Search

Abstract Background Primary osteoporosis has increasingly emerged as a major issue affecting human health, with a complex specific pathogenic mechanism. As a research hotspot, ferroptosis plays a vital role in the pathogenesis of primary osteoporosis, aiming to explore the link and specific target genes between ferroptosis and primary osteoporosis. Methods By utilizing TMT proteomics and bioinformatics analyses, we elucidated the linkages and key targets of the ferroptosis pathway in an ovariectomized osteoporotic rat model. Forty 12-week-old SD female rats were employed in the study, of which 20 female SD rats were ovariectomized as the OVX group and 20 female SD rats were employed as the SHAM group. At the end of the experiments, the femurs of the rats were excised for computed tomography tests and used for hematoxylin and eosin staining. Finally, we extracted bone tissue proteins for TMT proteomics analysis and protein blotting verification. Results The proteomics results of the VX and SHAM groups showed that 133 proteins were significantly changed, of which 91 proteins were upregulated and 42 proteins were downregulated, including TXN, TMSB4X, TFRC, TF, RELA, PARP14, CP, CAPG, and ADIPOQ. The expression of key proteins in the bone tissues was detected by protein blotting. The expression of TFR1, TFRC and TF was upregulated, whereas the expression of Cp, TXN and BMP-2 was downregulated. Conclusions TMT proteomics and functional enrichment analyses in our study substantiated that in osteoporosis, disturbances in lipid metabolism lead to the emergence of oxidative stress with iron homeostasis imbalance.

Abstract Background Patients with migraine often experience not only headache pain but also cognitive dysfunction, particularly in attention, which is frequently overlooked in both diagnosis and treatment. The influence of these attentional deficits on the pain-related clinical characteristics of migraine remains poorly understood, and clarifying this relationship could improve care strategies. Methods This study included 52 patients with migraine and 34 healthy controls. We employed the Attentional Network Test for Interactions and Vigilance–Executive and Arousal Components paradigm, combined with electroencephalography, to assess attentional deficits in patients with migraine, with an emphasis on phasic alerting, orienting, executive control, executive vigilance, and arousal vigilance. An extreme gradient boosting binary classifier was trained on features showing group differences to distinguish patients with migraine from healthy controls. Moreover, an extreme gradient boosting regression model was developed to predict clinical characteristics of patients with migraine using their attentional deficit features. Results For general performance, patients with migraine presented a larger inverse efficiency score, a higher prestimulus beta-band power spectral density and a lower gamma-band event-related synchronization at Cz electrode, and stronger high alpha-band activity at the primary visual cortex, compared to healthy controls. Although no behavior differences in three basic attentional networks were found, patients showed magnified N1 amplitude and prolonged latency of P2 for phasic alerting-trials as well as an increased orienting evoked-P1 amplitude. For vigilance function, improvements in the hit rate of executive vigilance-trials were exhibited in controls but not in patients. Besides, patients with migraine exhibited longer reaction time as well as larger variability in arousal vigilance-trials than controls. The binary classifier developed by such attentional deficit features achieved an F1 score of 0.762 and an accuracy of 0.779 in distinguishing patients with migraine from healthy controls. Crucially, the predicted value available from the regression model involving attentional deficit features significantly correlated with the real value for the frequency of headache. Conclusions Patients with migraine demonstrated significant attentional deficits, which can be used to differentiate migraine patients from healthy populations and to predict clinical characteristics. These findings highlight the need to address cognitive dysfunction, particularly attentional deficits, in the clinical management of migraine.

The impact of erbium (Er) on grain refinement in Al–Cu–Li alloys is limited by the thermodynamic instability of Al3Er inoculants. Nevertheless, the concurrent addition of both Er and Zr to Al–Cu–Li alloys results in a marked refinement of the average grain size. Er exerts a significant influence on the precipitation sequence within Al–Cu–Li alloys, promoting a complete transition from δ′ (Al3Li) and θ′ (Al2Cu) to T1 (Al2CuLi) precipitates during aging at 120 °C, thereby substantially enhancing both strength and ductility. Through high-resolution transmission electron microscopy (HRTEM), the underlying mechanism of the T1 nucleation by Er microalloying has been elucidated. It has been demonstrated that the presence of Er leads to the formation of solute enrichment regions (SERs) comprising Cu, Zn, Mg and Er. These SERs serve as catalysts for the development of Cu-rich atomic planes along the {111}Al, providing a direct precursor structure for T1 nucleation. Consequently, the synergistic microalloying of Zr and Er not only effectively refines the grain structure but also facilitates the elimination of the δ′ phase. The addition of Er facilitates the complete transformation of the δ′ phase into the strong and ductile T1 phase, resulting in a significant enhancement of the alloy's strength and ductility. Following 100 h of aging at 120 °C, the ultimate tensile strength has increased from 373 to 457 MPa, and the elongation after fracture has risen from 2.8% to 4.9%.

