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Chun-Hai Gao,1 Yan-An Zhang,2,3 Mao-Shui Wang3– 5 1Department of Clinical Laboratory, Linyi People’s Hospital, Linyi, People’s Republic of China; 2Department of Cardiovascular Surgery, Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, People’s Republic of China; 4Department of Laboratory Medicine, Shandong Provincial Chest Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Department of Laboratory Medicine, Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Yan-An Zhang, Department of Cardiovascular Medicine, Shandong Public Health Clinical Center, 46# Lishan Road, Jinan, 250103, People’s Republic of China, Email zhangtbgroup@163.com Mao-Shui Wang, Department of Laboratory Medicine, Shandong Provincial Chest Hospital, 46# Lishan Road, Jinan, 250013, People’s Republic of China, Email wangmaoshui@gmail.comObjective: To evaluate the performance of interferon-γ release assays (IGRAs) in patients with Mycobacterium kansasii infection.Methods: Consecutive patients between May 2012 and June 2021 who had positive for mycobacterial cultures and who underwent IGRAs (T-SPOT.TB or QuantiFERON-TB Gold [QFT-G]) were included in the analysis. The IGRA positivity rates among patients with M. kansasii isolates were then calculated. If M. kansasii was identified in at least two sputum samples or in sterile samples, M. kansasii disease was then diagnosed. Otherwise, colonisation was considered.Results: During the study period, 54 patients with M. kansasii infection underwent T-SPOT.TB (n=48) or QFT-G (n=6) assays. The mean age was 44.1± 13.4 years, 85.2% (46/54) were male. Eight patients were diagnosed with M. kansasii disease and another 46 patients were considered to have colonisation. Twenty-four patients (T-SPOT.TB, n=23; QFT-G, n=1) were positive for IGRAs, for an overall rate of 44.4% (24/54; T-SPOT.TB, 47.9% [23/48]; QFT-G, 16.7% [1/6]) for IGRAs, 25.0% (2/8) for M. kansasii disease, and 47.8% (22/46) for colonisation.Conclusion: Positive IGRA rates were relatively low in patients with M. kansasii infection. More efforts are required to improve the performance of IGRAs in diagnosing M. kansasii infection.Keywords: interferon-gamma release assay, tuberculosis, M. kansasii, diagnosis, infection

Xiao-Yang Chu,1–3,* Wei Huang,2,* Yu-Li Wang,1 Ling-Wei Meng,2 Li-Qing Chen,2 Ming-Ji Jin,2 Lu Chen,1 Chun-Hong Gao,1 Cheng Ge,3 Zhong-Gao Gao,2 Chun-Sheng Gao11State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China; 2State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China; 3Department of Stomatology, The 5th Medical Center of Chinese PLA General Hospital, Beijing 100071, P.R. China *These authors contributed equally to this workBackground: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status.Methods: In this study, a solvent-injection method was used to prepare paclitaxel–cholesterol complex-loaded lecithin–chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized.Results: The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration.Conclusion: In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy. Keywords: lecithin, chitosan, paclitaxel, nanoparticles, pH responsive, palliative chemotherapy, intratumoral injection

Chu-Han Gao,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities), socioeconomic, and cultural factors. Levofloxacin (LVX) is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.Methods: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.Results: In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be associated with sample size and administration route. Children younger than 5 years cleared LVX nearly twice as fast as adults. Patients in intensive care receiving LVX therapy showed significant pharmacokinetic differences compared with healthy subjects. Creatinine clearance explained most of the population variance in the plasma clearance of LVX. Switching from intravenous to oral delivery of LVX had economic benefits. Addition of tamsulosin to the LVX regimen was beneficial for patients with bacterial prostatitis because tamsulosin could increase the maximal concentration of LVX in prostatic tissue. Coadministration of multivalent cation-containing drugs and LVX should be avoided. For patients receiving warfarin and LVX concomitantly, caution is needed regarding potential changes in the international normalized ratio; however, it is unnecessary to seek alternatives to LVX for the sake of avoiding drug interaction with warfarin. It is unnecessary to proactively reduce the dose of cyclosporin or tacrolimus when comedicated with LVX. Transporters such as organic anion-transporting polypeptide 1A2, P-glycoprotein, human organic cation transporter 1, and multidrug and toxin extrusion protein 1 are involved in the pharmacokinetics of LVX.Conclusion: Personalized LVX therapeutics are necessary for the sake of better safety, clinical success, and avoidance of resistance. New findings regarding individual dosing of LVX in special patient populations and active transport mechanisms in vivo are opening up new horizons in clinical practice.Keywords: drug interactions, fluoroquinolone resistance, individual dosing, patient complexity, personalized medicine, pharmacokinetics, pharmacodynamics, therapeutics

