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Abstract The rocket-based combined-cycle (RBCC) engine is regarded as one of the most viable propulsion systems for single-stage-to-orbit launch vehicles. Because of the relatively low total temperature of the incoming flow, it is difficult to maintain sustained and efficient subsonic combustion when the rocket engine is turned off. Mode transition and its control have also become critical techniques in the RBCC study. In the current work, it is proposed for the first time to improve the performance of RBCC engines in mode transition by using plasma combustion support. The numerical simulation and validation were conducted on the full path configuration of the RBCC engine, which is suitable for wide range operation. The impact of multi-channel gliding arc (MCGA) plasma-assisted combustion technology on the flow field was investigated during the transition phases from RBCC ejector/ramjet mode to ramjet/scramjet mode. The results show that: Adding arc plasma into the cavities at low Mach numbers promotes the heat release of the fuel, expanding the high-temperature flame range in the combustor. Although it weakens the ability of some air inlet to capture air, it overall increases engine thrust and diminishes aerodynamic drag during the transition process from ejector/ramjet mode. At high Mach numbers, the fast incoming flow speed results in the inability of the fuel to mix and burn with air in a timely manner, resulting in poor heat release and work performance. However, the addition of arc plasma for combustion support using the same mode transition method reduces the thrust fluctuation of the RBCC engine during the ramjet/scramjet mode transition process, greatly reducing the time required for mode transition, reducing engine resistance, and significantly improving engine thrust.

Panax ginseng, a venerable herb in traditional Chinese medicine, boasts a rich history of usage in the treatment of dementia, particularly in its various manifestations. However, despite its long-standing popularity and empirical evidence of effectiveness, the precise mechanisms underlying its therapeutic actions have remained elusive. Currently, research on pharmacodynamic components and mechanisms predominantly utilizes serum pharmacology and metabolomics research methods that are based on liquid chromatography-mass spectrometry technology. However, these methods are unable to capture the spatial distribution information of relevant substances, leading to a lack of comprehensive understanding of the pharmacodynamic components and their underlying mechanisms. To bridge this gap in knowledge, a method of spatial metabolomics and air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), was used to delve into the molecular mechanisms of Panax ginseng in treating Alzheimer’s disease (AD). The pharmacodynamic results demonstrated that Panax ginseng extract can significantly improve the state of brain pathological damage and spatial learning memory ability in AD model rats. This finding highlights the potential of ginseng as a therapeutic agent in AD management. Furthermore, the metabolomics analysis revealed that Panax ginseng modulates the levels of 19 biomarkers that are intricately linked to AD. These biomarkers span across 8 key metabolic pathways, including arginine and proline metabolism, purine metabolism, the tricarboxylic acid (TCA) cycle, and fatty acid metabolism. These pathways are essential for maintaining neuronal health and function, and their dysregulation is often associated with the pathogenesis of AD. Importantly, the study identified 7 active ginseng constituents that accumulate in brain tissue. These compounds work in a holistic manner to treat AD by modulating metabolites related to neuroinflammation, neuronal damage, energy deficits, and abnormal fatty acid metabolism. The comprehensive approach suggests that Panax ginseng may offer a multifaceted therapeutic strategy for AD. The unique capabilities of mass spectrometry imaging allow to analyze the spatial distribution of both endogenous and exogenous substances in parallel. This correspondence not only provides a deeper understanding of the specific effects of drug components, but also sheds light on how these components interact with the body’s endogenous metabolic networks to exert their therapeutic effects. In conclusion, the study provides new light on the mechanisms of action of Panax ginseng in treating AD and paves the way for future research and clinical applications of the ancient herb.

