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Objective To investigate the effect of artesunate (ART) on neuroinflammation in depressed mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway. Methods Mice were divided into model group, control group, low-dose ART group, high-dose ART group, fluoxetine group, and high-dose ART+RocA (cGAS-STING pathway activator) group. Sugar solution consumption experiment and forced swimming experiment were applied to evaluate the depressive behavior of mice; HE staining microscopy was applied to detect pathological changes in hippocampal tissue; ELISA method was applied to detect the level of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), serotonin(5-HT) and dopamine (DA); TUNEL staining microscopy was applied to detect neuronal apoptosis; Western blot was applied to detect Bcl-2 associated X protein (Bax), p53, cGAS, and STING proteins. Results Compared to the control group, the mice in the model group exhibited neuronal pustule degeneration, the sugar water consumption rate, level of 5-HT and DA decreased, the rest time of forced swimming increased. The level of IL-6 and TNF-α, neuronal apoptosis rate, expression of Bax, p53, cGAS, and STING proteins all elevated (P＜0.05); Compared with model group, the damage to hippocampus neurons in the ART low-dose group, ART high-dose group and fluoxetine group neuronal pustular degeneration was alleviated, while sugar water consumption rate, 5-HT, and DA levels increased, the rest time of forced swimming reduced, the level of IL-6 and TNF-α, neuronal apoptosis rate and the expression of Bax, p53, cGAS, and STING proteins reduced (P＜0.05); RocA reversed the improvement effect of high-dose ART on depression in mice. Conclusions ART inhibits neuroinflammation and neuronal apoptosis in depressed mice, and up-regulates amine neurotransmitters expression. The mechanism is potentially related to the blocking of cGAS-STING pathway.

Abstract Background The number of medical research publications by Chinese clinical investigators has risen substantially, contributing to 14.63% of the global total in 2019; however, their tangible impact on clinical decision‐making remains limited. Various evaluation methods have been developed to measure hospital research competence in China, such as Fudan University's China hospital ranking and Science and Technology Evaluation Metrics (STEM) ranking, which predominantly focuses on factors such as academic reputation, volume of publications and patents, and research resources. However, composite indices may not fully capture the actual clinical value generated by medical research. To address this gap, we introduced the “Clinical Influence and Timeliness Evaluation (CITE)” metric to assess both the clinical importance of a given medical research study and the clinical influence of the hospital where it originated. The methodology used relies on the premise that influential medical research would be referenced in clinical guidelines, which serve as critical resources for clinicians. Methods The CITE metric was applied for 78,636 medical studies concerning chronic obstructive pulmonary disease (COPD) published between 2000 and 2020 and referenced in both Chinese and international clinical guidelines for COPD. Specific indexes and formulas were derived to quantify the clinical weight of a medical research study (W) and its timeliness (T), enabling a dynamic assessment of the clinical value of each study and the overall contribution of a particular hospital. Results In this analysis, we incorporated 499 hospitals in China and quantitatively identified their dynamic clinical influence in COPD from 2000 to 2020. Our findings offer objective and targeted evaluation metrics by focusing on clinical relevance and recognizing the collaborative nature of medical research. Conclusion The CITE metric provides an innovative method to gauge the true impact of medical research in China, with potential applications across different medical specialties. CITE can serve as a useful tool for understanding the relationship between research input and practical clinical outcomes, ultimately promoting more clinically relevant research endeavors.

Pulse injection to simulate partial discharge (PD) is the main method for functional verification of gas insulated switchgear (GIS) ultra high frequency (UHF) PD monitoring device. Due to the different coupling modes of pulse injection in field verification, the equivalence law between simulated PD and actual PD is not clear, and the effectiveness of functional verification of monitoring device cannot be guaranteed. In this paper, a typical PD defect (tip, suspension, insulator bubble) and internal/external pulse injection UHF PD detection platform for 126 kV GIS are established, and the effective pulses of UHF signals are normalized and extracted. Then a signal processing method of weighted intrinsic mode functions (IMF) based on empirical mode decomposition is proposed. The signal equivalence is characterized by calculating the average and maximum values of the Euclidean distance of the signal, and finally compared with the conventional signal deviation method. The research shows that compared with the conventional signal equivalence analysis method, the weighted IMF method can effectively solve the problem of large local difference of UHF signal waveform. The internal sensor pulse injection analog PD and suspended PD have the highest equivalence. The average value Me and the maximum value Ma of Euclidean distance are 3.82% and 10.28%, respectively. Therefore, the function verification of UHF monitoring device can use constant parameter pulse injection instead of suspension defect, and the internal UHF sensor injection can be preferred for analog PD. The research in this paper can provide reference for the pulse injection method for the function verification of UHF PD monitoring device.

We studied a class of nonlinear magnetic diffusion problems with step-function resistivity $ \eta(e) $ in electromagnetically driven high-energy-density physics experiments. The stability of the nonlinear magnetic diffusion equation and its fully implicit scheme, based on the step-function resistivity approximation model $ \eta_\delta(e) $ with smoothing, were studied. A rigorous theoretical analysis was established for the approximate model of one-dimensional continuous equations using Gronwall's theorem. Following this, the stability of the fully implicit scheme was proved using bootstrapping and other methods. The correctness of the theoretical proof was verified through one-dimensional numerical experiments.