With the increasing demand for data sharing in the Internet of vehicles, reliable identity authentication protocols and scientifically rational incentive mechanisms have become the primary conditions for ensuring the stable operation of the Internet of vehicles network. Blockchain, as a decentralized distributed ledger, provides a technologically advanced data sharing platform for the Internet of vehicles, making the combination of blockchain technology and the Internet of vehicles a feasible new approach to data sharing. This paper summarizes the requirements of the Internet of vehicles, analyzes the blockchain-based Internet of vehicles architecture, and divides it into the cloud layer, mechanism layer and edge layer. It categorizes and compares the existing solutions for authentication protocols and incentive mechanisms in blockchain-based Internet of vehicles systems by summarizing relevant literature. It summarizes the workflow and implementation solutions of existing trustworthy authentication mechanisms by analyzing the distributed and centralized authentication architectures. It categorizes existing incentive mechanisms into value-based, trust-based and individual decision-based incentive mechanisms. Finally, this paper summarizes the existing problems and solutions of trustworthy authentication and incentive mechanisms from the perspectives of privacy protection and typical attacks. It provides an outlook on future research directions for blockchain-based Internet of vehicles, focusing on data sharing, multi-vehicle cooperation, and the integration of 6G technology.

Societal Impact Statement Globalization and rapid shifts in culture and economy threaten indigenous and local knowledge (ILK) systems, and large intergenerational gaps in this knowledge already exist. Buddleja asiatica is a deciduous shrub or small tree with traditional medicinal applications but is currently largely overlooked as a medicinal resource. This study investigates the traditional uses of B. asiatica in indigenous communities in the Pan‐Himalayan region through ethnobotanical field surveys, with a view to preserving cultural heritage and strengthening economic resilience in these communities, as well as developing B. asiatica as a medicinal resource. Prioritizing the well‐being of mountain communities, this study aims to bridge community development with nature. Summary Buddleja asiatica Lour. (Scrophulariaceae) is widely distributed across the Pan‐Himalayan region. It has traditional medicinal applications and cultural value, as well as ecological significance. We conducted an ethnobotanical study combining field surveys from Nepal and Xizang, China with a literature review using Web of Science (WoS) to review the ethnobotanical, phytochemical, and pharmacological aspects of this species. Our study highlights the cultural significance of B. asiatica within indigenous communities and, in particular, the use of the leaves to make a starter culture for the preparation of wine. However, an evident intergenerational gap in knowledge transfer exists. The phytochemical investigation revealed the presence of various chemical classes (carbohydrates, terpenoids, flavonoids, saponins, esters, steroids, glycosides, and fatty acids), of which 15 phytoconstituents were first reported from various parts of B. asiatica. The potential medicinal properties of these chemicals include anti‐inflammatory, antioxidant, cytotoxic, antihepatotoxic, antimicrobial, and cholinesterase activities. We combine these lines of evidence to show the prospects for the livelihoods of local people across this region and propose future research directions.

Atrial fibrillation (AF) is among the most prevalent types of arrhythmia, leading to severe complications such as heart failure and stroke, thus increasing rates of mortality and disability. Silent AF, which lacks clinical symptoms and has irregular onset, tends to have a low diagnosis rate and often experiences delays in receiving standardized treatments, resulting in negative clinical outcomes. Recent clinical studies highlight the significant benefits of wearable devices in the screening and management of silent AF. In this article, we review the clinical outcomes, cost-effectiveness, challenges and future application prospects of wearable devices in the detection and management of silent AF based on relevant domestic and international literature of recent years to provide more evidence-based support for its further applications.