Abstract The fibrosis‐4 index (FIB‐4) is a noninvasive fibrosis test that is recommended for patients who are at risk of developing hepatic fibrosis. The aim of the study was to explore the correlation between FIB‐4 index and the decline of cognitive function among older patients with hypertension. The study used a cross‐sectional design to analyze data obtained from the NHANES 2011–2014. The significance of the FIB‐4 index correlation with cognitive function in individuals over the age of 60 was evaluated via multivariate regression models. The nonlinear link was described and fitted smoothed curves. There were a total of 2039 participants in the study, and those with a higher FIB‐4 index were more susceptible to developing cognitive decline. In the completely adjusted model, the association remained statistically significant between the FIB‐4 index and poor cognitive function as measured by CERAD: Total Score (OR = 0.72, 0.57−0.91), Animal Fluency Score (OR = 0.66, 0.48−0.91), and Digit Symbol Score (OR = 0.36, 0.17−0.77). A nonlinear association was found between the FIB‐4 and poor cognitive ability: Total Score, CERAD: Score Delayed Recall, Digit Symbol Score, and Animal Fluency Score. In elderly patients with hypertension, a high FIB‐4 index is correlated with an increased prevalence of cognitive decline. Hence, the FIB‐4 index could potentially serve as a valuable tool for determining individuals with hypertension who are susceptible to both liver‐related complications and cognitive impairment.

Metabolizing ellagic acid (EA) to urolithin A with numerous bioactivities significantly improve the nutritional value of food rich in EA. In the present study, Streptococcus thermophilus FUA329 was applied to prepare pomegranate juice yogurt. The best process formula was investigated through single-factor experiments and response surface methodology. With S. thermophilus CGMCC1.8748 as control, the viability of strain, rheological properties and antioxidant activity of pomegranate juice yogurt fermented with strain FUA329 were evaluated. The content of urolithin A in pomegranate juice yogurt fermented with strain FUA329 were analyzed by high-performance liquid chromatography. The results showed that the optimal fermentation conditions for preparing pomegranate juice yogurt by S. thermophilus FUA329 were 15.79% pomegranate juice content, 7.08% sucrose content and 3.04% starter inoculum size, fermentation at 37 ℃ for 7 h and comprehensive sensory score was 79.4 points. Under the optimal conditions, the results of basic indicators showed that yogurt acidity was (82.5±1.3)°T, whey precipitation was 9.6%±0.97%, color difference was 68.17±2.75, bacterial activity was 2.01±0.31 (OD600). In terms of antioxidant activity, DPPH radical, ABTS+ radical and superoxide anion radical scavenging rates of fermented pomegranate juice yogurt by strain FUA329 were 82.87%±1.48%, 88.20%±2.10% and 76.92%±1.02%, respectively, which was significantly better than plain yogurt fermented by strain FUA329 and pomegranate juice yogurt fermented by S. thermophilus CGMCC1.8748. In addition, urolithin A content was 3.31 μmol/L in fermented pomegranate juice yogurt by strain FUA329 after 7 h. The results of this study would provide a theoretical basis for fermenting a functional pomegranate juice yogurt, and lay a foundation for the development and utilization of S. thermophilus FUA329.

In order to evaluate the effect of Streptococcus thermophilus fermentation on green tea extract and its storage characteristics, this study used Streptococcus thermophilus FUA329 and S. thermophilus ST1.8748 (control group) to conduct experiments on green tea extracts. After fermentation and storage at 4 ℃ for 0, 30, 60, 120 and 180 d, pH, viable bacterial count, tea polyphenol content, ellagic acid content, and urolithin A content were used as the main evaluation indicators, combined with anti-oxidation activity to evaluate the storage quality of fermented green tea extract. The results showed that compared with the S. thermophilus ST1.8748 control group, the pH of S. thermophilus FUA329 fermented green tea extract during the storage period was between 5.39 and 5.71. The highest number of viable bacteria at 48 h was 9.97×108 CFU/mL. The content of tea polyphenols gradually decreased and the ellagic acid content tended to be stable. Urolithin A was produced at 48 h, and its concentration was 0.664 μmol/L. The antioxidant activity was always maintained at a high level. In summary, S. thermophilus FUA329 fermented green tea extract can significantly delay the quality decline and nutrient loss of green tea extract during storage.

