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Lin Zhang, Shou-Ying Du, Yang Lu, Chang Liu, Zhi-Hao Tian, Chang Yang, Hui-Chao Wu, Zhen Wang School of Chinese Materia Medica, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Abstract: Nasal administration is a high-potential delivery system, particularly because it can provide a pathway from the nose to the brain. The objective of this research is to characterize puerarin transport across a Calu-3 cell monolayer used as a model of the nasal mucosa and to evaluate the influence of puerarin in combination with paeoniflorin and menthol to explore the enhanced mechanism of the permeability at the cell level. The apparent permeability coefficients (Papp) of puerarin bidirectional transport were both 0.05). However, the addition of menthol significantly (P

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Abstract Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC. Graphical Abstract

[Objective] The objective of this study was to analyze the spatial distribution characteristics of surface soil moisture content in the rocky desertification slope under different land preparation measures and to provide references for improving water resources utilization efficiency and agricultural management level on rocky desertification slopes. [Methods] The citrus forest under three land preparation measures of reverse slope, flat terrace, and natural slope on rocky desertification slope were chosen as the research objects. Classical statistics, geostatistics and multifractal theory were used to analyze the spatial distribution characteristics of soil moisture content. [Results] (1) The soil moisture content of the reverse slope was significantly higher than that of the flat terrace and the natural slope (p

N-linked glycosylation is a common posttranslational modification of proteins that results in macroheterogeneity of the modification site. However, unlike simpler modifications, N-glycosylation introduces an additional layer of complexity with tens of thousands of possible structures arising from various dimensions, including different monosaccharide compositions, sequence structures, linking structures, isomerism, and three-dimensional conformations. This results in additional microheterogeneity of the modification site of N-glycosylation, i.e., the same N-glycosylation site can be modified with different glycans with a certain stoichiometric ratio. N-glycosylation regulates the structure and function of N-glycoproteins in a site- and structure-specific manner, and differential expression of N-glycosylation under disease conditions needs to be characterized through site- and structure-specific quantitative analysis. Numerous advanced methods ranging from sample preparation to mass spectrum analysis have been developed to distinguish N-glycan structures. Chemical derivatization of monosaccharides, online liquid chromatography separation and ion mobility spectrometry enable the physical differentiation of samples. Tandem mass spectrometry further analyzes the macro/microheterogeneity of intact N-glycopeptides through the analysis of fragment ions. Moreover, the development of search engines and AI-based software has enhanced our understanding of the dissociation patterns of intact N-glycopeptides and the clinical significance of differentially expressed intact N-glycopeptides. With the help of these modern methods, structure-specific N-glycoproteomics has become an important tool with extensive applications in the biomedical field.

Abstract The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry–Perot resonator. The separated gain medium enhances the threshold difference by 36-fold between nucleolus and its surroundings, enabling selective laser emissions at nucleolar area while maintaining lower-order mode. The laser emission image provides insights into structural inhomogeneity, temporal fluid-like dynamics, and pathological application. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the label-free flow cytometry for nucleolus. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.

Abstract TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson’s disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5’-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment. α-Methylene-γ-butyrolactone (α-M-γ-B) is a core moiety that widely exists in natural SLs. This study was designed to investigate the anti-arthritic potential of α-M-γ-B as an independent small molecule in vitro and in vivo. α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs. α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages. The transcriptome sequencing suggested that α-M-γ-B regulated the immune system pathway. Consistently, α-M-γ-B attenuated collagen type II-induced arthritic (CIA) phenotype, restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice. Mechanistically, although α-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65, which blocked the activation of NF-κB. Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis. α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela. In conclusion, α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability. These results suggest that α-M-γ-B has the potential to serve as an alternative candidate for treating RA. The greater electrophilicity of α-M-γ-B, the basis for triggering strong anti-inflammatory activity, accounts for the reason why α-M-γ-B is evolutionarily conserved in the SLs by medical plants.