Objective To construct SpyCatcher-mi3 nanoparticle vaccine delivery vectors, evaluate their role in enhancing the immunogenicity of the ovalbumin CD8+ T-cell epitope peptide, OVA257-264, and determine its protective effect in a model which mice were immunized and subcutaneously challenged with E.G7-OVA tumor cells. Methods SpyCatcher-mi3 proteins were expressed by E.coli and purified by affinity chromatography and anion exchange chromatography sequentially. OVA257-264-SpyTag peptide was obtained by synthesis. The OVA257-264-mi3 nanoparticles were produced by the SpyTag/SpyCatcher system. The toxicity of OVA257-264-mi3 was evaluated using hemolysis assay, CCK-8 assay and mouse experiment. A total of 42 female SPF-grade C57BL/6 mice (6~8 weeks old, 18~20 g) were randomly divided into OVA257-264-mi3, OVA257-264, and control groups, with 14 mice in each group. Then the mice in each group were immunized on days 0, 14 and 28. In 14 d after the last immunization, the amounts of spot-forming cells (SFCs, indicating IFN-γ secreting cells in splenic lymphocytes) were determined using ELISpot assay to evaluate their immunogenicity. After the immunized mice were subcutaneously implanted with E.G7-OVA tumor cells, the antitumor effect of the vaccine in prophylactic xenograft tumor model was evaluate by observing tumor volumes with a caliper and tumor growth with MRI. Results Both SpyCatcher-mi3 and OVA257-264-mi3 could be self-assembled to form homogeneous and stable nanoparticles, with an average particle size of about 43.8 and 91.3 nm, respectively. The OVA257-264-mi3 was safe for in vitro and in vivo toxicity evaluation. The number of IFN-γ secreting cells per 1×106 splenic lymphocytes reached 253 in the OVA257-264-mi3 group of mice, significantly higher than that in the OVA257-264 group and the Control group (P < 0.05). The tumor volume of mice in the OVA257-264-mi3 group was about 151.1 mm3 on day 22, which was significantly smaller than that of the OVA257-264 group and the Control group (P < 0.05), and the survival rate during the observation period reached 60%, which was significantly higher than that of the OVA257-264 groups (P < 0.05). Conclusion Nanoparticle vaccine OVA257-264-mi3 is successfully constructed, and it shows enhancing effect on the immunogenicity of the antigen epitope peptide, and exerts protective effect on prophylactic xenograft tumor model, providing a theoretical basis for the research of tumor neoantigen vaccines.

Abstract Background Mild cognitive impairment has received widespread attention as a high-risk population for Alzheimer’s disease, and many studies have developed or validated predictive models to assess it. However, the performance of the model development remains unknown. Objective The objective of this review was to provide an overview of prediction models for the risk of Alzheimer’s disease dementia in older adults with mild cognitive impairment. Method PubMed, EMBASE, Web of Science, and MEDLINE were systematically searched up to October 19, 2023. We included cohort studies in which risk prediction models for Alzheimer’s disease dementia in older adults with mild cognitive impairment were developed or validated. The Predictive Model Risk of Bias Assessment Tool (PROBAST) was employed to assess model bias and applicability. Random-effects models combined model AUCs and calculated (approximate) 95% prediction intervals for estimations. Heterogeneity across studies was evaluated using the I 2 statistic, and subgroup analyses were conducted to investigate sources of heterogeneity. Additionally, funnel plot analysis was utilized to identify publication bias. Results The analysis included 16 studies involving 9290 participants. Frequency analysis of predictors showed that 14 appeared at least twice and more, with age, functional activities questionnaire, and Mini-mental State Examination scores of cognitive functioning being the most common predictors. From the studies, only two models were externally validated. Eleven studies ultimately used machine learning, and four used traditional modelling methods. However, we found that in many of the studies, there were problems with insufficient sample sizes, missing important methodological information, lack of model presentation, and all of the models were rated as having a high or unclear risk of bias. The average AUC of the 15 best-developed predictive models was 0.87 (95% CI: 0.83, 0.90). Discussion Most published predictive modelling studies are deficient in rigour, resulting in a high risk of bias. Upcoming research should concentrate on enhancing methodological rigour and conducting external validation of models predicting Alzheimer’s disease dementia. We also emphasize the importance of following the scientific method and transparent reporting to improve the accuracy, generalizability and reproducibility of study results. Registration This systematic review was registered in PROSPERO (Registration ID: CRD42023468780).

In the process of water treatment, the coagulation process is a complex system characterized by significant lag and non-linearity. To address its characteristics and based on the current research status of dosing control, a forward-cascade intelligent dosing system based on floc image processing and fuzzy logic control was developed. Through the acquisition and processing of water sample images, key parameters of floc characteristics were extracted, and the equivalent diameters were calculated to establish a dosing model to determine the coagulant dosage. Subsequently, automatic adjustment and precise dosing of coagulants were achieved through fuzzy PID control and feedforward compensation. System monitoring and performance analysis showed that compared with traditional manual dosing, the intelligent dosing system reduced the standard deviation of the sedimentation effluent turbidity by 27%, with the relative error controlled within 10% of the set value. The dosage of coagulants was reduced by 11.04%. The intelligent dosing system demonstrated significant advantages in coagulant dosage and treatment effects, which showed promising feasibility and potential for dissemination.

NLRP3 inflammasome is a vital component of the innate immune system, crucial in combatting pathogenic infections and responding to danger signals. At the same time, the aberrant activation of NLRP3 inflammasome is intricately linked with diseases such as diabetes, Alzheimer's disease, and lupus erythematosus. Therefore, regulation and intervention of inflammasome activation processes are pivotal for sustaining immune homeostasis and functionality. This review comprehensively summarizes recent progress in elucidating the regulatory mechanisms governing NLRP3 inflammasome activation, including post-translational modifications of NLRP3, interacting molecules, alterations in organelle and cellular localization, as well as metabolic processes and associated metabolites associated with NLRP3 function. Its objective is to offer novel perspectives on understanding inflammasome activation occurrences, inflammatory responses, and therapeutic approaches for inflammation-related disorders.

Purposes As a coal based solid waste rich in silicon and aluminum oxides, utilization of coal gangue is crucial for the sustainable development of coal industry. Methods Integrated grinding modification of calcined coal gangue and aluminate coupling agent to prepare rubber reinforcement was proposed. The influences of grinding time and the amount of modifier on the surface modification were investigated. Ultrafine particles were obtained through air flow classification, and the influences of modification or not and particle size on the reinforcing and filling properties of rubber were analyzed. Findings The results show that the best comprehensive modification effect is achieved when the duration of ball milling is 30 min and the amount of aluminate coupling agent is 2%. The characteristic functional groups of aluminate coupling agent appear on the surface of coal gangue. Compared with the rubber filled with commercial silica, the rubber filled with the air-flow graded modified filler possesses higher hardness and crosslinking density, its vulcanization performance is better, the tensile strength, elongation at break and permanent deformation at break are reduced, and the fixed extension stress is increased. The particle size distribution of the filler has an obvious effect on the properties of rubber, with the decreases of the particle size of the filler, the vulcanization property is improved, and the tensile property is also improved. The reinforcement performance of modified superfine coal gangue as filler is close to that of silica, which has the potential to replace silica.