Aiming at the task assignment problem of heterogeneous UAV performing multi-type fixed tasks on the ground, a task allocation method based on Cooperative Multiple Task Allocation Problem (CMTAP) and Modified Chimp Optimization Algorithm (MChOA) is proposed. Firstly, the CMTAP model is established, and the combat scene is depicted by setting the elements in the quad, and a multi-objective evaluation function with the highest total return, the lowest threat cost, and the shortest total flight range is established. Secondly, the MChOA algorithm is used to complete the model solving: the chaotic reverse learning strategy is adopted to improve the diversity of the intial population distribution. In the iteration stage, the global and local search capabilities of the algorithm are better balanced by adopting the dynamic adjustment strategy of preemptive behavior. Comparative experiments show that compared with the original algorithm, the resulting task allocation scheme reduces the average total voyage in the two scale scenarios by 22.6% and 21.1%, respectively, while maintaining a higher task gain and a lower threat cost.

Abstract Background Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). Methods Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI). Results In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = −0.8, P

ABSTRACT: High-yield dairy cows typically undergo intense cellular metabolism, leading to oxidative stress in their mammary tissues. Our study found that compared with ordinary cows, these high-yield cows had significantly elevated levels of H2O2, lipoperoxidase, and total antioxidant capacity in their blood. This increased oxidative stress is associated with heightened expression of genes such as GCLC, GCLM, and SIRT1 and proteins such as SIRT1 in the mammary tissue of high-yield cows. We stimulated MAC-T cells with H2O2 at a concentration equal to the average H2O2 level in the serum of ethically high-yielding cows, as detected by an assay kit. Our observations revealed that short-term exposure (12 h) to H2O2 upregulated the expression of the SIRT1 gene and SIRT1 protein. It also increased gene expression for SOD2, CAT, GCLC, GCLM, PGC-1α, and NQO1, elevated the phosphorylation of AMPK, and enhanced protein expression of PGC-1α, NQO1, Nrf2, and HO-1, as well as reduced the phosphorylation of NF-κB. Additionally, short-term H2O2 stimulation resulted in increased total antioxidant capacity and levels of superoxide dismutase, glutathione, and catalase in the mammary epithelial cells of dairy cows. In contrast, prolonged exposure to H2O2 (24 h) yielded opposite results, indicating reduced antioxidant capacity. Further investigation showed that the SIRT1 inhibitor EX 527 could reverse the enhanced cellular antioxidant capacity triggered by short-term oxidative stress. However, it is crucial to note that although 12 h of H2O2 stimulation improved antioxidant capacity, reactive oxygen species (ROS) and malondialdehyde (MDA) levels inside the cell gradually increased over time, suggesting greater damage under long-term stimulation. Conversely, the SIRT1 activator SRT 2104 could reverse the reduced cellular antioxidant capacity caused by long-term oxidative stress and significantly inhibit the accumulation of ROS and MDA. Notably, SRT 2104 demonstrated similar effects in MAC-T cells during lactation. In summary, SIRT1 plays a crucial role in regulating the antioxidant capacity of mammary epithelial cells in dairy cows. This discovery provides valuable insights into the antioxidant mechanisms of mammary cells, which can serve as a theoretical foundation for future mammary health strategies.

To determine the promoting effects of enzyme hydrolysis products of Larimichthys polyactis on the proliferation of Streptococcus thermophilus FUA329. The in vitro antioxidant activity of the enzymatic hydrolysis with different molecular weights were determined. Papain was selected for the enzymatic hydrolysis of its by-products on the basis of selecting different enzymes to hydrolyze the processing by-products of Larimichthys polyactis. Taking the proliferative effect of enzymatic degradation products on Streptococcus thermophilus as an indicator of evaluation. The enzymatic hydrolysis conditions were optimized through single factor and response surface methodology. The in vitro antioxidant activity of the hydrolysis products of the by-products of Larimichthys polyactis (HPBL) were determined. The results showed that the best enzymatic hydrolysis conditions included the hydrolysis time, material-liquid ratio and enzyme loading were 5 h, 1:5.1 (w/v) and 2.8% (w/v), respectively. The HPBL prepared under the optimized conditions was separated by ultrafiltration into four fragments, according to the molecular weight: >10000 Da, 5000~10000 Da, 3000~5000 Da,