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.

BackgroundAs individuals age, they commonly experience reduced physical activity and cognitive decline. While evidence, there is limited trajectory research on their concurrent progression and interrelation in individuals over 55 years old.MethodsThe data was collected from 5,765 individuals aged over 55 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2020. Physical activity was measured by IPAQ, cognitive function by episodic memory, and mental intactness score. Separate sets of group-based trajectory models were fitted to identify physical activity trajectories and cognitive function trajectories. Multivariate logistic regression was used to estimate the association between baseline characteristics and each set of trajectories. Group-based dual trajectory modeling (GBDTM) was applied to quantify these associations.ResultsGBDTM identified three distinct trajectory groups for physical activity and cognitive outcomes. The physical activity trajectories were classified as “Persistently low physical activity” (74.2%), “Decreasing physical activity” (13.7%), and “Rising physical activity” (12.1%). Similarly, cognitive function trajectories were categorized as “Persistently low cognitive function” (22.2%), “Persistently moderate cognitive function” (37.9%), and “Persistently high cognitive function” (39.9%). Notably, 15.6% of participants followed the trajectories of “Persistently low physical activity” and “Persistently low cognitive function.” The presence of a severe decline in physical activity was associated with an increased likelihood of poor cognitive function and vice versa. Age, sex, education, residential status, BMI, and visual impairment were identified as significant predictors for physical activity and cognitive decline.ConclusionThis study found that the GBDTM can determine the consistent trajectories of physical activity and cognitive function trajectories that persistently decline in individuals over 55 years. Analyses of predictive factors can be instrumental in promoting physical activity and delaying cognitive decline.

BackgroundPsoriasis is a chronic inflammatory skin disease characterized primarily by erythema and scales, having a wide-ranging impact globally. Previous studies have suggested that dietary consumption habits may influence psoriasis. The objective of this study was to determine the causal relationship between dietary consumption habits and psoriasis using the Mendelian Randomization (MR) approach.MethodsSNP data for 29 dietary consumption habits and psoriasis were obtained from the GWAS catalog database and the FinnGen database, respectively. The Mendelian Randomization analysis was performed using R software, with the 29 dietary consumption habits as the exposure factors and psoriasis as the outcome. Three MR analysis methods—Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), and MR-Egger regression—were employed to study the causal relationship between dietary consumption habits and psoriasis.ResultsThe IVW analysis indicated an OR (95%CI) of 0.065 (0.008–0.555), p = 0.012, demonstrating a negative correlation between the consumption of dried fruit and psoriasis.ConclusionAmong the 29 dietary consumption habits analyzed, the intake of dried fruits is a protective factor against psoriasis. Therefore, it is clinically advisable to appropriately increase the intake of dried fruits among patients with psoriasis, serving as a nutritional therapy method in conjunction with pharmacological treatment.

BackgroundDiurnal temperature range (DTR) is associated with the increased risk of morbidity and mortality. However, the relationship between DTR and emergency ambulance calls (EACs), which more accurately and immediately reflect the health impacts of temperature changes, remains underexplored in China.MethodsWe collected daily data on EACs and meteorological factors from 2009 to 2017 in Guangzhou, China. DTR, representing the temperature range within a day, was calculated by subtracting the minimum temperature from the maximum temperature for each day. Generalized additive models were used to estimate the association between DTR and EACs for all-cause, cardiovascular diseases, and respiratory diseases. Additionally, subgroup and sensitivity analyses were conducted in our study.ResultsWe found significant associations between daily DTR and EACs. The excess risks (ERs) were 0.47% (95% CI: 0.14, 0.81%) for all-cause EACs, 0.94% (95% CI: 0.46, 1.43%) for cardiovascular-related EACs, and 1.31% (95% CI: 0.76, 1.86%) for respiratory -related EACs at lag01, respectively. Subgroup analyses indicated that these associations were notably stronger among the older, males, and during the warm season. Specifically, there was an increase of 1.16% (95% CI: 0.59, 1.74%) in cardiovascular-related EACs among the older adult, compared to 0.45% (95% CI: −0.21, 1.12%) among those younger than 65 years. Among males, the increase was 1.39% (95% CI: 0.79, 1.99%), compared to 0.13% (95% CI: −0.53, 0.79%) among females. During the warm season, the increase was 1.53% (95% CI: 0.74, 2.34%), compared to 0.75% (95% CI: 0.14, 1.37%) during the cold season.ConclusionDTR might increase the risk of daily all-cause, cardiovascular-related, and respiratory-related EACs in Guangzhou, China. The associations were particularly strong among older adults, males, and during the warm season. Implementing public health policies is essential to mitigate the adverse health effects of DTR.