In the process of coal mining, a large amount of respirable dust is generated, which seriously endangers the miners’ health. As the most widely used dust reduction technology, the spray technology has the advantages of high efficiency and cleanliness, but the existing spray technology does not have a strong ability to capture respirable dust, and the atomization efficiency is low. In order to solve those problems, the supersonic coaxial aerodynamic atomization technology was developed. The atomization characteristics of the technology were studied by experimental and numerical simulations, and the dust reduction characteristics of supersonic water drawing siphon aerodynamic atomization and supersonic coaxial atomization were compared based on the self-designed dust reduction experimental platform. At the same time, the dust separation experiment of the two technologies revealed the sedimentation mechanism of dust under the action of supersonic dynamic micro-fog curtain. The results show that under different aerodynamic pressures, the coaxial probe water injection method adopted by the supersonic coaxial atomization dust reduction device greatly reduces the energy loss of the probe structure on the supersonic flow field, significantly improves the atomization efficiency, and produces a large number of high-speed droplets below 11 μm with an uniform spatial distribution, and the particle size is reduced by 12%−50% compared with the siphon atomization device, forming a large-scale high-speed fine fog area in the spray flow field. The coupling effect of the droplet field and the dust field can be characterized by the instantaneous dispersion of the dust and determined by the distribution characteristics of the droplet field. At different times, the variation trend of the graded dust reduction efficiency in each particle size interval is different, and the contribution to the total dust reduction efficiency under different pressures is also different. The large-scale high-speed fine mist generated by the supersonic coaxial atomization technology is easy to capture respirable dust, and the classification efficiency of PM0−PM2.5 is more than 75%, and the maximum is 90%. The increase of pressure enlarges the range of high-speed fine mist, which is conducive to the capture of fine particles. During the confined space migration of dust-containing airflow, the sedimentation process of dust under the action of supersonic dynamic micro-fog curtain can be divided into droplet dust capture area, condensation and sedimentation area, and evaporation escape area. The different behaviors and concentration distributions of fog droplets and dust in different regions are the results of the drag migration of spray airflow and airborne wind flow, the capture of high-speed micro-fog collision, the condensation and settlement of fog droplets, and the weight loss of fog droplet evaporation.

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

In the past few years, there have been many breakthroughs in the treatment of heart failure, especially in drug therapy. The classification of chronic heart failure and treatment methods for heart failure and its complications are also constantly updated. In order to apply these achievements to a better diagnosis and treatment of heart failure patients in China, Chinese Society of Cardiology, Chinese Medical Association, Chinese College of Cardiovascular Physician, Chinese Heart Failure Association of Chinese Medical Doctor Association, Editorial Board of Chinese Journal of Cardiology have jointly published the Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2024, which comprehensively updates the new consensus and evidence-based treatment in the field of heart failure. These contents are of great significance for guiding diagnosis and treatment of heart failure patients in clinical practice. This article, therefore, aims to interpret the main updated contents and key points to provide readers with a better understanding of its key information.

The increasing consumption of paper products has led to a shortage of paper fiber raw materials. It is necessary to develop new plant materials to alleviate the shortage of fiber suitable for papermaking. In this study, the fast-growing plant golden bamboo grass (Arundo donax), which is cultivated and planted in Guangxi province of China, was used as a new material for pulping. The average pulp yield by cyclic-cooking method averaged 48.6%, being 4.1% greater than the pulp yield by the ordinary caustic soda method. Much of the increased yield was attributable to the reprecipitation of lignin onto the fibers. The paper properties of the pulp prepared by cycle-cooked method did not decrease significantly, compared with the pulp prepared by the usual single-cooked method. Therefore, the pulp met the requirements of national standards of many kinds of papers. However, the pulp was not suitable for bleaching, due to its high consumption of oxidizing agents to reach the required brightness. Therefore, this research demonstrates that the fast-growing plant, Arundo donax is a good raw material for pulp, and the innovative method of cycle-cooking method can significantly improve the pulp yield.

Abstract The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

Studying the variation characteristics and main influencing factors of PM2.5 concentration in the Yangtze River Basin from 2016 to 2021 could provide references for optimizing the policy of collaborative governance of the atmospheric environment in the basin. Using the PM2.5 concentration data from 110 national stations in the Yangtze River Basin from 2016 to 2021, the temporal and spatial variation characteristics of PM2.5 were analyzed with the Theil-Sen trend analysis and Mann-Kendall statistical test methods. Combined with the Environmental Meteorological Assessment Index (EMI), the relative contributions of the two main influencing factors including the meteorological conditions and emission reduction measures, to the changes in PM2.5 concentration changes during the "13th Five-Year Plan" period (2016—2020) and the first year of the "14th Five-Year Plan" (2021) were quantitatively analyzed. The results were as follows. (1) Significant spatial variations in PM2.5 concentration distribution were found in the Yangtze River Basin was uneven in 2016-2021. The high-value areas were in the eastern part of the Hanjiang River Basin extending southward to the eastern part of the Dongting Lake Basin and the southern part of the Mintuo River, While the low-value area was in the upper and middle reaches of the Jinsha River Basin. (2) During the "13th Five-Year Plan" period, PM2.5 concentration in major cities of the Yangtze River Basin decreased year by year, with an annual variation rate of -3.62μg·m-3·a-1. However, PM2.5 concentration about 40% of the Yangtze River Basin region increased in 2021, which was mainly distributed in the upper reaches of the Yangtze River Basin and Dongting Lake Basin. (3) The PM2.5 in the western part of the basin was greatly affected by meteorological conditions, while the eastern part was greatly affected by emission sources and other factors. (4) Meteorological conditions and emission reduction measures during the "13th Five-Year Plan" period were conducive to the decrease of PM2.5 concentration.Their contribution rates to the increase of PM2.5 were -16.54% and -14.00%, respectively. Compared with the previous year, the emission reduction measures in 2021 were generally beneficial to the decrease of PM2.5 concentration (contribution rate of -5.84%), but adverse meteorological conditions (contribution rate of 4.49 %) offset part of the emission reduction effects, making a slight decrease in the PM2.5 concentration.