Abstract To date, the types of fuels used in pottery kilns during the Western Zhou Dynasty have not been adequately addressed. Samples from updraft kilns and semi-downdraft kilns at the Fengjing site, the capital in the late Western Zhou period, were selected for analysis. Through phytolith and wood charcoal analysis, various grasses mainly Panicoideae, Pooideae, and Eragrostidoideae, as well as millet, rice, and wheat crops were identified. Additionally, wood primarily from trees of the Quercus, Ulmus, and Liquidambar taxa was found. These findings suggest that different pottery kilns used similar fuels, demonstrating a broad-spectrum rather than specialized fuel utilization during the Zhou period.

Abstract Background Maxillary expansion is an important treatment method for maxillary transverse hypoplasia. Different methods of maxillary expansion should be carried out depending on the midpalatal suture maturation levels, and the diagnosis was validated by palatal plane cone beam computed tomography (CBCT) images by orthodontists, while such a method suffered from low efficiency and strong subjectivity. This study develops and evaluates an enhanced vision transformer (ViT) to automatically classify CBCT images of midpalatal sutures with different maturation stages. Methods In recent years, the use of convolutional neural network (CNN) to classify images of midpalatal suture with different maturation stages has brought positive significance to the decision of the clinical maxillary expansion method. However, CNN cannot adequately learn the long-distance dependencies between images and features, which are also required for global recognition of midpalatal suture CBCT images. The Self-Attention of ViT has the function of capturing the relationship between long-distance pixels of the image. However, it lacks the inductive bias of CNN and needs more data training. To solve this problem, a CNN-enhanced ViT model based on transfer learning is proposed to classify midpalatal suture CBCT images. In this study, 2518 CBCT images of the palate plane are collected, and the images are divided into 1259 images as the training set, 506 images as the verification set, and 753 images as the test set. After the training set image preprocessing, the CNN-enhanced ViT model is trained and adjusted, and the generalization ability of the model is tested on the test set. Results The classification accuracy of our proposed ViT model is 95.75%, and its Macro-averaging Area under the receiver operating characteristic Curve (AUC) and Micro-averaging AUC are 97.89% and 98.36% respectively on our data test set. The classification accuracy of the best performing CNN model EfficientnetV2_S was 93.76% on our data test set. The classification accuracy of the clinician is 89.10% on our data test set. Conclusions The experimental results show that this method can effectively complete CBCT images classification of midpalatal suture maturation stages, and the performance is better than a clinician. Therefore, the model can provide a valuable reference for orthodontists and assist them in making correct a diagnosis.

Abstract Several (inter)national longitudinal dementia observational datasets encompassing demographic information, neuroimaging, biomarkers, neuropsychological evaluations, and muti-omics data, have ushered in a new era of potential for integrating machine learning (ML) into dementia research and clinical practice. ML, with its proficiency in handling multi-modal and high-dimensional data, has emerged as an innovative technique to facilitate early diagnosis, differential diagnosis, and to predict onset and progression of mild cognitive impairment and dementia. In this review, we evaluate current and potential applications of ML, including its history in dementia research, how it compares to traditional statistics, the types of datasets it uses and the general workflow. Moreover, we identify the technical barriers and challenges of ML implementations in clinical practice. Overall, this review provides a comprehensive understanding of ML with non-technical explanations for broader accessibility to biomedical scientists and clinicians.