Abstract The direct co-conversion of methane and carbon dioxide into valuable chemicals has been a longstanding scientific pursuit for carbon neutrality and combating climate change. Herein, we present a photo-driven chemical process that reforms these two major greenhouse gases together to generate green methanol and CO, two high-valued industrial chemicals. Isotopic labeling and control experiments indicate an oxygen-atom-graft occurs, wherein CO2 transfers one O into the C–H bond of CH4 via photo-activated interfacial catalysis with AuPd nanoparticles supported on GaN. The photoexcited AuPd/GaN interface effectively orchestrates the CH4 oxidation and the CO2 reduction producing 13.66 mmol g−1 of CH3OH yield over 10 h. This design provides a solid scientific basis for the photo-driven oxygen-atom-grafting process to be further extended to visible light region.

Background/Aims The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

The reaction kinetics at the solid-liquid interface significantly affects the rate of electrocatalytic reactions. At the atomic and molecular levels, accurately identifying the structural evolution of active sites, the evolution of reaction intermediates, and the mechanism of catalytic reactions play an important role for designing efficient catalysts in electrochemical energy storage and conversion technologies, though it remains highly challenging. This review systematically scrutinizes recent achievements in the dynamic investigation of solid-liquid electrochemical interfaces during electrocatalysis, using in situ synchrotron X-ray absorption fine structure (SR-XAFS) and synchrotron Fourier-transform infrared spectroscopy (SR-FTIR). It provides a comprehensive discussion on the continuous development of in situ SR-XAFS and SR-FTIR, with particular emphasis on the content of multi-scale monitoring the structural evolution of active centers. Moreover, the review highlights the unique and powerful role of correlative SR-XAFS/FTIR in exploring the dynamic of solid-liquid electrochemical interfaces in mainstream research areas such as electrocatalytic water splitting, oxygen reduction, nitrate reduction, and carbon dioxide reduction. Finally, the challenges and prospects of identifying the kinetic behavior of solid-liquid electrocatalytic interfaces in electrocatalytic materials under working conditions. This review aims to offer ample, reliable, and complementary information on the dynamic evolution of the interface during the electrocatalytic process, thereby guiding the rational design of advanced catalytic materials with outstanding activity, selectivity, and stability.

Traditional Chinese medicine Gu Sui Bu (Drynaria fortunei J. Smith), has the effect of tonifying the kidneys and strengthening bone. There are many modern studies on the anti-osteoporosis pharmacological mechanism of Gu Sui Bu (Drynaria fortunei J. Smith) but no reports on the pharmacological mechanism of Gu Sui Bu (Drynaria fortunei J. Smith) improving cell pyroptosis and anti-osteoporosis have been found. Aim: This study aims to verify the changes in cellular standard indicators in postmenopausal osteoporosis, thereby revealing the participating mechanism of pyroptosis and the intervention effect of Gu Sui Bu (Drynaria fortunei J. Smith) . Methods: Gu Sui Bu (Drynaria fortunei J. Smith) subjected to UHPLC-Q-Orbitrap-MS/MS analysis, and the OVX rat model was constructed in vivo as the research object. It was divided into sham operation group (SHAM), ovariectomized osteoporosis model group (OVX) and Gu Sui Bu (Drynaria fortunei J. Smith) group (TFRD-L, TFRD-H). After 3 months of modeling, the medication group was treated with Gu Sui Bu (Drynaria fortunei J. Smith) and the samples were collected after 12 weeks of intervention. ELISA was used to detect the levels of Caspase-1, NLRP3, GSDMD, IL-1β, and IL-18 in rat serum; the right femur was taken for Micro-CT large bone microstructure scanning and femoral BMD detection; the femur was subjected to rat histopathology HE, TRAP staining; immunohistochemistry and immunofluorescence staining of rat histopathology were performed. WB and PCR were used to observe the expression of Osteoblasts and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD and RUNX2, IL-1β, and IL-18. Results: UHPLC-Q-Orbitrap-MS/MS analysis the main compounds in Gu Sui Bu (Drynaria fortunei J. Smith) samples were identified. These 9 chemical components are Palmitic acid, Fisetin, Caffeic acid, Naringin, Rutin, Uridine, Cafestol, Astilbin . Rat Micro-CT, The results of HE staining and TRAP showed that compared with the rats in the OVX group, the number of bone trabeculae in the rats in the Gu Sui Bu (Drynaria fortunei J. Smith) medication group (TFRD-L, TFRD-H) increased, became wider and thicker, and the bone density increased. Continuity increases and bone lacunae decrease. Rat serum ELISA, femoral tissue immunohistochemistry, immunofluorescence staining and WB, PCR showed that compared with the OVX group, Caspase-1, NLRP3, The expression levels of GSDMD and inflammation were reduced (p