Abstract As the severity of global climate change escalates, carbon peak and carbon neutrality have emerged as international imperatives. Green taxation, a crucial fiscal strategy promoting the transition to a green low-carbon economy, demands thorough investigation regarding its efficacy and operational mechanisms. Predominantly, existing research has concentrated on the macroeconomic implications of green taxes, while their influence on regional green growth and innovation remains underexplored. This paper delineates green taxation in both a broad and narrow sense, elucidating its essence and potential in stimulating regional green progress and innovation. Utilizing panel data from 30 provinces in China spanning 2004 to 2021, a bidirectional fixed-effects model was developed for empirical analysis. Moreover, an impact mechanism model was constructed to delve into how green taxation specifically affects regional green development and innovation. Findings reveal that green taxation significantly fosters regional green growth and markedly enhances green innovation. Nonetheless, due to the resource crowding-out effect, it adversely impacts the comprehensive innovation capabilities of regional enterprises. This insight offers a fresh perspective on the paradoxical effects of green taxation, underscoring the necessity for a balanced approach in policy design and implementation. Drawing on these conclusions, the paper presents tailored policy recommendations.

Abstract Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.

It is known that load forecasting plays an important role for the smart grids and mostly, the users have the combinational load forecast demands with different time-scales. However, due to various internal or external factors, such as poor management, the available load data set is limited. Therefore, the problem becomes as the high-precision combinational load forecast at different time-scales but with limited valid datasets. In this paper, taking the work in a city power company of China as an example, an empirical study for this problem is considered and then a robust forecasting system is built. The forecasting models are designed and screened and then constructed a model library for the system. In order to improve the robustness of the designed system, a mean absolute percentage error (MAPE) based dynamic model selection method is proposed and finally the performance of the system is verified on the State Grid Chongqing Company of China. The results indicate that our designed multi-temporal-spatial-scales load forecast system can dynamically select the best model for different demands, which demonstrates that the build system is an effective and reliable system-level solution. In particular, for the annual based load forecast, 80% of the industries in the considered city have a MAPE less than 5%, while the MAPE of the whole city is less than 2.160%; for the monthly based load forecast, 87% of the industries in the considered city have a MAPE less than 10%, while the MAPE for the whole city is less than 3.755%. In addition, for the annual based forecast, GM(1,1) is mostly used for the industry-based forecasts, but the model with the highest average forecast accuracy is LR-ER. While for region-based forecasts, the mostly selected models are GM(1,n) and AR. For the monthly based forecast, GM(1,1)-SI and FOA-HW have a higher average accuracy than other models for both industries- and region-based forecasts, respectively.

Abstract Utilizing data that encompass municipalities and regions within China at the prefectural level and beyond, spanning the period from 2012 to 2021, this study employed the spatial Durbin model to assess the spatial spillover impact of the digital economy in propelling low-carbon advancement within regional physical industries. This investigation elucidates the spatial spillover mechanism that underlies the low-carbon evolution of regional industries catalyzed by the digital economy and offers nuanced insights. The findings delineate the following observations: (1) The digital economy propels the low-carbon progression of indigenous physical industries and stimulates the low-carbon development of proximate regions’ physical industries through discernible spatial spillover effects. (2) The spatial spillover ramifications of the digital economy manifest a substantive correlation with urban attributes, including geographical positioning, population size, and market integration levels. Notably, municipalities situated in the southeast coastal region, those characterized by larger population sizes, and those exhibiting heightened market integration levels show greater spatial spillover effects attributable to the digital economy. (3) The safeguarding of intangible asset equity property, a pivotal institutional underpinning for fostering digital economic development, amplifies the spatial spillover effect of the digital economy in propelling low-carbon development within regional industries. (4) As geographical and spatial distances expand, the spatial spillover effect of the digital economy attenuates, indicating a diminishing influence with increasing spatial separation.

Abstract To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593–0.9996) in the training cohort and 0.909 (95% CI 0.7921–1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

Abstract Distributed energy systems encompass a diverse range of generation and storage solutions on the user side, where decentralized management schemes to maximize the overall social welfare are preferred considering their dispersed ownership. However, either security or privacy problems occur in recently proposed schemes. Here we report a decentralized framework leveraging the strengths of blockchain and parallelizable mathematical algorithms to overcome these potential drawbacks. The system owners bid cost functions and operating constraints through masked but coupled management subproblems, which are redistributed by the blockchain to be verifiably solved by competent peers. Such processes are iteratively executed as decisions and shadow prices are exchanged among participants, until an equilibrium is reached. The interactive framework ensures decentralized, privacy-preserving, and secure management of multiple energy sources, and reduces the total cost by 3.0 ~ 7.5% in the test system. Our results benefit the energy prosumers and promote a more active and competitive power grid.