Abstract Background To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). Method Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. Result As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin’s and lymphoma, Hodgkin’s), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. Conclusion ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

When vibrations generated by marine machinery propagate through a ship’s hull into the ocean, they produce low-frequency radiated noise with distinct “acoustic fingerprint” characteristics. This noise, characterized by stable and concentrated energy, long transmission distances, and difficulty in elimination, becomes the primary target for enemy sonar detection. Active vibration isolation serves as a critical method for reducing low-frequency vibrations in ships and enhancing their acoustic stealth performance. However, control challenges persist, including multi-frequency excitation, frequency fluctuation, multi-channel coupling, and slow convergence speed. To address these issues, this paper introduced an innovative multi-channel decentralized decoupling filtered-x least mean square (DMFxLMS) algorithm. Firstly, a recursive least squares identification algorithm with a forgetting factor was proposed, taking into account the characteristics of single-input, multi-output and multi-input, and multi-output control systems, effectively enhancing the algorithm’s convergence speed and control accuracy. Secondly, based on the decentralized decoupling control concept, the multi-channel control system was simplified into parallel single-channel control loops. The control weight coefficient updates were only related to adjacent error signals, significantly reducing the algorithm’s computational complexity. Thirdly, an anti-impact link was designed to improve the algorithm’s robustness, considering the interference caused by other mechanical equipment during the control process. The influence of abnormal error signals in the control weight coefficient correction term was suppressed, and a percentage function was introduced to limit the output signal. Finally, the feasibility and effectiveness of the DMFxLMS algorithm were verified through simulations and experiments. The results demonstrated that the DMFxLMS algorithm achieved significant control effects for both constant frequency line spectrum excitation and frequency fluctuating line spectrum excitation, fulfilling the objective of reducing base vibration. The DMFxLMS algorithm exhibited fast convergence and excellent robustness, making it suitable for practical engineering applications.

In biological systems, nanobubbles (NBs) effectively enhance hydrogen molecule retention and scavenging reactive oxygen species (ROS), but the underlying mechanisms remain elusive. To investigate this, we prepared hydrogen NB water samples with consistent dissolved hydrogen levels but varying NB densities to explore their physicochemical properties and effects on green algae (Chlorella vulgaris) under oxidative stress induced by copper ions (Cu2+) and cadmium ions (Cd2+). The results indicated a strong correlation between the hydrogen NB number density and the 25 % inhibitory concentration of Cu2+ over 24 h, with ROS removal efficiency increased with the NB number density. Gas chromatography showed that the hydrogen NBs in the solution had a high gas density that enhanced hydrogen transport into C. vulgaris. With regard to mitochondrial activity, hydrogen NBs were observed to enhance the function of mitochondrial complexes I and V and increase the mitochondrial membrane potential. Experiments with C. vulgaris mitochondrial electrodes showed that the electron transfer rates increased significantly in the presence of hydrogen NBs. We concluded that the high gas density of hydrogen NBs augments intracellular hydrogen delivery and strengthens mitochondrial functions.

Abstract Facing the global challenge of water scarcity, solar‐driven desalination is considered a sustainable technology for obtaining freshwater from seawater. However, issues such as uncontrolled salt crystallization and bacterial contamination limit its efficiency and practicality. This study proposes an innovative solar‐driven evaporator designed to address these challenges using optimized shape design and advanced photothermal materials. Based on finite element analyses, cylindrical evaporators with a “Starburst Turbine” shape are designed and fabricated, achieving directional salt crystallization and a record‐breaking water collection rate of 3.56 kg m−2 h−1 and an evaporation rate of 4.57 kg m−2 h−1 under one sun illumination. During continuous 60‐h illumination tests, the evaporator maintained a stable evaporation rate, attributed to its excellent directional salt crystallization capability. Additionally, the evaporator demonstrates superior photodynamic antibacterial performance and photocatalytic degradation of organic pollutants. Under one sun illumination for 1 h, it achieves 100% sterilization of S. aureus and E. coli, and a 95.4% degradation of methylene blue (MB), demonstrating its potential to purify various wastewater types. These findings underscore the significant scientific and practical value of integrating antibacterial and photocatalytic functions into solar water purification materials, providing a sustainable solution to global water scarcity challenges and environmental protection.