With urbanisation and population growth, understanding spatial interactions in cities is increasingly vital for urban management. In recent decades, spatial interactions could be predicted accurately with the support of large GPS data, but anonymous trajectory data lacks semantic details, limiting predictions and behaviour understanding. To address this, we proposed a Semantic-Integrated Mobility Trajectory Model (SMTM), integrating social media check-in data, remote sensing imagery, and taxi trajectory data capable of accurately predict travel flow. Specifically, Convolutional Neural Networks (CNN) and Long Short Term Memory (LSTM) extract demographic insights, Graph Convolutional Networks (GCN) and Gate Recurrent Units (GRU) are incorporated to predict spatial interaction intensity. We conducted two case studies in New York City, U.S., and Ningbo, China, using taxi trips (over three million trips in New York and nearly one million trips in Ningbo) and social media check-in data (around 60,000 records for each city). Results demonstrate excellent performance over baselines. Furthermore, the integration of travel trajectories and census data revealed diverse travel preferences at various scales, including intra-region, inter-region, and inter-urban. The SMTM model contributes to optimising the design of public spaces and personalised recommendations.

Background Despite the successful application of immunotherapy, both innate and acquired resistance are typical in melanoma. Ferroptosis induction appears to be a potential strategy to enhance the effectiveness of immunotherapy. However, the relationship between the status of ferroptosis and the effectiveness of immunotherapy, as well as viable strategies to augment ferroptosis, remains unclear.Methods A screening of 200 cardiovascular drugs obtained from the Food and Drug Administration-approved drug library was conducted to identify the potential ferroptosis sensitizer. In vitro and in vivo experiments explored the effects of propafenone on ferroptosis in melanoma. Animal models and transcriptomic analyses evaluated the therapeutic effects and survival benefits of propafenone combined with immune checkpoint blockades (ICBs). The relationship between propafenone targets and the efficacy of ICBs was validated using the Xiangya melanoma data set and publicly available clinical data sets.Results Through large-scale drug screening of cardiovascular drugs, we identified propafenone, an anti-arrhythmia medication, as capable of synergizing with ferroptosis inducers in melanoma. Furthermore, we observed that propafenone, in combination with glutathione peroxidase 4 inhibitor RSL3, collaboratively induces mitochondrial-associated ferroptosis. Mechanistically, propafenone transcriptionally upregulates mitochondrial heme oxygenase 1 through the activation of the Jun N-terminal kinase (JNK)/JUN signaling pathway under RSL3 treatment, leading to overloaded ferrous iron and reactive oxygen species within the mitochondria. In xenograft models, the combination of propafenone and ferroptosis induction led to nearly complete tumor regression and prolonged survival. Consistently, propafenone enhances immunotherapy-induced tumorous ferroptosis and antitumor immunity in tumor-bearing mice. Significantly, patients exhibiting high levels of ferroptosis/JUN/HMOX1 exhibited improved efficacy of immunotherapy and prolonged progression-free survival.Conclusions Taken together, our findings suggest that propafenone holds promise as a candidate drug for enhancing the efficacy of immunotherapy and other ferroptosis-targeted therapies in the treatment of melanoma.

ObjectiveTo assess the prevalence and risk determinants of locomotive syndrome (LS) in geriatric cancer survivors in China. To generate evidence-based insights for the clinical prevention and intervention strategies concerning LS in this vulnerable population, emphasizing the need for integrated public health initiatives focused on maintaining mobility among geriatric cancer survivors.MethodsSix hundred geriatric cancer survivors were recruited at a hospital in China. A demographic questionnaire, the International Physical Activity Questionnaire-Short (IPAQ-S), and the Geriatric Locomotive Function Scale (GLFS-25) were administered. Survivors were stratified into three physical activity level (PAL) groups via IPAQ-S scores: low, medium, and high. LS was operationally defined via GLFS-25 scores, with cut-offs established for LS-1, LS-2, and LS-3. Elevated GLFS-25 scores signified deteriorated motor function (MF) and increased severity of LS. Data analysis was done to investigate the risk determinants to the occurrence and exacerbation of LS among geriatric cancer survivors.ResultsOf the 524 geriatric cancer survivors who completed the study, 292 (55.7%) were diagnosed with LS, including 152 (29%) categorized under LS-1, 52 (9.9%) under LS-2, and 88 (16.8%) under LS-3. Univariate analysis indicated that variations in exercise habits, prior occupational type, presence of tumor metastasis or recurrence, visual impairments, somatosensory abnormalities, and PAL were significantly associated with differing occurrences and severities of LS (p

Background: Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated. Methods: In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms. Results: OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103+DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota. Conclusions: FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.