Background Gut microbiota is closely related to the occurrence and development of diabetes and affects the prognosis of diabetic complications, and the underlying mechanisms are only partially understood. We aimed to explore the possible link between the gut microbiota and vascular inflammation of diabetic mice. Methods The db/db diabetic and wild-type (WT) mice were used in this study. We profiled gut microbiota and examined the and vascular function in both db/db group and WT group. Gut microbiota was analyzed by 16s rRNA sequencing. Vascular function was examined by ultrasonographic hemodynamics and histological staining. Clostridium butyricum (CB) was orally administered to diabetic mice by intragastric gavage every 2 days for 2 consecutive months. Reactive oxygen species (ROS) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by fluorescence microscopy. The mRNA expression of inflammatory cytokines was tested by quantitative polymerase chain reaction. Results Compared with WT mice, CB abundance was significantly decreased in the gut of db/db mice, together with compromised vascular function and activated inflammation in the arterial tissue. Meanwhile, ROS in the vascular tissue of db/db mice was also significantly increased. Oral administration of CB restored the protective microbiota, and protected the vascular function in the db/db mice via activating the Nrf2/HO-1 pathway. Conclusion This study identified the potential link between decreased CB abundance in gut microbiota and vascular inflammation in diabetes. Therapeutic delivery of CB by gut transplantation alleviates the vascular lesions of diabetes mellitus by activating the Nrf2/HO-1 pathway.

The Al–Zn–Mg–Cu 7055 aluminum alloy was meticulously fabricated through spray forming (SF) technology, followed by hot extrusion and T76 treatment. This comprehensive process allowed for a thorough investigation of its microstructural characteristics, mechanical properties, and fatigue behavior. Post-treatment analysis revealed that the SF-7055 aluminum alloy exhibited no notable segregation or porosity defects, ensuring its exceptional quality and reliability. The microstructural analysis revealed a uniform distribution of refined grains and dispersed precipitates, contributing to the material's strength. Mechanical testing demonstrated that the hot extruded SF-7055 aluminum alloy exhibits superior tensile strength and elongation, with significant anisotropy in mechanical properties favoring the extrusion direction (ED) over the transverse direction (TD). Fatigue testing under varying cyclic stresses revealed an extended fatigue life in the ED-oriented specimens, attributed to the texture-induced resistance to crack initiation and propagation. The study underscores the effectiveness of SF and hot extrusion in enhancing the SF-7055 aluminum alloy's performance, making it a viable candidate for critical aerospace applications. The findings provide valuable insights into the relationship between processing, microstructure, and properties, offering a pathway to the design and fabrication of high-performance aluminum alloys.

To address the issues of shrinkage cracking, high energy consumption and high carbon emission of traditional cement-based sealing materials, the authors investigated the use of sodium alginate (SA) crosslinking metal ions to prepare SA modified alkali activated waste incineration base ash (MSWI-BA) -granulation blast furnace slag (GBFS) based gaging plugging material (SWM). The optimal water-solid ratio was determined by evaluating compressive strength and setting time to be 0.4. The influence of SA modification on the high temperature resistance of the gelling material was investigated by analyzing the compressive strength, shrinkage rate, and fracture morphology of the gelling material at different temperatures. The results showed that after SA modification, the high temperature resistance improved, the surface cracks on the modified cementable material were significantly reduced after heating, and the shrinkage rate was reduced by 26.5% compared to that before modification. The residual compressive strength is still as high as 17.25 MPa after heating at 400 ℃. Combined with microscopic morphology, pore structure properties, and thermal analysis experiments, the generation mechanism of SA modified gelling material was examined. The results revealed that the SA modified MSWI-BA-GBFS based gelling material refines pore size and reduces pore volume via coordination crosslinking of SA and Ca2+/Al3+ and the synergistic effect of the silico-aluminate covalent network, thus maintaining the matrix structure's integrity after heating, improving cracking properties. The simulation findings suggest that the leakage plugging performance of SA modified MSWI-BA-GBFS based gelling material with water solid ratio 0.4 is superior to that of mining cement-based material, demonstrating a better leakage plugging performance. The development of SA modified MSWI-BA-GBFS based gelling plugging material not only provides an effective way for the resource utilization of municipal waste incineration bottom ash, but also provides a type of environmental protection fire-fighting material with high compressive strength, anti-shrinkage cracking, and high temperature resistance, which can completely replace the traditional mine cement based plugging material.