Abstract Nitrous oxide (N2O) is a climate-active gas with emissions predicted to increase due to agricultural intensification. Microbial reduction of N2O to dinitrogen (N2) is the major consumption process but microbial N2O reduction under acidic conditions is considered negligible, albeit strongly acidic soils harbor nosZ genes encoding N2O reductase. Here, we study a co-culture derived from acidic tropical forest soil that reduces N2O at pH 4.5. The co-culture exhibits bimodal growth with a Serratia sp. fermenting pyruvate followed by hydrogenotrophic N2O reduction by a Desulfosporosinus sp. Integrated omics and physiological characterization revealed interspecies nutritional interactions, with the pyruvate fermenting Serratia sp. supplying amino acids as essential growth factors to the N2O-reducing Desulfosporosinus sp. Thus, we demonstrate growth-linked N2O reduction between pH 4.5 and 6, highlighting microbial N2O reduction potential in acidic soils.

Background Research on the utilization of outpatient and inpatient health services and its influencing factors has been well established, but there are few studies on the utilization of preventive medical services such as health checkup by residents in China. Objective To investigate the utilization of health checkup in Chinese residents aged 45 years and above and analyze its influencing factors. Methods Using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), the population aged≥45 years was selected to calculate the rate of participation in health checkup and the number of health checkup items from 2015 to 2018. Zero-inflation negative binomial regression was used to analyze the influencing factors of the number of health checkup items attended by residents. Results A total of 17 203 samples were included in this study, with an average age of (62.4±10.0), and the participation rate of 47.73% (8 21/17 203). The top three in participation rate in health checkup were Xinjiang Uygur Autonomous Region (96.47%), Shanghai (83.67%) and Beijing (82.05%), while the bottom three were Liaoning Province (35.41%), Qinghai Province (36.55%) and Fujian Province (36.94%). Among the 8 211 people who had participated in health checkup, the average age was (64.1±9.9) years old, and the median number of health checkup items per capita was 9 (5, 12). The top three in the number of health checkup items were Beijing Municipality (14 items), Shanghai Municipality (14 items) city and Xinjiang Uygur Autonomous Region (13 items), and the bottom three were Gansu Province (7 items), Anhui Province (7 items) and Liaoning Province (7.5 items). Non-parametric test showed that the number of health checkup items in urban residents was significantly higher than that in rural areas (10 items vs. 8 items), the eastern region was significantly higher than the central (10 items vs. 8 items), western (10 items vs. 8 items) and northeast (10 items vs. 8 items) region, the western region was significantly higher than the central region (9 items vs. 8 items) (P

Rechargeable zinc-air batteries (ZABs) have gained extensive research attention as a promising sustainable energy technology due to their considerable theoretical specific energy density, low toxicity, abundant availability, and robust safety features. However, the practical implementation of ZABs still faces challenges, primarily attributed to the sluggish kinetics of oxygen-involved reactions, including oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) during the discharge and charge process. Therefore, searching for efficient bifunctional oxygen electrocatalysts is crucial to address these challenges. Dual-atom catalysts (DACs), an extension of single-atom catalysts (SACs), exhibit flexible architectures that allow for the combination of homogeneous and/or heterogeneous active sites, making them highly attractive for improving bifunctional activity. In this review, we first introduce the basic framework of ZABs and the structural characteristics of DACs. Subsequently, we organize the research progress on applying DACs in liquid and solid-state ZABs and elaborate on their unique catalytic mechanism. Finally, we highlight the challenges and future research directions for further innovation of DACs in ZABs. In summary, this review highlights the advantages of DACs compared with SACs used as bifunctional oxygen electrocatalysts and provides a reference for the broad applications of DACs in energy conversion and storage.

Electricity theft detection is very important for the economic benefits of power companies and the effectiveness of safe operation of power systems. At present, the traditional power theft detection method can only identify whether the user has power theft, but cannot perform rapid and accurate inspections for various types of power theft users. Aiming at the characteristics of medium-voltage users with large power consumption and regular power consumption, this paper proposed a method for detecting the type of power theft in medium-voltage distribution lines based on robust regression and convolutional neural network. Firstly, considering the existence of abnormal data due to factors such as communication delay interruption, a robust regression algorithm is used to reduce its impact and improve the accuracy of regression analysis. Secondly, the correction coefficient and error term of each user obtained by regression are taken as the characteristics of user stealing electricity, and input into the convolutional neural network model for training to complete the identification of stealing electricity type. Finally, the method is verified by simulation and measured data. The results show that under different disturbance conditions, the proposed method can accurately identify different types of power stealing behaviors, which can better assist on-site investigation, narrow the investigation scope and improve the verification rate.

Background: Our previous studies have demonstrated that the activated Cholinergic Anti-inflammatory Pathway (CAP) effectively suppresses systemic inflammation and immunity in early sepsis. Some parameters of Heart Rate Variability (HRV) could be used to reflect the regulatory activity of CAP. However, in the early stages of severe sepsis of some patients, the inflammatory storm can still result in multiple organs dysfunction and even death, suggesting they lose CAP's modulation ability. Since CAP is part of the vagus nerve and is directly innervated by the Medullary Visceral Zone (MVZ), we can reasonably concluded that pathological changes induced by MVZ's neuroinflammation should be responsible for CAP's dysfunction in modulating systemic inflammation in early sepsis. Methods: We conducted two independent septic experiments, the sepsis model rats were prepared by cecum ligation and puncture (CLP) method. In the first experiment, A total of 64 adult male Sprague-Dawley rats were included. Under the condition of sepsis and CAP's pharmacological activation or blockade, we investigated the MVZ's pathological changes, the functional state of key neurons including catecholaminergic and cholinergic neurons, key genes' expression such as Oligodendrocyte Transcription Factor 2 (Olig-2) mRNA, glial fibrillary acidic protein (GFAP) mRNA, and matrix metalloprotein (MMP) −9 mRNA, and CAP's activities reflected by HRV. The second experiment involved in 56 rats, through central anti-inflammation by feeding with 10 mg/ml minocycline sucrose solution as the only water source, or right vagus transection excepting for central anti-inflammation as a mean of the CAP's functional cancel, we confirmed that the neuroinflammation in MVZ affected systemic inflammation through CAP in sepsis. Results: In the first experiment, cholinergic and catecholaminergic neurons showed significant apoptosis with reduced expressions of TH, but the expression of CHAT remained relatively unaffected in MVZ in sepsis. HRV parameters representing the tone of the vagus nerve, such as SDNN, RMSSD, HF, SD1, and SD2, did not show significant differences among the three Septic Groups, although they all decreased significantly compared to the Control Group. The expressions of GFAP mRNA and MMP-9 mRNA were up-regulated, while the expression of Olig-2 mRNA was down-regulated in the Septic Groups. Intervention of CAP had a significant effect on cholinergic and catecholaminergic neurons' apoptosis, as well as the expressions of TH/CHAT and these key genes, but had little effect on HRV in sepsis. In the second experiment, the levels of TNF-α, IL-6, in serum and MVZ were significantly increased in sepsis. Central anti-inflammatory treatment reversed these changes. However, right vagotomy abolished the central anti-inflammatory effect. Conclusions: Our study uncovered that MVZ's neuroinflammation may play a crucial role in the uncontrolled systemic inflammation through inflammatory demyelination in MVZ, which disrupts CAP's modulation on the systemic inflammation in early sepsis.