Hydraulic oil leaks during mechanical maintenance, resulting in flushing wastewater contaminated with dispersed nano-oil droplets. In this study, 75 mg L−1 of polysilicate aluminum ferric (PSAF) was stirred at 350 rpm and the optimal chemical oxygen demand (COD) removal was 71%. The increase of PSAF led to more hydrolysis of Fe, and 1,175 cm−1 hydroxyl bridged with negative oil droplets. At the same molar concentration, PSAF hydrolyzes cationic metals more rapidly than polymeric aluminum chloride (PAC). PSAF forms flocs of smaller complex structures with greater bridging. The Al–O and Si–O peaks occurred at 611 and 1,138 cm−1, indicating the formation of Si–O–Fe and Si–O–Al bonds on the flocs surface. Higher stirring speeds did not change the free energy of the flocs surface γTot, mainly because the decrease in the van der Waals force (γLW) offset the increase of Lewis acid–base force (γAB). Preserving the non-polar surface, in summary, owing to its bridging abilities and affinity for non-polar surfaces, PSAF demonstrates superior efficiency over PAC in capturing and removing oil droplets. HIGHLIGHTS 75 mg L−1 of PSAF was stirred at 350 rpm and the optimal COD removal was 71%.; PSAF bridging was superior to PAC in terms of Si–O–Fe and Si–O–Al bonds.; PSAF forms flocs of smaller complex structures with greater bridging.; Higher stirring speeds did not change the non-polar surface of PSAF flocs to have good adsorption.;

Abstract Background Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. Methods 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. Results Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. Conclusions LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

Abstract This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2–2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 μm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 μm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.

Abstract Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

Background: Cognitive impairment is a common manifestation in patients with T2DM mellitus (T2DM). Ginsenoside Rg1 (GRg1) is the main active substance extracted from ginseng or Panax notoginseng. Methods: T2DM was induced by feeding rats with a high-sugar and high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) on an empty stomach. Subsequently, different concentrations of GRg1 (25, 50, 100 mg/kg/d) were used to intervene for 8 weeks and explore its therapeutic effects and potential mechanisms on cognitive impairment in T2DM rats. Results: Our data suggested that administration of GRg1 improved insulin resistance, specifically manifesting in a reduction of insulin resistance index by approximately 57.1 % with high doses of GRg1 (100 mg/kg/d). Besides, it has been observed to lower cholesterol, triglycerides, and low-density lipoprotein by approximately 20–50 % in T2DM rats. In addition, GRg1 treatment dramatically improved the spatial memory and learning ability in T2DM rats. Furthermore, administration of GRg1 to the T2DM rats dose-dependently up-regulated ERKs phosphorylation and blunted phosphorylation of JNKs and p38. Furthermore, GRg1 treatment also dose-dependently increased the expression of Bcl-2 but inhibited the expression of Bax and Caspase 3 expression in T2DM rats brain cortex and hippocampus neurons. Conclusion: GRg1 effectively improves mild cognitive impairment in T2DM rats by inhibiting oxidative stress and reducing the apoptosis of neurons in the cerebral cortex and hippocampus.

To date, the aging softening of Mg-Li-Zn based alloys has been a critical issue limiting their industrial application. Here, we design a new Mg-Li alloy that exhibits exceptional mechanical stability after solution treatment and then water quenching by means of a hitherto unrecognized mechanism. The results indicate that precipitation of a semi-coherent MgLi2(ZnAg) phase leads to rapid age-hardening of the Mg-Li alloy after water quenching, as evidenced by the Ag atoms in the precipitate. A massive solid solution of Ag atoms in the β-Li phase strengthens the stability of the alloy and retards the diffusion of Li atoms from the β phase into the α matrix during aging. Zn atoms in the MgLi2Zn precipitate are replaced by Ag atoms which explain the origin of age-hardening and inhibit the evolution of the substable strengthened phase MgLi2Zn to the equilibrium softened phase MgLiZn. This research may contribute to the theoretical basis for solving the age-softening problem of Mg-Li alloys.

The adoption and growth of functional magnetic resonance imaging (fMRI) technology, especially through the use of Pearson’s correlation (PC) for constructing brain functional networks (BFN), has significantly advanced brain disease diagnostics by uncovering the brain’s operational mechanisms and offering biomarkers for early detection. However, the PC always tends to make for a dense BFN, which violates the biological prior. Therefore, in practice, researchers use hard-threshold to remove weak connection edges or introduce l1-norm as a regularization term to obtain sparse BFNs. However, these approaches neglect the spatial neighborhood information between regions of interest (ROIs), and ROI with closer distances has higher connectivity prospects than ROI with farther distances due to the principle of simple wiring costs in resent studies. Thus, we propose a neighborhood structure-guided BFN estimation method in this article. In detail, we figure the ROIs’ Euclidean distances and sort them. Then, we apply the K-nearest neighbor (KNN) to find out the top K neighbors closest to the current ROIs, where each ROI’s K neighbors are independent of each other. We establish the connection relationship between the ROIs and these K neighbors and construct the global topology adjacency matrix according to the binary network. Connect ROI nodes with k nearest neighbors using edges to generate an adjacency graph, forming an adjacency matrix. Based on adjacency matrix, PC calculates the correlation coefficient between ROIs connected by edges, and generates the BFN. With the purpose of evaluating the performance of the introduced method, we utilize the estimated BFN for distinguishing individuals with mild cognitive impairment (MCI) from the healthy ones. Experimental outcomes imply this method attains better classification performance than the baselines. Additionally, we compared it with the most commonly used time series methods in deep learning. Results of the performance of K-nearest neighbor-Pearson’s correlation (K-PC) has some advantage over deep learning.