Abstract Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. Case presentation This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. Conclusions In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Abstract Background Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. Results In this study, we found that diabetic ApoE–/– mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE–/– mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. Conclusions Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE–/– mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach. Graphic Abstract

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

IntroductionDiarrhea is a common clinical condition that can potentially be fatal. Current treatment options often have side effects, such as constipation and vomiting, and there remains a need for more effective therapies. Pickled vegetables, a famous traditional food in China, have been suggested in clinical studies to alleviate diarrhea in children, particularly through the use of pickle water (PW). However, the pharmacological effects and mechanisms of PW on intestinal health remain unclear. This study aimed to explore the protective effects of PW on castor oil-induced diarrhea in ICR mice and to investigate its potential mechanisms.MethodsTo evaluate the antidiarrheal effects of PW, we used a castor oil-induced diarrhea model in ICR mice. Various indices were measured to assess the severity of diarrhea. After euthanizing the mice, oxidative stress markers in the ileum were assessed using biochemical methods, and the expression of tight junction-related proteins in the ileum was analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora.ResultsThe results showed that PW supplementation reduced body weight without significantly affecting organ index and liver function in the castor oil-induced diarrhea mice. PW also effectively reduced the dilution rate, diarrhea index, average loose stool grade, propelling distance of carbon powder, and intestinal propulsive rate while improving the pathological abnormality in the ileum. Furthermore, PW enhanced the activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) while reducing malonaldehyde (MDA) levels. PW also increased the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin in the ileum. Additionally, the analysis of 16S rDNA revealed that PW increased both α and β diversity, improved the composition of the intestinal flora, and restored it to a normal level.DiscussionCollectively, dietary PW administration ameliorates Castor oil-induced diarrhea by restoring tight junctions between intestinal mucosal cells, suppressing oxidative stress, and regulating the composition of intestinal flora. These findings suggest that PW may be a promising strategy for managing diarrhea.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

Hidden champions are SMEs with strong global competitiveness in specialized fields but low profile. China’s hidden champions show less internationalization compared to their global peers, despite niche market dominance. Consequently, an exploration of the internationalization trajectories and determinants for China’s hidden champions is essential. This study utilizes fsQCA to investigate the internationalization strategies of 91 hidden champions, from China, using the “Efficiency-Structure-Environment” analytical framework. Five principal causal pathways for international operations are illustrated, categorized into three main driving models: “Efficiency-Environment,”“Efficiency-Structure,” and “System Interaction,” with the first model being the most dominant. The study further classifies hidden champions by ownership, finding that both state-owned and private enterprises predominantly follow the “Efficiency-Structure” driving model. Additionally, when classified by certification types, all categories are found to align with the “System Integration” model. Notably, the international path for cultivation hidden champions is also well-explained by the “Efficiency Dominance” model. Lastly, the study delineates industry-specific models: general equipment manufacturers employ the “Efficiency-Structure” model, special equipment manufacturers use the “Structure-Environment” model, and the computer industry follows the “System Integration” model.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the outbreak of COVID-19 in Wuhan, China. As a highly infectious epidemic, SARS-CoV-2 rapidly evolves. Presently, COVID-19 coexists with humans, mainly with mild or moderate disease. The latest Guidelines for the Diagnosis and Treatment of COVID-19 (trial version of the 10th Edition) recommend several oral traditional Chinese medicines (TCMs) for treatment. This study aims to evaluate the evidence-based benefits of these TCMs as adjunctive therapies to conventional western medicine (CWM) for patients with mild or moderate COVID-19. Methods: We conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the PRISMA checklist. We searched PubMed, Cochrane Library, Embase, CNKI, and Wan-Fang databases to retrieve randomized controlled trials and retrospective cohort studies of TCM in combination with CWM on the treatment of mild or moderate COVID-19 that were published as of December 25, 2023. A network meta-analysis using the frequency model was employed to evaluate the benefits of different interventions. Results: A total of 30 eligible studies, enrolling 4144 participants, utilized 7 marketed oral TCMs in China. Compared with CWM alone, the integration of TCMs with CWM can significantly reduce severe conversion rate. This combined approach also enhances the clinical effective rate, shortens the negative conversion time of nucleic acid, and improves both symptoms and blood biochemical markers in patients. The network meta-analysis provided preliminary evidence of the superiority of specific TCMs for various outcomes: Qingfei Paidu for raising the CT improvement rate and clinical effective rate, and shortening the negative conversion time of nucleic acid; Huashi Baidu for reducing severe conversion and improving cough; Xuanfei Baidu for improving fatigue; Jinhua Qinggan for improving fever; Lianhua Qingwen for shortening the recovery time of fatigue and cough; and Shufeng Jiedu for shortening the recovery time of fever. Conclusions: TCM in combination with CWM may be beneficial for patients with mild or moderate COVID-19. Each TCM may have distinct benefits in COVID-19.