Abstract A large‐scale apparent polar wander occurred during the Jurassic interval, which is interpreted as true polar wander (TPW). As the motion is nearly orthogonal to the TPW axis, the North China Block (NCB) experienced the largest latitudinal and environmental changes and provides unique constraints on Jurassic TPW. However, due to the lack and uneven quality of paleomagnetic data, TPW records in North China are controversial. Here, we report a new paleomagnetic pole (80.8°N, 13.0°E, A95 = 7.4°) from the late Jurassic sills and dykes that intrude the Nandaling and Xiahuayuan formations in the NCB. The new pole places the NCB at 36.8° ± 7.4°N at 155 ± 3.4 Ma, using Beijing as the reference site. Combined with the reliable Jurassic poles, our study reveals a large, steady southward shift of 37.3° ± 7.2° for the NCB during the Middle and Late Jurassic, and reflects a component of TPW. The position of ∼155 Ma pole also supports significant TPW prior to ∼160 Ma and agrees with proposals attributing the diachronous 165–155 Ma aridification across the Eastern Asian blocks.

IntroductionDue to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.Materials and MethodsThe potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.ResultsA total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DiscussionThe findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.

Abstract Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3’s role in CKD’s narrative and position it as a promising therapeutic contender.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010–2019. The burdens of five categories of disease causes – cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases – were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Abstract Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective studies is limited. Here, we analyze data of 352,277 participants from UK Biobank with 12.25-year follow-up. Compared with non-frail individuals, pre-frail and frail individuals have increased risk for incident depression independent of many putative confounds. Altogether, pre-frail and frail individuals account for 20.58% and 13.16% of depression cases by population attributable fraction analyses. Higher risks are observed in males and individuals younger than 65 years than their counterparts. Mendelian randomization analyses support a potential causal effect of frailty on depression. Associations are also observed between inflammatory markers, brain volumes, and incident depression. Moreover, these regional brain volumes and three inflammatory markers—C-reactive protein, neutrophils, and leukocytes—significantly mediate associations between frailty and depression. Given the scarcity of curative treatment for depression and the high disease burden, identifying potential modifiable risk factors of depression, such as frailty, is needed.

Abstract Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = − 0.48, 95% CI (− 0.69, − 0.27), Z = 4.54, P

Abstract Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.

Wind power generation has become an indispensable part of the power supply side of the power grid. Due to the intermittent and uncertain characteristics of wind energy, short-term wind power prediction plays an important role in the stable operation of power system. By constructing the digital twin model, real-time and high-precision prediction of wind energy is realized. First, the genetic algorithm-support vector machine (GA-SVM) algorithm is used to build the model. Multidimensional sensors and meteorological stations of the virtual wind power generation system collected the meteorological data of the environment and updated the meteorological history database at the same time. Second, based on the collected meteorological data, the preliminary prediction results are obtained, and by searching in the historical database, the predicted value and the actual output value of wind turbines or wind farms under similar conditions are obtained. Finally, the prediction results of the GA-SVM are modified to obtain the predicted value of the digital twin model. The prediction method can greatly improve the accuracy of the short-term forecast of wind energy.