Immune checkpoint inhibitors enhance the tumor-killing ability of T-cells in non-small cell lung cancer (NSCLC), thereby boosting overall survival (OS) and transforming treatment for advanced stages. However, challenges persist, including low response rates and the absence of effective markers for candidate selection. This study evaluated the impact of hemoglobin, albumin, and platelet (HALP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on immunotherapy efficacy and survival in advanced NSCLC. Furthermore, the study aimed to develop a nomogram based on these parameters. Clinical and hematological data from patients diagnosed with NSCLC who received immunotherapy were analyzed. Efficacy was assessed using the immune Response Evaluation Criteria in Solid Tumors (iRECIST), and progression-free survival (PFS) and OS were analyzed. Prediction models were based on baseline and post-treatment HALP, NLR, and PLR. The 203 included patients had a median follow-up of 16 months, a median PFS (mPFS) of 7 months (6.0 – 8.0), while the median OS (mOS) was not available (24.0 – not available). The PLR before treatment (PLR0) was linked to a higher disease control rate (DCR) (odds ratio [OR] = 0.258), while initial immunotherapy and NLR after four cycles of treatment (NLR4C) significantly boosted the objective response rate (ORR). Cox regression showed that HALP before treatment (HALP0), HALP after four cycles of treatment (HALP4C), and NLR before treatment (NLR0) significantly influenced PFS. Additionally, HALP0, NLR0, and PLR after four cycles of treatment (PLR4C) were associated with OS. The C-indices for PFS and OS were 0.823 and 0.878, respectively, indicating good prediction accuracy. HALP, NLR, and PLR at various time points effectively predicted immunotherapy response in advanced NSCLC patients. Low HALP with high NLR and PLR indicated a poor prognosis. The findings can provide the basis for stratified randomized controlled trials (RCTs) in the future.

Coumarin, a phenolic compound, is a secondary metabolite produced by plants such as Tanga and Lime. Coumarin derivatives were prepared via Pechmann condensation. In this study, we performed in vitro and in vivo experiments to determine the antimicrobial and gut immune-regulatory functions of coumarin derivatives. For the in vitro antimicrobial activity assay, coumarin derivatives C1 and C2 were selected based on their pathogen-killing activity against various pathogenic microbes. We further demonstrated that the selected coumarin derivatives disrupted bacterial cell membranes. Next, we examined the regulatory function of the coumarin derivatives in gut inflammation using an infectious colitis model. In an in vivo infectious colitis model, administration of selected C1 coumarin derivatives reduced pathogen loads, the number of inflammatory immune cells (Th1 cells and Th17 cells), and inflammatory cytokine levels (IL-6 and IL-1b) in the intestinal tissue after pathogen infection. In addition, we found that the administration of C1 coumarin derivatives minimized abnormal gut microbiome shift-driven pathogen infection. Potential pathogenic gut microbes, such as Enterobacteriaceae and Staphylococcaceae, were increased by pathogen infection. However, this pathogenic microbial expansion was minimized and beneficial bacteria, such as Ligilactobacillus and Limosilactobacillus, increased with C1 coumarin derivative treatment. Functional gene enrichment assessment revealed that the relative abundance of genes associated with lipid and nucleotide metabolism was reduced by pathogen infection; however, this phenomenon was not observed in C1 coumarin derivative-treated animals. Collectively, our data suggest that C1 coumarin derivative is effective antibacterial agents that minimize pathogen-induced gut inflammation and abnormal gut microbiome modulation through their antibacterial activity.

For decades, it has been widely accepted that adding Mg to Al alloys decays Young's modulus of Al alloys. However, the fundamental mechanism for Young's modulus reduction is still pending. In this study, we experimentally produce the Al–Li alloys and Al–Li–Mg alloys using centrifugal casting and trace Young's modulus as a function of the evolution of their precipitation structures. Atomic-resolution high-angle-annular-dark-field (HAADF) imaging in scanning transmission electron microscopy (STEM) indicates that the precipitate sizes of Al–Li and Al–Li–Mg alloys are essentially the same in the early and late stages of aging. While atomic resolution HAADF suggests that although the lattice constants of δ′-Al3Li in Al–Li and Al–Li–Mg alloys (0.404 nm) are consistent in the early aging stage, it changes to 0.422 nm in the Al–Li–Mg alloy at the end of peak aging, showing a significant expansion to the same level as α-Al (0.421 nm). The nanoindentation results confirm that Young's modulus decreases strongly from 89.04 to 76.39 GPa for Al–Li–Mg alloys due to the lattice relaxation. Combining atomic-resolution HAADF and first-principles calculations, it has been found that Mg atoms diffuse into Al3(Li, Mg) crystals by replacing Li in the L12 δ′-Al3Li and thus doping the crystal. Further, it has been found that Mg atoms expand the spacing between Al–Al and Al–Li pairs thereby lowering the energy between Al–Al and Al–Li bonds, which in turn stretches their potential energy curves reducing Young's modulus.