Objectives: Individuals diagnosed with schizophrenia have a high incidence and fatality rates due to pneumonia. Sarcopenia is a contributing factor to the development of pneumonia in patients with schizophrenia. In this study, we examine the effectiveness of three simple screening questionnaires, namely SARC-F, SARC-CalF, and SARC-F + EBM, in predicting the occurrence of pneumonia in stable patients with schizophrenia who are experiencing sarcopenia. Design: A prospective study. Setting: Patients with stable schizophrenia patients aged ≥50 years in two psychiatric hospitals in western China. Methods: Medical data from patients were collected from September 1 to September 30, 2020. Data specifically from patients diagnosed with pneumonia were collected for a period of one year, from October 2020 to October 2021. Three hundred thirty-five stable schizophrenia patients, among whom 229 were males (68.36 %.), were enrolled in the prospective study. The risk of sarcopenia was evaluated using the SARC-F, SARC-CalF, and SARC-F + EBM scores, with values of ≥4, 11, and 12 indicating an elevated risk of sarcopenia. The collected data were analyzed using logistic regression analysis to establish the association between the scores of these screening tools and the risk of pneumonia in individuals with stable schizophrenia. Results: The rate of pneumonia in stable schizophrenia individuals was 24.48 %. Among the included stable schizophrenia patients, the incidence of pneumonia in individuals with SARC-CalF scores ≥11 was higher than in those with SARC-CalF scores less than 11 (29.91 % vs 14.88 %, P = 0.002). In individuals with SARC-F + EBM scores ≥12, the pneumonia occurrence was higher than that in those with SARC-F + EBM scores less than 12 (37.33 % vs 20.77 %, P = 0.003). However, this pattern was not found in patients with stable schizophrenia who had SARC-F scores of 4 or above and less than 4. Following the implementation of logistic regression data analysis, it has been discovered that persons with SARC-CalF scores greater than or equal to 11 were at a significantly increased risk of having pneumonia compared to patients with SARC-CalF scores less than 11 (OR = 2.441, 95 % CI: 1.367–4.36). After adjusting the possible confounders, patients with SARC-CalF scores ≥11 had a greater danger of pneumonia (OR = 2.518, 95%CI: 1.36–4.665). As a result, it was found that individuals with SACR-F+EBM scores ≥12 were more likely to acquire pneumonia (OR = 2.273, 95%CI: 1.304–3.961) when compared to those with scores

BackgroundReactor core computational fluid dynamics (CFD) plays a crucial role in identifying core vulnerabilities, optimizing feature structures, and improving safety and economic in nuclear reactors. However, conventional pressurized water reactor fuel assemblies often feature a multitude of spacer grids with mixing vanes, leading to challenges in mesh generation and numerical solution instability, excessive computational resource requirements. The current momentum source model established on the basis of the mechanism of fluid-structure interaction has not considered the effect of the low-pressure region on the fluid downstream of the mixing vanes, leading to significant errors in predicting the axial flow distribution downstream of the mixing vanes. Furthermore, it is challenging to identify the solid domain of the mixing vanes and to add momentum source terms.PurposeThis study aims to present a joint simulation scheme based on detailed porous media and momentum source modeling to simulate coolant flow in 5×5 rod bundle channels with mixing vanes, hence to reduce cells, lower mesh generation difficulty, and enhance numerical stability during the CFD solving process.MethodsThis scheme employed a detailed porous media approach in the spacer zone, while adopting Global Momentum Source Model in the vane zone. Simultaneously, a domain identification scheme was developed to determine the placement of momentum sources and detailed porous media models. The position of mixing vanes within the fluid domain was accurately located by this approach and established detailed porous media and momentum source models based on the fluid-structure interactions in the grid spacer zone and leeward side and windward side of mixing vanes. To simulate the flow field distribution within the spacer zone, a detailed porous media model was employed to enhance local flow resistance, thereby achieving an accurate simulation of the flow field distribution in the spacer zone. Finally, validation against experimental and body-fitted mesh simulations was performed to examine the effectiveness of this scheme in simulating flow blockage, fluid flow, mixing, and vortex shedding.ResultsThis scheme, compared to the momentum source scheme, exhibits stronger numerical stability. In the vane zone, the established momentum source model simultaneously considers the effects of the leeward side and the windward side of mixing vanes, leading to a more accurate prediction of axial flow velocity and heat transfer downstream of the mixing vanes. This approach allows for modeling without needing to consider the structure of the spacer grids with mixing vanes, thus greatly simplifying mesh generation. It achieves complete structured mesh modeling, significantly reducing the number of cells, and enhancing computational efficiency. Validation confirm the effectiveness of this scheme and results in a 90% reduction in cells and a 60% decrease in computational time for modeling and simulation of a 5×5 rod bundle channel with mixing vanes.ConclusionsThis scheme offers simplicity in modeling, reduces CFD computation time, insensitivity to mesh, and superior robustness. Furthermore, when identifying larger-scale components, the approach involves identifying the multi-span fuel components, since the mixing vanes form a regular array in both axial and transverse directions. Therefore, domain identification at a larger scale can be achieved by modifying coordinates, applying momentum source model developed in this paper.