To analyze quantitatively various indexes of wire arc additive manufacturing components of 2319 aluminum alloy, the expressions of curved surface between different process parameters, porosity and tensile strength values were fitted, and the "process-structure-property" corresponding rule was established. In addition, a normalized fuzzy evaluation model was developed for process parameters, organizational defects, and mechanical properties using the generalized fuzzy synthesis operation rule. The purpose of this model was to obtain the optimal process parameters. The results show that the porosity generally increases with the wire feeding speed rising.Then the porosity generally decreases with a decrease in scanning speed. When the scanning speed is 0.035 m/s, the correlation between porosity and tensile strength is the lowest, with a correlation coefficient (coefficient of determination, COD) of only 0.6. The comprehensive evaluation score of the expert is the highest when the wire feeding speed is 5.0 m/min and the scanning speed is 0.025 m/s, indicating that this combination of process parameters is optimal.

In this article, our main aim is to investigate the existence of radial kk-convex solutions for the following Dirichlet system with kk-Hessian operators: Sk(D2u)=λ1ν1(∣x∣)(−u)p1(−v)q1inℬ(R),Sk(D2v)=λ2ν2(∣x∣)(−u)p2(−v)q2inℬ(R),u=v=0on∂ℬ(R).\left\{\begin{array}{ll}{S}_{k}\left({D}^{2}u)={\lambda }_{1}{\nu }_{1}\left(| x| ){\left(-u)}^{{p}_{1}}{\left(-v)}^{{q}_{1}}& {\rm{in}}\hspace{1em}{\mathcal{ {\mathcal B} }}\left(R),\\ {S}_{k}\left({D}^{2}v)={\lambda }_{2}{\nu }_{2}\left(| x| ){\left(-u)}^{{p}_{2}}{\left(-v)}^{{q}_{2}}& {\rm{in}}\hspace{1em}{\mathcal{ {\mathcal B} }}\left(R),\\ u=v=0& {\rm{on}}\hspace{1em}\partial {\mathcal{ {\mathcal B} }}\left(R).\end{array}\right. Here, up1vq1{u}^{{p}_{1}}{v}^{{q}_{1}} is called a Lane-Emden type nonlinearity. The weight functions ν1,ν2∈C([0,R],[0,∞)){\nu }_{1},{\nu }_{2}\in C\left(\left[0,R],\left[0,\infty )) with ν1(r)>0

The seismically active Ka-Ping Block within Xinjiang, China, represents a zone of potential earthquake hazards, and existing surface measurements cannot fully reflect the area’s sub-surface slip rates. To determine these slip rates and characterize the level of hazard that the study area may face in future years, using a cross-correlation of waveforms, we identified 432 repeat sequences along large faults (F1–F5) in the Ka-Ping Block between September 2009 and April 2022 and computed the annual slip rate for every sequence with the empirical relationship of the moment and the seismic magnitude. Spatial distribution images and temporal evolution characteristics of deep deformation in fault zones were constructed. We obtained five asperities in the Ka-Ping Block, the western portion of the PiQiang fault (F4) had a larger yearly slide rate than its eastern portion, and the southwest and eastern areas of the KEP station show an elevated risk of seismic activity within the next two years.