Abstract Background Chronic back pain affected 619 million people globally in 2020 which accounts for a heavy disease burden causing tremendous productivity losses. Current therapies including ibuprofen, duloxetine, and opioids might cause side effects and even severe drug use disorders. Therefore, a non‐pharmacologic therapy with better or equivalent efficacy and fewer side effects is needed. Methods We did a multi‐center, single‐blinded, randomized, positive drug controlled, clinical trial. Patients with chronic back pain in moderate severity were randomized into receiving hot stone massage or flurbiprofen plaster group. Both interventions were 2 weeks with a follow‐up of 4 weeks. The primary outcome was the change in the score of the Global Pain Scale (GPS) from baseline to week 2. Secondary outcomes included Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Pain Self‐Efficacy Questionnaire (PSEQ), Hospital Anxiety and Depression Scale (HADS), and Short Form‐36 (SF36) from baseline to week 2 and week 6. Exploratory outcome assessment included the muscle thickness measured by ultrasound. Any adverse event was monitored throughout the study period. Results A total of 120 patients were enrolled in this trial. At 2 weeks GPS decreased significantly in the hot stone massage group compared to the flurbiprofen group (difference between groups = ‐8.1 points, 95% confidence interval [CI] ‐15.8 to ‐0.3, p = 0.047). Moreover, hot stone massage also showed more improvement at 2 weeks compared to flurbiprofen, including NRS (‐0.5 points, 95% CI ‐1.0 to ‐0.1, p = 0.029), PSEQ (5.4 points, 95% CI 0.5 to 10.2, p = 0.030), and mental component of Short Form‐36 (SF‐36) (1.7 points, 95% CI 0.4 to 2.9, p = 0.010), but not in CPAQ (p = 0.131), HADS (p = 0.303 for depression, p = 0.399 for anxiety), or SF‐36 (p = 0.129 for physical component, p = 0.246 for social component, p = 0.076 for fatigue component). A total of two participants in the hot stone massage group reported mild pain on skin surface when receiving the procedure at the first intervention session.

Background: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. Methods: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. Results: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P

Abstract Current global climate models (GCMs), limited to grid‐scale land‐atmosphere coupling, cannot represent subgrid urban‐rural precipitation contrasts. This study develops an innovative two‐way subgrid land‐atmosphere coupling framework in the National Center for Atmospheric Research (NCAR) Community Earth System Model version 2 (CESM2) to explicitly resolve land‐atmosphere interaction over subgrid individual land units. Results show that urban heat island (UHI) leads to the urban rainfall effect (URE), which in turn alleviates overestimated UHI over China in CESM2. The URE manifests as a shift toward more heavy precipitation and less light precipitation in world urban areas than in surrounding rural counterparts. This feature is consistent with available observations. In heavy precipitation situations, the UHI promotes atmospheric instability and enhances atmospheric water vapor holding capacity, resulting in more heavy precipitation in urban areas. Conversely, in light precipitation situations, the UHI and decreased evaporation from urban impermeable surfaces diminish atmospheric relative humidity, suppressing light precipitation.

Increasing the utilisation rate of waste glass in asphalt mixtures, especially that with a wide range of particle sizes, is of great importance to resource recycling, while it may bring drawbacks to the engineering performance of asphalt mixtures. Incorporating polyurethane (PU) as a modifier can enhance asphalt mixture's performance, but there is limited research considering the usage of waste glass as aggregates. In this study, PU modified asphalt mixtures were prepared, incorporating waste glass particles ranging in size from 2.36 mm to 9.5 mm as a portion of the aggregates. Optimal preparation methods and mix designs for the PU-modified asphalt binder were determined through a series of tests designed based on Orthogonal method. The performances of the PU-modified asphalt binders were then evaluated to guide the selection of the optimal preparation method and mix design. PU-modified waste glass asphalt mixtures were then prepared and their engineering performances were assessed at various glass-to-aggregate ratios. The results show that scheme PU-1 with a shearing temperature of 140°C, a shearing time of 10 min, a PU content of 10% and a compatibiliser content of 2% is suggested for preparing the PU-modified asphalt binder, which shows the best performances due to superior chemical modification and compatibility. Higher glass content decreases the high/low-temperature performance, but it can be improved by adding silane coupling agent or hydrated lime, with the latter showing better results. The incorporation of glass particles has little impact on anti-sliding performance, and asphalt mixtures maintain excellent anti-sliding properties up to a 20% replacement rate. Overall, the performance of the asphalt with waste glass up to 15% can meet the specification requirements. This novel approach offers a potential solution to enhance the incorporation of waste materials in asphalt construction, contributing to sustainable and environmentally-friendly road construction.