Amid the wave of globalization, the phenomenon of cultural amalgamation has surged in frequency, bringing to the fore the heightened prominence of challenges inherent in cross-cultural communication. To address these challenges, contemporary research has shifted its focus to human–computer dialogue. Especially in the educational paradigm of human–computer dialogue, analysing emotion recognition in user dialogues is particularly important. Accurately identify and understand users’ emotional tendencies and the efficiency and experience of human–computer interaction and play. This study aims to improve the capability of language emotion recognition in human–computer dialogue. It proposes a hybrid model (BCBA) based on bidirectional encoder representations from transformers (BERT), convolutional neural networks (CNN), bidirectional gated recurrent units (BiGRU), and the attention mechanism. This model leverages the BERT model to extract semantic and syntactic features from the text. Simultaneously, it integrates CNN and BiGRU networks to delve deeper into textual features, enhancing the model’s proficiency in nuanced sentiment recognition. Furthermore, by introducing the attention mechanism, the model can assign different weights to words based on their emotional tendencies. This enables it to prioritize words with discernible emotional inclinations for more precise sentiment analysis. The BCBA model has achieved remarkable results in emotion recognition and classification tasks through experimental validation on two datasets. The model has significantly improved both accuracy and F1 scores, with an average accuracy of 0.84 and an average F1 score of 0.8. The confusion matrix analysis reveals a minimal classification error rate for this model. Additionally, as the number of iterations increases, the model’s recall rate stabilizes at approximately 0.7. This accomplishment demonstrates the model’s robust capabilities in semantic understanding and sentiment analysis and showcases its advantages in handling emotional characteristics in language expressions within a cross-cultural context. The BCBA model proposed in this study provides effective technical support for emotion recognition in human–computer dialogue, which is of great significance for building more intelligent and user-friendly human–computer interaction systems. In the future, we will continue to optimize the model’s structure, improve its capability in handling complex emotions and cross-lingual emotion recognition, and explore applying the model to more practical scenarios to further promote the development and application of human–computer dialogue technology.

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

Failure to obtain timely fire services will lead to thermal runaway phenomenon, which will seriously threaten the lives of people and property safety. In this study, a dynamic method was proposed to estimate fire service accessibility based on real-time traffic. To validate the method, a total of 110,055 POls extracted from online maps and existing 12 fire stations in Yiyang were used as fire service demand points and supply points. Travel times of fire trucks from supply points to demand points were calculated based on real-time traffic, and a total of 550,275 valid samples were obtained. The results showed that the ≥10 min fire service coverage rate in Yiyang is only 71.60 %. Based on the distribution area of demand points ≥10 min, the locations of three optimization solutions of new fire stations are proposed. By calculating the total average time (TAT) of the three optimization solutions of proposed new fire stations, it is concluded that TAT decreases by 743.99 s, 99.72 s, 92.59 s, respectively. From perspectives of safety and economy, the construction of the 10 fire stations of optimized solution I will effectively improve the regional fire service level.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Highlights A novel aqueous/aprotic electrolyte with low salt concentration (i.e., 0.5 m Zn(CF3SO3)2+1 m LiTFSI) demonstrated an expanded electrochemical window, which can simultaneously stabilize Zn metal anode and increase the operation voltage of Zn-ion hybrid supercapacitors. The coordination shell of the electrolyte induced by acetonitrile and LiTFSI can not only suppress the Zn corrosion and hydrogen evolution reaction but also promote the cathodic stability and ion migration, which is depicted by the density functional theory simulations together with experimental characterizations. The Zn-ion hybrid supercapacitor based on the developed electrolyte can operate within 0–2.2 V in a wide temperature range with an ultra-long lifespan (> 120,000 cycles).

Abstract Climate change can alter wetland extent and function, but such impacts are perplexing. Here, changes in wetland characteristics over North America from 25° to 53° North are projected under two climate scenarios using a state-of-the-science Earth system model. At the continental scale, annual wetland area decreases by ~10% (6%-14%) under the high emission scenario, but spatiotemporal changes vary, reaching up to ±50%. As the dominant driver of these changes shifts from precipitation to temperature in the higher emission scenario, wetlands undergo substantial drying during summer season when biotic processes peak. The projected disruptions to wetland seasonality cycles imply further impacts on biodiversity in major wetland habitats of upper Mississippi, Southeast Canada, and the Everglades. Furthermore, wetlands are projected to significantly shrink in cold regions due to the increased infiltration as warmer temperature reduces soil ice. The large dependence of the projections on climate change scenarios underscores the importance of emission mitigation to sustaining wetland ecosystems in the future.

Abstract The development of neuromorphic visual systems has recently gained momentum due to their potential in areas such as autonomous vehicles and robotics. However, current machine visual systems based on silicon technology usually contain photosensor arrays, format conversion, memory and processing modules. As a result, the redundant data shuttling between each unit, resulting in large latency and high-power consumption, seriously limits the performance of neuromorphic vision chips. Here, we demonstrate an artificial neural network (ANN) architecture based on an integrated 2D MoS2/Ag nanograting phototransistor array, which can simultaneously sense, pre-process and recognize optical images without latency. The pre-processing function of the device under photoelectric synergy ensures considerable improvement of efficiency and accuracy of subsequent image recognition. The comprehensive performance of the proof-of-concept device demonstrates great potential for machine vision applications in terms of large dynamic range (180 dB), high speed (500 ns) and low energy consumption per spike (2.4 × 10−17 J).