[ Objective ] Carbonatites, as magmatic-origin rocks, are crucial source rocks for uranium, rare earth, and other minerals. They are widely distributed in the Xiaoqinling region of Shaanxi, giving rise to numerous large to super-large carbonatite deposits of uranium, molybdenum, and rare earth, represented by Huayangchuan and Dashigou, attracting attention from scholars in recent years. Previous studies on carbonatite deposits in the area focused on petrology, mineralogy, genesis, and mineralization chronology. However, they were often limited to individual deposits, needing more regional cross-sectional comparative studies. [ Methods ] This study employs field geological surveys, petrographic analysis, and geochemical characterization of typical rocks and ores to reclassify different types and stages of Xiaoqinling carbonatites. It analyzes the geochemical characteristics of various carbonatite types and explores the mineralization processes of uranium and rare earth elements associated with carbonatites. [ Results ] Xiaoqinling carbonatites exhibit a large vein, vein group, and vein network morphology, intruding into the Archean metamorphic basement, Xiong'er Group volcanic sedimentary rocks of the Changchengian System, and Gaoshanhe Group clastic rocks of the Jixianian System along fault structures. Based on field crosscutting relationships and primary mineral assemblage characteristics, Xiaoqinling carbonate rocks can be re-divided into five stages from old to new: aegirine syenite stage (I), aegirine carbonatite stage (II), potassium feldspar carbonatite stage (III), quartz carbonatite stage (IV) and zeolite-bearing carbonatite stage (V). Spatially, the division is roughly along the nearly EW-striking Xiaohe Fault, with northern carbonatite veins dominated by aegirine syenite and aegirine carbonatite, rich in aegirine, biotite and other dark minerals, distributed in the Archean gneiss basement. The southern part is mainly composed of light-colored potassic feldspar carbonatites and quartz carbonatites, almost devoid of dark minerals, with surrounding rocks consisting of Xiong'er Group volcanic sedimentary rocks and Gaoshanhe group clastic rocks. Zeolite-bearing carbonatites are distributed throughout the region. Temporally, the carbonatites formed in the Late Triassic, but distinct temporal differences exist among different sections. Previous data indicate a possible 30 Ma gap in the formation times of various carbonatite types in the Xiaoqinling area. The geochemical characteristics of Xiaoqinling carbonatites reveal an average SiO2 content of 30.43%, significantly higher than the global average for carbonatites. CaO is relatively low, with an average content of 28.71%, exhibiting a clear negative correlation with SiO2 content. Total alkali (Na2O+K2O) content is relatively high, averaging 2.25%, with a maximum value of 10.23%. The total alkali content decreases gradually from early to late stages, strongly correlating with CaO and Al2O3 content. The potassium-sodium ratio (w(K2O)/w(Na2O)) is exceptionally high, with an average of 4.625 and a maximum value of 36.55. Ferromagnesian content (TFe2O3+MgO) varies significantly, with early-stage carbonatites (Stages I, II, III) having higher ferromagnesian content (average 8.29%), while late-stage carbonatites (Stages IV, V) generally have lower ferromagnesian content (average 1.92%). Ferromagnesian content correlates positively with TiO2 content. MnO has an average content of 1.22%, reaching up to 4.49%, notably enriched in late-stage quartz carbonatites. REE content averages 0.26%, with a maximum value of 0.96%, exhibiting a positive correlation with MgO content. The ∑LREE/∑HREE ratio ranges from 0.47 to 27.72, with early-stage carbonatites (Stages I, II, III) showing strong heavy REE depletion. Late-stage quartz carbonatites have an average ∑LREE/∑HREE ratio of 2.15, indicating relatively heavy REE enrichment, especially in Tm, Yb, Lu, and Y. Heavy REE content correlates linearly with MnO content. The overall REE distribution pattern of carbonatites is a steep-left and gentle-right, relatively flat-right-trending model, showing continuous variations in REE distribution patterns throughout different stages. Ore-related element content characteristics of various carbonatite types reveal significant U and Nb enrichment in aegirine syenite, aegirine carbonatite, and potassium feldspar carbonatite. Mo-mineralization is closely associated with potassium feldspar carbonatite and quartz carbonatite, while Pb and Ba-Sr mineralization is evident in all carbonatite stages. [ Conclusions ] (1) Xiaoqinling carbonatites are categorized into aegirine syenites, aegirine carbonatites, potassium feldspar carbonatites, quartz carbonatites, and zeolite-bearing carbonatites in chronological order. (2) Xiaoqinling carbonatites exhibit notably high SiO2 and total alkali content, low MgO content, and exceptionally high potassium-sodium ratio. There is a gradual decrease in CaO, TiO2, Al2O3, ferromagnesian, and total alkali content from early to late stages, while MnO content shows an opposite trend. Carbonatites evolve from early ferrocarbonatite to late calciocarbonatite. (3) Different types of carbonatites show distinct ore-related characteristics, with early stages (aegirine syenite, aegirine carbonatite, and potassium feldspar carbonatite) mainly enriched in U (Nb), and Potassic Feldspar Carbonate additionally enriched in Mo. Late-stage quartz carbonatites are characterized by Mo and HREE enrichment. [ Significance ] The findings of this study provide valuable information for the exploration and research of carbonatite-type uranium, rare earth, and polymetallic deposits in the Xiaoqinling area, holding significant practical importance.

Abstract Background Ubiquitination plays an important role in proliferating and invasive characteristic of glioblastoma (GBM), similar to many other cancers. Tripartite motif 25 (TRIM25) is a member of the TRIM family of proteins, which are involved in tumorigenesis through substrate ubiquitination. Methods Difference in TRIM25 expression levels between nonneoplastic brain tissue samples and primary glioma samples was demonstrated using publicly available glioblastoma database, immunohistochemistry, and western blotting. TRIM25 knockdown GBM cell lines (LN229 and U251) and patient derived GBM stem-like cells (GSCs) GBM#021 were used to investigate the function of TRIM25 in vivo and in vitro. Co-immunoprecipitation (Co-IP) and mass spectrometry analysis were performed to identify NONO as a protein that interacts with TRIM25. The molecular mechanisms underlying the promotion of GBM development by TRIM25 through NONO were investigated by RNA-seq and validated by qRT-PCR and western blotting. Results We observed upregulation of TRIM25 in GBM, correlating with enhanced glioblastoma cell growth and invasion, both in vitro and in vivo. Subsequently, we screened a panel of proteins interacting with TRIM25; mass spectrometry and co-immunoprecipitation revealed that NONO was a potential substrate of TRIM25. TRIM25 knockdown reduced the K63-linked ubiquitination of NONO, thereby suppressing the splicing function of NONO. Dysfunctional NONO resulted in the retention of the second intron in the pre-mRNA of PRMT1, inhibiting the activation of the PRMT1/c-MYC pathway. Conclusions Our study demonstrates that TRIM25 promotes glioblastoma cell growth and invasion by regulating the PRMT1/c-MYC pathway through mediation of the splicing factor NONO. Targeting the E3 ligase activity of TRIM25 or the complex interactions between TRIM25 and NONO may prove beneficial in the treatment of GBM.

AIM:To investigate the changes of retinal microcirculation after phacoemulsification and the influencing factors of visual acuity.METHODS: Retrospective analysis. A total of 264 cataract patients(264 eyes)who underwent phacoemulsification in our hospital from January 2022 to December 2022 were selected as the study objects. Patients were divided into < 0.3 group(66 eyes)and ≥0.3 group(198 eyes)according to the recovery of best corrected visual acuity(BCVA)at 3 mo after surgery. The changes of retinal microcirculation indexes were compared before and after treatment. Logistic regression and LASSO regression models were used to screen the influencing factors of postoperative BCVA. A nomogram prediction model of postoperative BCVA was constructed and verified. A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship between end-diastolic velocity(EDV), peak systolic velocity(PSV)and the risk of BCVA recovery.RESULTS: At 3 mo postoperatively, EDV and PSV were significantly improved compared with those before treatment, and resistance index(RI)levels were significantly lower than those before treatment(all P0.05).CONCLUSION: After phacoemulsification, retinal microcirculation in cataract patients improved significantly. EDV, PSV, aqueous humor cell grade, fundus lesion grade, advanced age and Emery grade are all factors influencing poor BCVA recovery after cataract surgery.

