satisfaction, marital satisfaction, self-rated health grade, somatic pain, visual impairment, physical disability, and the presence of comorbid chronic diseases were factors that influenced the onset of depression in middle-aged and elderly Chinese patients with diabetes (P < 0.05). CONCLUSION: According to a survey analysis of the CHARLS 2018 data, depression is influenced by a combination of factors among middle-aged and elderly patients with diabetes in China. Therefore, for this population, targeted prevention and control should be carried out for key populations, such as middle-aged and elderly people, poor physical health, and low life satisfaction and marital satisfaction, from various dimensions (e.g., demographic and sociological factors, physical health status, and life satisfaction and marital satisfaction).

Transition-Metal-Free Disulfuration of Amides with Trisulfide Dioxides via Formation of Unaccessible S-S-N Bonds.

Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N-disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.

Constructing Hollow Microcubes SnS2 as Negative Electrode for Sodium-ion and Potassium-ion Batteries.

Sodium/potassium-ion batteries (NIBs and KIBs) are considered the most promising candidates for lithium-ion batteries in energy storage fields. Tin sulfide (SnS2) is regarded as an attractive negative candidate for NIBs and KIBs thanks to its superior power density, high-rate performance and natural richness. Nevertheless, the slow dynamics, the enormous volume change and the decomposition of polysulfide intermediates limit its practical application. Herein, microcubes SnS2 were prepared through sacrificial MnCO3 template-assisted and a facile solvothermal reaction strategy and their performance was investigated in Na and K-based cells. The unique hollow cubic structure and well-confined SnS2 nanosheets play an important role in Na+/K+ rapid kinetic and alleviating volume change. The effect of the carbon additives (Super P/C65) on the electrochemical properties were investigated thoroughly. The in operando and ex-situ characterization provide a piece of direct evidence to clarify the storage mechanism of such conversion-alloying type negative electrode materials.

The Growth Yield of Aminobacter niigataensis MSH1 on the Micropollutant 2,6-Dichlorobenzamide Decreases Substantially at Trace Substrate Concentrations.

2,6-Dichlorobenzamide (BAM) is an omnipresent micropollutant in European groundwaters. Aminobacter niigataensis MSH1 is a prime candidate for biologically treating BAM-contaminated groundwater since this organism is capable of utilizing BAM as a carbon and energy source. However, detailed information on the BAM degradation kinetics by MSH1 at trace concentrations is lacking, while this knowledge is required for predicting and optimizing the degradation process. Contaminating assimilable organic carbon (AOC) in media makes the biodegradation experiment a mixed-substrate assay and hampers exploration of pollutant degradation at trace concentrations. In this study, we examined how the BAM concentration affects MSH1 growth and BAM substrate utilization kinetics in a AOC-restricted background to avoid mixed-substrate conditions. Conventional Monod kinetic models were unable to predict kinetic parameters at low concentrations from kinetics determined at high concentrations. Growth yields on BAM were concentration-dependent and decreased substantially at trace concentrations; i.e., growth of MSH1 diminished until undetectable levels at BAM concentrations below 217 µg-C/L. Nevertheless, BAM degradation continued. Decreasing growth yields at lower BAM concentrations might relate to physiological adaptations to low substrate availability or decreased expression of downstream steps of the BAM catabolic pathway beyond 2,6-dichlorobenzoic acid (2,6-DCBA) that ultimately leads to Krebs cycle intermediates for growth and energy conservation.

A preventative role of nitrate for hypoxia-induced intestinal injury.

BACKGROUND: Studying effective interventions for hypoxia-induced injury is crucial, particularly in high-altitude areas. Symptoms stemming from intestinal injuries have a significant impact on the health of individuals transitioning from plains to plateau regions. This research explores the effects and mechanisms of nitrate supplementation in preventing hypoxia-induced intestinal injury. METHODS: A hypoxia survival mouse model was established using 7% O2 conditions. The intervention with 4 mM sodium nitrate (NaNO3) in drinking water commenced 7 days prior to hypoxia exposure. Weight monitoring, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), and intestinal permeability assays were employed for physiological, histological, and functional analyses. Quantitative PCR (qPCR), Western blot, and immunofluorescence were utilized to analyze the levels of tight junction (TJ) proteins and hypoxia-inducible factor 1α (Hif 1α). RNA sequencing (RNA-seq) identified nitrate's target, and chromatin immunoprecipitation (ChIP) verified the transcriptional impact of Hif 1α on TJ proteins. Villin-cre mice infected with AAV9-FLEX-EGFP-Hif 1α were used for mechanism validation. RESULTS: The results demonstrated that nitrate supplementation significantly alleviated small intestinal epithelial cell necrosis, intestinal permeability, disruption of TJs, and weight loss under hypoxia. Moreover, the nitrate-triggered enhancement of TJs is mediated by Hif 1α nuclear translocation and its subsequent transcriptional function. The effect of nitrate supplementation on TJs was largely attributed to the stimulation of the EGFR/PI3K/AKT/mTOR/Hif 1α signaling pathways. CONCLUSION: Nitrate serves as a novel approach in preventing hypoxia-induced intestinal injury, acting through Hif 1α activation to promote the transcription of TJ proteins. Furthermore, our study provides new and compelling evidence for the protective effects of nitrate in hypoxic conditions, especially at high altitudes.

A motif for B/O-site modulation in LaFeO3 towards boosted oxygen evolution.

Here, a series of transition metal (Ni) doped iron-based perovskite oxides LaFe1-xNixO3-δ (x = 0, 0.25, 0.5, 0.75, 1) were prepared, and then the perovskite oxide with the optimized nickel-iron ratio was doped with non-metallic elements (N). Experimental and theoretical investigations reveal that the co-doping breaks the traditional linear constraint relationship (GOOH - GOH = 3.2 eV) and the theoretical overvoltage is reduced from 0.64 V (LaFeO3-δ) to 0.44 V (LaFe0.5Ni0.5O3-δ/N). Specifically, Ni-doping can accelerate electron transfer and improve the conductivity. Moreover, N-doping can reduce the adsorption energy of *OH/*O and enhance the adsorption energy of *OOH. We demonstrated that the optimized cation and anion co-doped LaFe0.5Ni0.5O3-δ/N perovskite oxide exhibits an excellent OER performance, with a low overpotential of 270.6 mV at 10 mA cm-2 and a small Tafel slope of 65 mV dec-1 in 1 M KOH solution, markedly exceeding that of the parent perovskite oxide LaFeO3-δ (300.9 mV) and commercial IrO2 (289.1 mV). It also delivers decent durability with no significant degradation after a 35 h stability test. This work reveals the internal mechanism of perovskite oxide by doping cation and anion for water oxidation, which broadens the idea for the rational design of new perovskite-based sustainable energy catalysts.