Abstract Background The neural cells in the brains of patients with Parkinson’s disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson’s disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson’s disease based on the central-peripheral-central theory. Methods The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson’s disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. Discussion The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. Trial registration Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Highlights Enhancing rate performance of cellulose-derived hard carbon anodes from the view of cellulose molecular, crystalline, and aggregation structure is explored. Relationship of storage sodium and rate performance according to theoretical calculation and characterization analysis is illustrated. Cellulose intrinsic microstructure, conversion relationship between the allotropes of cellulose, and the critical influences on cellulose-derived carbon structure are discussed.

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8 could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together, these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.

Abstract Objective ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. Research design and methods Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. Results Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. Conclusions PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

Residual stress is an important surface integrity index to evaluate the crack initiation and failure of die surface. The efficient prediction of cutting residual stress can guide the high-quality machining of die and improve its service life. The existing cutting residual stress prediction models are complex, time-consuming and inefficient. In this paper, a hybrid prediction method of cutting residual stress based on finite element-analytical-neural network is proposed. Firstly, the stress, strain and temperature of the cutting surface are obtained based on the orthogonal cutting finite element model. Then, the stress relaxation analytical algorithm considering the elastic-plastic state of the material is used to replace the stress release process of the finite element, and the residual stress distribution data were obtained based on the joint model of finite element and analytical algorithm. Secondly, the surrogate model of BP neural network (SSA-BP) is improved based on SSA algorithm to realize the rapid prediction of characteristic value of residual stress. The effectiveness of the finite element-analytical-neural network hybrid model was verified by the cutting residual stress test of H13 steel. Finally, the effects of tool structure parameters and cutting parameters on the residual stress distribution and the maximum compressive stress and maximum tensile stress of H13 steel were studied. This method can provide a flexible and efficient basic model for obtaining the optimal cutting conditions for controlling the residual stress of H13 steel and other metals.

Objective To observe the effect of Traditional Chinese Medicine nursing technique combined with humanistic nursing intervention in the treatment of elderly patients with insomnia. Methods Totally 80 elderly patients with insomnia were divided into observation group and control group, 40 cases in each group. The control group was given routine nursing, and the observation group was given TCM techniques-auricular acupoint pressing combined with humanistic nursing intervention. The sleep quality was evaluated by Pittsburgh Sleep quality index (PSQI)before and after 2 months of intervention. Results The PSQI score was decreased in both two groups after intervention, and PSQI score in the observation group was lower than that in the control group, with a significant difference(P＜0. 01). Conclusion TCM nursing technique combined with humanistic nursing intervention can effectively improve sleep quality of elderly patients with insomnia (目的 探讨中医特色护理技术联合人文关怀护理干预老年失眠患者的效果观察。方法 选取2019年5月—2020年5月医院收治的80例老年失眠患者为研究对象, 分为观察组与对照组, 各40例。对照组给予常规护理, 观察组在对照组基础上给予中医耳穴贴压联合人文关怀护理。采用匹兹堡睡眠质量指数(PSQI)评估患者干预前及干预2个月后睡眠功能改善情况。结果 干预后, 两组PSQI量表评分均较干预前降低, 且观察组PSQI评分低于观察组, 差异有统计学意义(P＜0. 01)。结论 中医特色护理技术耳穴贴压联合人文关怀护理干预能有效改善老年失眠患者睡眠质量。)

Home-based hospice care for the elderly is an important medical service model aimed at providing comprehensive medical and social support for the elderly. However, due to the special needs and difficulties in nursing of the elderly, a single medical service model often fails to meet their needs. Therefore, establishing a collaborative medical and social worker intervention model for elderly home care and shared care has become an important research direction. This article aims to investigate the sharing model of medical and social workers participating in home-based hospice care under the background of population aging, explore a home-based hospice care model suitable for China's elderly care system, standardize and guide the participation of medical and social workers in home-based shared care, leverage the intervention role of social workers, and meet the needs of patients at home. (老年人居家安宁疗护是一种重要的医疗服务模式, 由于老年人的特殊性和照护难度, 单一的医疗服务模式往往难以满足老年人的需求。因此, 建立医务社工联动介入老年居家安宁疗护共照护理模式成为了一个重要的研究方向。本研究探讨老龄化趋势下医务社工联动参与居家安宁疗护的共照模式, 旨在探索适合我国养老体系下的居家安宁疗护模式, 规范化指引医务社工参与居家共照工作, 发挥社工介入作用, 为老年人提供全面的医疗和社会支持。)

Abstract In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward‐looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.