The three-dimensional electrode-electro-Fenton method is a new advanced oxidation method that introduces three-dimensional electrode electrocatalytic technology on the basis of electro-Fenton，which has been widely used in water treatment. The activated brilliant orange X-GN wastewater was used as the treatment object，and the loaded three-dimensional electrode was prepared by excessive impregnation calcination method. The effects of pH，voltage，Fe2+ dosage and electrolyte concentration on the treatment effect were studied by experiments，and the experimental conditions were optimized by response surface method. The results showed that under the condition of pH 4.7，the supply voltage 20.39 V，the dosage of Na2SO4 2.13 g/L，and the dosage of Fe2+ 2.5 mmol/L，the removal rates of COD and chromaticity could reach 85.41% and 92.18%. The loaded three-dimensional electrode-electro-Fenton method has ideal treatment effect on the chromaticity and COD of reactive brilliant orange X-GN wastewater.

Photocatalytic technology shows significant advantages in environmental remediation and catalysis due to use clean solar energy directly and highly mineralization of pollutants. Metal oxides photocatalysts have the disadvantages of a large band gap and high hole-electron recombination. In recent years，MXene have potential applications in the modification of metal oxide with advantages of good electron transfer ability，environmental stability，rich layer structure and large specific surface area. In this paper，the preparation methods of MXene were firstly outlined，including hydrofluoric acid etching，fluoride etching，alkali etching，hydrochloric acid hydrothermal etching，Lewis acid etching，electrochemical etching，chemical vapor deposition and high temperature decomposition method. Secondly，the surface functional groups，dispersibility and chemical stability were introduced. Then，photocatalytic mechanism of MXene/metal oxide photocatalysts was reviewed，including photocatalytic mechanism of metal oxide，photocatalytic activity enhanced mechanism of MXene/metal oxide. Moreover，applications of MXene/metal oxide photocatalysts were introduced，including the photocatalytic degradation of pharmaceutical and personal care products（PPCPs） and dyes，and the photo-stability. Finally，the existing problems of MXene/metal oxide photocatalysts were prospected，which could provide the theoretical supporting for design of efficient photocatalysts and water treatment applications.

Ultra high frequency (UHF) partial discharge (PD) detection is a common method for transformer oil-paper insulation defect location. However, the accuracy of PD positioning in practical application is easily affected by noise and sensor layout. In order to ensure the effectiveness of PD positioning detection of transformer oil-paper insulation defect, an UHF PD positioning detection platform for oil-paper insulation defects is established. Based on the conventional K-means method, a modified clustering demarcation PD anti-interference positioning method is proposed, which effectively reduces the positioning error. Aiming at the problem of sample clustering demarcation aliasing, when the optimal correction coefficient L is 1.1, the UHF PD positioning error can be reduced to less than 0.1 m, which verifies the effectiveness of the proposed method. Finally, the variation law of positioning error of different sensor layout is analyzed, and the optimal layout scheme of UHF sensor for transformer oil-paper insulation defect detection is proposed, which can provide reference for the layout and positioning of transformer on-line monitoring sensor.

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was

Spirulina is widely known as the “Super Nutritious Food of the Future” due to its exceptional nutritional properties. In this article, we investigated the effects of fermentation using a combination of Lactobacillus acidophilus KDB-03 and Kluyveromyces marxianus GDMCC 2.119 on Spirulina. Fermentation significantly increased the total flavonoid and phenol levels in Spirulina, and enhanced the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging capacity and ferric-reducing antioxidant power. Untargeted ultra-performance liquid chromatography-electrospray tandem mass spectrometry-based metabolomics and gas chromatography-ion mobility spectrometry analysis revealed alterations in the metabolites and flavor components of fermented Spirulina (FS). Furthermore, a mice experiment demonstrated that FS could effectively alleviate metabolism-associated fatty liver disease (MAFLD) by regulating liver metabolism, intestinal flora, and facilitating communication between the liver and gut. These findings suggest that fermentation could be a innovative approach to enhance the diversity of Spirulina products, and potentially be used as a strategy for the prevention and treatment of MAFLD.

Abstract Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation‐induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation‐induced senescence in non‐neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence‐associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor‐promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

Weakly supervised semantic segmentation (WSSS) aims to segment objects without a heavy burden of dense annotations. Pseudo-masks serve as supervisory information for training segmentation models, which is crucial to the performance of segmentation models. However, the generated pseudo-masks contain significant noisy labels, which leads to poor performance of the segmentation models trained on these pseudo-masks. Few studies address this issue, as these noisy labels remain inevitable even after the pseudo-masks are improved. In this paper, we propose an uncertainty-weight transform module to mitigate the impact of noisy labels on model performance. It is noteworthy that our approach is not aimed at eliminating noisy labels but rather enhancing the robustness of the model to noisy labels. The proposed method adopts a frequency-based approach to estimate pixel uncertainty. Moreover, the uncertainty of pixels is transformed into loss weights through a set of well-designed functions. After dynamically assigning weights, the model allocates attention to each pixel in a significantly differentiated manner. Meanwhile, the impact of noisy labels on model performance is weakened. Experiments validate the effectiveness of the proposed method, achieving state-of-the-art results of 69.3% on PASCAL VOC 2012 and 39.3% on MS COCO 2014, respectively.

Abstract Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

With the increasing penetration of distributed power sources, the stochastic and fluctuating nature of distributed power sources poses a great challenge to the reactive power optimization of the distribution network system. In this study, a dynamic reactive power optimization model with two-stage robust optimization is established, proposing whether the energy storage is charged or discharged. The number of groups of group-switching capacitors is taken as the variables in the first stage. The power of the energy storage charging and discharging and the amount of static reactive power compensator compensation are placed in the second stage. The control strategy in the first stage ensures that the control strategy in the second stage can maintain the safe and stable operation of the distribution network under the worst scenarios. The grid-storage joint optimization technology based on distributed architecture establishes an optimization planning model for the distribution network energy storage system with the goal of optimal technical and economic performance of the transmission and distribution network and considering the constraints of safe and stable operation of the transmission and distribution network, respectively. The PG&E-69 node system arithmetic example is used to verify the effectiveness and feasibility of the proposed model and algorithm. The results of the arithmetic example show that the strategy obtained based on the robust optimization model can achieve voltage magnitude stability within the safety range of 1.0-1.05 p.u. in the simulation scenario that has the best economy. At the same time, the mismatches of each distribution system under cooperative planning are all 0, which indicates that the proposed optimization strategy can fully cooperate with the resources of transmission and distribution networks, promote the safe consumption of clean energy, effectively improve the economy of transmission and distribution networks, and achieve the goal of “mutual benefit and win-win”.