Abstract Objective Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment. Methods We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC–MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison. Results We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor. Conclusion We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.

Abstract Single-atom catalysts, especially those with metal−N4 moieties, hold great promise for facilitating the oxygen reduction reaction. However, the symmetrical distribution of electrons within the metal−N4 moiety results in unsatisfactory adsorption strength of intermediates, thereby limiting their performance improvements. Herein, we present atomically coordination-regulated Co single-atom catalysts that comprise a symmetry-broken Cl−Co−N4 moiety, which serves to break the symmetrical electron distribution. In situ characterizations reveal the dynamic evolution of the symmetry-broken Cl−Co−N4 moiety into a coordination-reduced Cl−Co−N2 structure, effectively optimizing the 3d electron filling of Co sites toward a reduced d-band electron occupancy (d 5.8 → d 5.28) under reaction conditions for a fast four-electron oxygen reduction reaction process. As a result, the coordination-regulated Co single-atom catalysts deliver a large half-potential of 0.93 V and a mass activity of 5480 A gmetal −1. Importantly, a Zn-air battery using the coordination-regulated Co single-atom catalysts as the cathode also exhibits a large power density and excellent stability.

Abstract Background Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1 −/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

Abstract Although the acidic oxygen evolution reaction (OER) plays a crucial role in proton-exchange membrane water electrolysis (PEMWE) devices, challenges remain owing to the lack of efficient and acid-stable electrocatalysts. Herein, we present a low-iridium electrocatalyst in which tensile-strained iridium atoms are localized at manganese-oxide surface cation sites (TS-Ir/MnO2) for high and sustainable OER activity. In situ synchrotron characterizations reveal that the TS-Ir/MnO2 can trigger a continuous localized lattice oxygen-mediated (L-LOM) mechanism. In particular, the L-LOM process could substantially boost the adsorption and transformation of H2O molecules over the oxygen vacancies around the tensile-strained Ir sites and prevent further loss of lattice oxygen atoms in the inner MnO2 bulk to optimize the structural integrity of the catalyst. Importantly, the resultant PEMWE device fabricated using TS-Ir/MnO2 delivers a current density of 500 mA cm−2 and operates stably for 200 h.

Abstract In this paper, we investigate the existence of mild solutions as well as optimal controls for non-autonomous impulsive evolution equations with nonlocal conditions. Using the Schauder’s fixed-point theorem as well as the theory of evolution family, we prove the existence of mild solutions for the concerned problem. Furthermore, without the Lipschitz continuity of the nonlinear term, the optimal control result is derived by setting up minimizing sequences twice. An example is given of the application of the results.

High-wind structures were identified in the Cross-Calibrated Multi-Platform (CCMP) ocean wind vector reanalysis for comparison with winds measured by satellite radiometers, scatterometers, and synthetic aperture radar (SAR) instruments from February to October 2023. The comparison aims to evaluate bias, uncertainty, and spatial correlations with the goal of enhancing the accuracy of ocean wind datasets during tropical cyclones (TCs). In 10° longitude × 10° latitude blocks, each containing a TC, Soil Moisture Active Passive (SMAP) and Advanced Microwave Scanning Radiometer 2 (AMSR2) winds are 6.5 and 4.8% higher than CCMP, while Advanced Scatterometer (ASCATB) is 0.8% lower. For extratropical cyclones, AMSR2 and SMAP also show stronger winds with a 5% difference, and ASCATB is about 0.3% weaker compared to CCMP. The comparison between SAR and CCMP for TC winds, sampled at the locations and time frames of SAR tiles, indicates that SAR winds around TCs are about 9% higher than CCMP winds. Using empirically defined TC structural indices, we find that the TCs observed by CCMP are shifted in locations and lack a compact core region. A Random Forest (RF) regressor was applied to TCs in CCMP with corresponding SAR observations, nearly correcting the full magnitude of low bias in CCMP statistically, with a 15 m/s correction in the core region. The hierarchy of importance among the predictors is as follows: CCMP wind speed (62%), distance of SAR pixels to the eye region (21%) and eye center (7%), and distance of CCMP pixels to the eye region (5%) and eye center (5%).