To realize the safe operation of electric power site, this paper proposes an intelligent recognition technology to automatically identify violations. This study successfully constructs a face detection model for power operation sites by combining deep convolutional neural networks and target detection algorithms. A three-way connected feature pyramid structure containing a neuron self-processing module is adopted, and an accuracy test is completed using a Tri-FPN-based target detection network, significantly improving recognition accuracy. In this paper, we also utilized the on-site images collected by video surveillance equipment, combined with CNN algorithm and HOG feature extraction technology to effectively identify the violations and provide early warning of the breaches of the personnel at the power operation site. MAP curves evaluated the detection performance, and the results showed that the head recognition rate was up to 0.9913, and the accuracy rate of all violations exceeded 0.9350.The high accuracy of CNN-based feature fusion extraction algorithm in the recognition of violations of personnel at the site of electric power operation provides effective technical support to ensure personnel safety.

This paper firstly focuses on the automatic detection of mental health in colleges and universities and the sequential quadratic programming algorithm, proposes a psychological abnormality detection model for college students based on the sequential quadratic programming algorithm, and in the feature vectorization process, uses constraint functions and coefficient matrices to process various types of features into vector sequences of length k weeks to help quantify the trajectory of students’ school activities, and trains and establishes a student psychological abnormality detection model. Then, on the technical basis of the psychological abnormality detection model, the mental health education system is constructed, the online and offline integration teaching development is realized through the teaching system, and the performance of the education system is verified. The results show that the average score of the traditional psychological teaching model 1-10 week test is 76.52, compared to the average score of 78.51 in the mental health education system teaching 1-10 test, with an error value of 1.89. This study uses the mental health teaching system to retrieve information on students with current mental health problems at any time, and there this is to realize dynamic online and offline coeducation.

This paper first analyzes the characteristics and components of students’ core literacy in higher education institutions and constructs a flipped classroom teaching model under the deep learning perspective. Secondly, a Stacking integration-based model for student core literacy features classification is constructed by integrating Lasso regression, random forest, and XGBoost algorithms as base learners. Finally, a case study was conducted to verify the effectiveness of the flipped classroom model in cultivating students’ core literacy. The results showed that the p-values of moral quality, professionalism, humanistic literacy, and practical innovation of students under the flipped classroom teaching model were 0.022, 0.038, 0.012, and 0002, respectively, all of which were less than 0.05, with significant differences. The flipped classroom teaching model can effectively develop students’ core literacy, as shown by this.

BackgroundThe silicon photomultiplier (SiPM) is sensitive to environmental noise, its performance is greatly affected by ambient noise.PurposeThis study aims to design a negative-feedback selective amplifier circuit for SiPM coupled plastic scintillator detector to reduce the noise and improve the overall performance of SiPM.MethodsIt is compared with the traditional OPA657 transimpedance feedback amplifier circuit. The circuit consisted of an RC filter input and an integrated operational amplifier AD8014 with advantages of a high gain and low input noise. The CR high-pass filter circuit was used as the comparator signal input to further filter out signal noise and prevent signal reflection from interfering with the amplifier. The experimental circuit is simulated using Micro-cap12 to obtain the relevant circuit parameters. Finally, the dark noise level and signal consistency of a 137Cs source at room temperature was record, and performance of this amplifier circuit for SiPM coupled plastic scintillator detector was compared with that of the traditional OPA657 transimpedance feedback amplifier circuit. [Results and Conclusions] Comparison results show that the proposed circuit effectively filters out ambient noise and exhibits a fast rise time. The output pulse rise time is found to be less than 12 ns, and the dark noise level is observed to be less than 30 mV, which are better than those of the transimpedance amplifier circuit.

The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand–receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.

Battery demand as a power source has skyrocketed due to the electric car market’s explosive growth. Because of its high energy density, lack of memory effect, low self-discharge rate, environmental friendliness, and extended cycle life, lithium-ion batteries, or LIBs, are widely employed in electric cars, aircraft, and other sectors. However, the use of traditional carbon materials in LIBs has led to relatively low specific capacity, limited charging and discharging rates, and low first-time charging and discharging efficiencies Carbon nanotubes (CNTs), with their high electrical conductivity, excellent mechanical properties, and thermal conductivity, can bring higher capacity, better cycling stability, excellent thermal conductivity, as well as lightweight and flexibilization to LIBs. Therefore, this paper first introduces the basic properties of CNTs and their preparation methods. Then, their roles in the positive and negative electrodes of LIBs are discussed respectively. Finally, an outlook on the future development of LIBs is made. This has a reference value for the future development of LIBs.

Under the impact of the COVID-19 pandemic, the global economy has undergone profound changes, presenting unprecedented challenges to the job market for college graduates. This paper focuses on students in the field of economics and management, employing methods such as surveys, forums, and in-depth interviews to analyze the employment dilemmas and their causes in the post-pandemic era for college students. The study finds that students face a series of issues in aspects like employment information access, work skills, job-seeking conditions, professional qualities, social cognition, and career development. To address these challenges, the paper proposes six countermeasures and work plans, including improving employment services, strengthening school-enterprise cooperation, using data for guidance, conducting quality development, enhancing cognitive internship management, and statistical analysis of historical data. The aim is to enhance students’ employability and professional qualities, better adapting them to the job market in the post-pandemic era.

This study investigates the integrated application of cloud computing and big data in the field of education and its impact on curriculum teaching. Through a comprehensive review of the fundamental principles, current applications, and relevant literature, the study reveals the advantages and challenges of cloud computing and big data in aspects such as curriculum design, learning analytic, and personalized teaching. It also explores their influence on aspects like the sharing of teaching resources, the construction of online learning environments, and the evaluation of student learning outcomes. Furthermore, through case analysis and empirical studies, this paper provides a more in-depth validation of the practical effects of cloud computing and big data in improving teaching effectiveness, promoting educational innovation, and cultivating students’ information literacy. In summary, the integration of cloud computing and big data provides new perspectives and solutions for building smart education, while also laying a solid foundation for nurturing talents capable of meeting the demands of future society.

Domestic sewage is prone to deposit in the sewer system due to its complex composition and lengthy collection and transportation route. The migration and transformation of pollutants between deposits and sewage during the deposition process play a vital role in the sound and stable operation of the sewer system, the enhancement of the centralized collection rate of domestic sewage, and the safeguarding of urban water environments. Built on research findings worldwide, this paper summarizes the generation pattern and composition characteristics of the deposition and attenuation of pollutants in domestic sewage within the sewer system. The leading factors influencing sewage pollutant deposition are explored, and the harm engendered by the migration and transformation of pollutants between deposits and sewage is analyzed. Finally, we express hopes for addressing the issue of sewage pollutant deposition and attenuation, aiming to enhance the quality and efficiency of sewage treatment and foster the green and healthy development of sewer systems.

One new meroterpene derivative, millmerranones G ( 1 ), and three known analogues ( 2 - 4 ) were identified from the mangrove-derived fungus Aspergillus sp. GXIMD 03004, which was isolated from the leaves of mangrove Acanthus ilicifolius L. collected from Beibu Gulf in China. The structure of 1 was characterised by a comprehensive interpretation of the NMR spectroscopic and HRESIMS data. The absolute configuration for 1 was established using experimental and calculated ECD data. The anti- Vibrio activities of all compounds were evaluated, the result showed that compounds 1 and 2 has weak activity against Vibrio harveyi .

A pair of atropisomers secofumitremorgins C ( 1a ) and D ( 1b ), together with fifteen known alkaloids ( 2-16 ), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

A new polyketide, mauritone A ( 1 ) with six known polyketides curvulone B ( 2 ), curvularin ( 3 ), 12-oxocurvularin ( 4 ), (10 E ,15 S )-10,11-dehydrocurvularin ( 5 ), (11 R ,15 S )-11-hydroxycurvularin ( 6 ), and (11 S ,15 S )-11-hydroxycurvularin ( 7 ) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/ Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica . Their structures were elucidated by extensive spectral analysis. All compounds ( 1 - 7 ) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4 , 5 , and 7 on nitric oxide (NO) production were found to be significant, with IC 50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 μM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 μM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC 50 values of 18.6 ± 0.53 and 12.7 ± 0.45 μM, respectively.

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Protection against oxidative stress is a vital defense mechanism for Mycobacterium tuberculosis within the host. However, few transcription factors that control bacterial antioxidant defense are known. Here, we present evidence that SdrR, encoded by the MSMEG&#95;5712 (Ms5712) gene, functions as an oxidative stress response regulator in Mycobacterium smegmatis. SdrR recognizes an 11-bp motif sequence in the operon's upstream regulatory region and negatively regulates the expression of short-chain dehydrogenases/reductases (SDR). Overexpressing sdrR inhibited SDR expression, which rendered the strain oxidative more stress-sensitive. Conversely, sdrR knockout alleviates SDR repression, which increases its oxidative stress tolerance. Thus, SdrR responds to oxidative stress by negatively regulating sdr expression. Therefore, this study elucidated an underlying regulatory mechanism behind mycobacterial oxidative stress adaptation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

The multispecies biofilm is a naturally occurring and dominant lifestyle of bacteria in nature, including in rhizosphere soil, although the current understanding of it is limited. Here, we provide an approach to rapidly establish synergistic multispecies biofilm communities. The first step is to extract cells from rhizosphere soil using the differential centrifugation method. Afterward, these soil cells are inoculated into the culture medium to form pellicle biofilm. After 36 h of incubation, the bacterial composition of the biofilm and the solution underneath are determined using the 16S rRNA gene amplicon sequencing method. Meanwhile, high-throughput bacterial isolation from pellicle biofilm is conducted using the limiting dilution method. Then, the top 5 bacterial taxa are selected with the highest abundance in the 16S rRNA gene amplicon sequencing data (pellicle biofilm samples) for further use in constructing multispecies biofilm communities. All combinations of the 5 bacterial taxa were quickly established using a 24-well plate, selected for the strongest biofilm formation ability by the crystal violet staining assay, and quantified by qPCR. Finally, the most robust synthetic bacterial multispecies biofilm communities were obtained through the methods above. This methodology provides informative guidance for conducting research on rhizosphere multispecies biofilm and identifying representative communities for studying the principles governing interactions among these species.

Background: Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined., Methods: A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS)., Results: A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p  < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS., Conclusion: Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Chang, Ye, Gao, Zhu, Liu, Zhou, Zheng and Yang.)

As a type of elementary organic compounds containing N-N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N 2 -retention and N 2 -removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N 2 -moiety of hydrazone by a radical facilitated N-N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann-Löffler-Freytag reaction by the reaction of N-homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino-N migration and H-atom transfer. Consequently, a series of structurally significant ϵ-N-sulphonamide-α,α-difluoro-γ-amino acid esters are efficiently produced via continuous C-C bond and dual C-N bonds forging., (© 2024 Wiley‐VCH GmbH.)

Objectives: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI., Methods: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats., Results: Compared with the normal group, the rats' random blood glucose contents were significantly increased ( P <0.01), the escape latency prolonged ( P <0.01), and the original platform crossing counts reduced ( P <0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index ( P <0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins ( P <0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content ( P <0.01), shortened escape latency ( P <0.01), increased original platform crossing counts ( P <0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index ( P <0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins ( P <0.05, P <0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins ( P <0.01)., Conclusions: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

In the chemistry community, catalytic asymmetric synthesis of furan-based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing to the importance and difficulty in constructing such frameworks. In this work, we have realized the first catalytic asymmetric synthesis of five-five-membered furan-based compounds bearing both axial and central chirality via organocatalytic asymmetric (2+4) annulation of achiral furan-indoles with 2,3-indolyldimethanols with uncommon regioselectivity. By this strategy, furan-indole compounds bearing both axial and central chirality were synthesized in high yields with excellent regio-, diastereo-, and enantioselectivities. Moreover, theoretical calculations were conducted to provide an in-depth understanding of the reaction pathway, activation mode, and the origin of the selectivity., (© 2023 Wiley-VCH GmbH.)