The hydrological cycle is altered by climate change and human activities, amplifying extreme precipitation and heightening the flood risk regionally and globally. It is imperative to explore the future possible alterations in flood risk at the regional scale. Focusing on the Hanjiang river basin (HRB), this study develops a framework for establishing a scientific assessment of spatio-temporal dynamics of future flood risks under multiple future scenarios. In this framework, a GCMs statistical downscaling method based on machine learning is used to project future precipitation, the PLUS model is used to project future land use, the digitwining watershed model (DWM) is used to project future runoff, and the entropy weight method is used to calculate risk. Six extreme precipitation indices are calculated to project the spatio-temporal patterns of future precipitation extremes in the HRB. The results of this study show that the intensity (Rx1day, Rx5day, PRCPTOT, SDII), frequency (R20m), and duration (CWD) of future precipitation extremes will be consistently increasing over the HRB during the 21st century. The high values of extreme precipitation indices in the HRB are primarily located in the southeast and southwest. The future annual average runoff in the upper HRB during the near-term (2023–2042) and mid-term (2043–2062) is projected to decrease in comparison to the baseline period (1995–2014), with the exception of that during the mid-term under the SSP5-8.5 scenario. The high flood risk center in the future will be distributed in the southwestern region of the upper HRB. The proportions of areas with high and medium–high flood risk in the upper HRB will increase significantly. Under the SSP5-8.5 scenario, the area percentage with high flood risk during the future mid-term will reach 24.02%. The findings of this study will facilitate local governments in formulating effective strategic plans for future flood control management.

Abstract Aluminum‐lithium (Al‐Li) alloy is one of the most promising lightweight structural materials in the aeronautic and aerospace industries. The key to achieving their excellent mechanical properties lies in tailoring T1 strengthening precipitates; however, the nucleation of such nanoparticles remains unknown. Combining atomic resolution HAADF‐STEM with first‐principles calculations based on the density functional theory (DFT), here, we report a counterintuitive nucleation mechanism of the T1 that evolves from an Eshelby inclusion with unstable stacking faults. This precursor is accelerated by Ag‐Mg clusters to reduce the barrier, forming the structural framework. In addition, these Ag‐Mg clusters trap the free Cu and Li to prepare the chemical compositions for T1. Our findings provide a new perspective on the phase transformations of complex precipitates through solute clusters in terms of geometric structure and chemical bonding functions.

Diverse factors and beliefs define treatment decisions of culturally and linguistically diverse patients. Recognizing, understanding and respecting these enable us to walk with them on their cancer journey, even if it may be the road less traveled.

Abstract Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone‐related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

The Statewide (formerly Southern) California Earthquake Center (SCEC) conducts multidisciplinary earthquake system science research that aims to develop predictive models of earthquake processes, and to produce accurate seismic hazard information that can improve societal preparedness and resiliency to earthquake hazards. As part of this program, SCEC has developed the CyberShake platform, which calculates physics-based probabilistic seismic hazard analysis (PSHA) models for regions with high-quality seismic velocity and fault models. The CyberShake platform implements a sophisticated computational workflow that includes over 15 individual codes written by 6 developers. These codes are heterogeneous, ranging from short-running high-throughput serial CPU codes to large, long-running, parallel GPU codes. Additionally, CyberShake simulation campaigns are computationally extensive, typically producing tens of terabytes of meaningful scientific data and metadata over several months of around-the-clock execution on leadership-class supercomputers. To meet the needs of the CyberShake platform, we have developed an extreme-scale workflow stack, including the Pegasus Workflow Management System, HTCondor, Globus, and custom tools. We present this workflow software stack and identify how the CyberShake platform and supporting tools enable us to meet a variety of challenges that come with large-scale simulations, such as automated remote job submission, data management, and verification and validation. This platform enabled us to perform our most recent simulation campaign, CyberShake Study 22.12, from December 2022 to April 2023. During this time, our workflow tools executed approximately 32,000 jobs, and used up to 73% of the Summit system at Oak Ridge Leadership Computing Facility. Our workflow tools managed about 2.5 PB of total temporary and output data, and automatically staged 19 million output files totaling 74 TB back to archival storage on the University of Southern California's Center for Advanced Research Computing systems, including file-based relational data and large binary files to efficiently store millions of simulated seismograms. CyberShake extreme-scale workflows have generated simulation-based probabilistic seismic hazard models that are being used by seismological, engineering, and governmental communities.

Abstract On behalf of the journal, AGU, and the scientific community, the editors of Geophysical Research Letters would like to sincerely thank those who reviewed manuscripts for us in 2023. The hours reading and commenting on manuscripts not only improve the manuscripts, but also increase the scientific rigor of future research in the field. With the advent of AGU's data policy, many reviewers have also helped immensely to evaluate the accessibility and availability of data, and many have provided insightful comments that helped to improve the data presentation and quality. We greatly appreciate the assistance of the reviewers in advancing open science, which is a key objective of AGU's data policy. We particularly appreciate the timely reviews in light of the demands imposed by the rapid review process at Geophysical Research Letters. We received 4,512 submissions in 2023 and 5,112 reviewers contributed to their evaluation by providing 8,587 reviews in total. We deeply appreciate their contributions.

To overcome the limited application forms and inadequate therapeutic effects of 3D-printed scaffolds and osteogenic drug carriers. Nonetheless, concerns persist regarding the negative effects of burst and nonsustained release. In this study, we further enhanced the osteoinductive potential of 3D-printed BAG scaffolds by coating them with simvastatin (SIM) and poly(lactic-co-glycolic acid) (PLGA) with sustained release properties. Morphological assessment through SEM revealed evenly coated 3D-printed BAG scaffolds (BAG/PLGA/SIM), which showed sustained SIM release properties in vitro. The SIM released from BAG/PLGA/SIM still exhibited osteogenic activity in the augmentation of ALP activity and mineralization in mesenchymal stem cells. In an animal study of rat calvarial bone defects, both SIM-loaded BAG scaffolds, BAG/PLGA/SIM and BAG/PLGA/5 × SIM, significantly improved bone regeneration. Moreover, the IHC analysis of BMP2 and vWF expression also exhibited significant increases in both SIM-loaded BAG scaffolds. Notably, a higher SIM concentration (BAG/PLGA/5 × SIM) did not outperform a lower SIM concentration (BAG/PLGA/SIM) in promoting new bone formation. In conclusion, BAG/PLGA/SIM scaffolds could provide an excellent 3D architecture with sustained SIM release properties in vitro and excellent osteogenic properties for bone repair in vivo. The drug-loading method on 3D-printed BAG scaffolds could provide an alternative strategy for the development of multifunctional scaffolds for clinical applications.

This study reconstructs the Early Pleistocene paleoenvironment of the Yuanmou Basin through coproecology of the third member of the Yuanmou Formation. We examined 38 exceptionally well-preserved coprolites from a new fossil locality, and attributed the putative defecating agent to the hypercarnivorous diet canid, Sinocuon yuanmouensis through geochemical and quantitative analyses. A new ichnogenus and ichnospecies, Cuocopros yuanmouensis igen. et. isp. nov., was established based on distinctive characteristics. Multi-disciplinary analysis, including sediment palynology and lithostratigraphy, helped primarily reconstruct a significant climatic event during the early Pleistocene, coinciding with the emergence of Yuanmou Man during the fourth member of the Yuanmou Formation's deposition. The findings provide insights into coexistence between canids, hyaenas, hominoids, and other fauna, revealing a rich paleoecosystem and food chain in the region's history. This study contributes to understanding the complex ecological dynamics during this period in the Yuanmou Basin.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P

Pure water splitting by charged semiconductors and solar photons to concurrently generate H2 and O2 molecules has gained notable attention due to worldwide clean energy generation and storage. Despite significant advancements, challenges facing severe carrier recombination and sluggish electron transport continue to hinder the intrinsic efficiency of water splitting. Here, we fabricate two-dimensional graphitic carbon nitride-hybridized sulfur thionic polymorphs (CN/S100/S010 junctions) by incorporating photoactive semiconductors within lateral nanosheets. As a result, the charge rectification effect within the coplanar graphitic carbon nitride/S100/S010 junctions is induced by well-designed driving forces: favorable band offsets and cascade polarized surface work functions. During the water splitting process, the photogenerated electrons are sequentially transferred from graphitic carbon nitride to element semiconductor sulfur {100} and subsequently oriented to sulfur {010} facets. This unique behavior of charge migration within CN/S100/S010 photocatalysts contributes to impressive rates of H2 and O2 production, reaching 740 and 363 µmol g−1·h−1, respectively, nearly 13-fold higher than that of the parent carbon nitride. Comprehensive spectroscopic and theoretical analyses confirm the formation of CN/S100/S010 hierarchies with long-lived charge carriers during hydrogen energy production. This work introduces novel avenues for automatically orienting photogenerated carriers and holds promising prospects for clean energy production.

Inflow and water demand prediction plays an important role in reservoir operation rulemaking. Uncertainties in meteorological and hydrological modeling increase the complexity of inflow and water demand prediction, which are not sufficiently considered in conventional inflow and water demand prediction. Thus, this study took cascade reservoirs as the research object. These cascade reservoirs were located in the mainstream of the Yellow River Basin (YRB). A three-step framework was proposed: (1) developing a distributed Soil & Water Assessment Tool (SWAT) model to determine historical and future water availability in the reservoirs; (2) constructing the AquaCrop agricultural irrigation water demand model to predict future water demand of water users at 264 nodes (reservoirs and hydrological stations) in the YRB; (3) developing an optimal regulation model of cascade reservoirs in the YRB mainstream to quantitively determine the influence of future environmental changes on hydropower generation and water supply benefits of cascade reservoirs. The results indicate that the inflow of cascade reservoirs increased in the flood season and decreased significantly during the non-flood season compared with that in the historical period (1970–2016). However, there was a slight increase in the agricultural irrigation water demand, and the contradiction became more prominent between water resource supply and demand. During the future period (2020–2050), the guaranteed rate of hydropower generation and water supply in the YRB’s lower reaches will increase significantly. Uncertainties in climate models greatly impact hydropower generation benefits and reservoir water supply, especially in the flood season. These findings can facilitate the understanding of the complexity of hydropower management and production of cascade reservoirs under future environmental changes (inflow and demand) and encourage the use of regulation models for impact assessment studies and adaptive reservoir management to mitigate climate change.