Abstract Background Hypoxia inducible factor‐1α (HIF‐1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF‐1α on ischemic stroke (IS). Methods IS model was established using middle cerebral artery occlusion (MCAO)‐modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)‐treated mice hippocampal cells HT22, followed by the silencing of HIF‐1α and the overexpression of C‐X‐C motif chemokine receptor 4 (CXCR4) and nuclear factor‐kappa B (NF‐κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5‐triphenyltetrazolium chloride and hematoxylin‐eosin staining. The levels of tumor necrosis factor‐α, Interleukin (IL)‐6, IL‐1β, malondialdehyde, and 8‐hydroxy‐2′‐deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R‐modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2′‐7′dichlorofluorescin diacetate (DCFH‐DA) probe. The levels of HIF‐1α, CXCR4, and NF‐κB p65 were quantified via Western blot and immunofluorescence, respectively. Results HIF‐1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF‐κB p65 in MCAO‐modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF‐κB. Also, in OGD/R‐treated HT22 cells, HIF‐1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF‐κB p65, while promoting viability. However, CXCR4/NF‐κB p65 overexpression did the opposite. Conclusion HIF‐1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF‐κB pathway.

BackgroundFibroblast growth factor receptor 1 (FGFR1) is known to play a crucial role in the pathogenesis of asthma, although the precise mechanism remains unclear. This study aims to investigate how DNA methylation-mediated silencing of FGFR1 contributes to the enhancement of NF-κB signaling, thereby influencing the progression of asthma.MethodsRT-qPCR was utilized to assess FGFR1 mRNA levels in the serum of asthma patients and BEAS-2B, HBEpiC, and PCS-301-011 cells. CCK8 assays were conducted to evaluate the impact of FGFR1 overexpression on the proliferation of BEAS-2B, PCS-301-011, and HBEpiC cells. Dual-luciferase and DNA methylation inhibition assays were performed to elucidate the underlying mechanism of FGFR1 gene in asthma. The MassARRAY technique was employed to measure the methylation levels of the FGFR1 DNA.ResultsElevated FGFR1 mRNA levels were observed in the serum of asthma patients compared to healthy controls. Overexpression of FGFR1 in BEAS-2B cells significantly enhanced cell proliferation and stimulated NF-ĸB transcriptional activity in HERK-293T cells. Furthermore, treatment with 5-Aza-CdR, a DNA demethylating agent, markedly increased the expression of FGFR1 mRNA in BEAS-2B, PCS-301-011, and HBEpiC cells. Luciferase activity analysis confirmed heightened NF-ĸB transcriptional activity in FGFR1-overexpressing BEAS-2B cells and BEAS-2B cells treated with 5-Aza-CdR. Additionally, a decrease in methylation levels in the FGFR1 DNA promoter was detected in the serum of asthma patients using the MassARRAY technique.ConclusionOur findings reveal a potential mechanism involving FGFR1 in the progression of asthma. DNA methylation of FGFR1 inactivates the NF-ĸB signaling pathway, suggesting a promising avenue for developing effective therapeutic strategies for asthma.

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.

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.

As the demand for international travel escalates, the individual health passport has emerged as an essential instrument for verifying the health status of travelers and fulfilling entry criteria. To tackle the challenges associated with the global sharing of individual health passports, including information fragmentation, privacy concerns, and the risk of counterfeiting, a blockchain-based scheme for the secure storage, sharing, and verification of individual health passports was developed. This scheme employed a hybrid on-chain and off-chain storage methodology and incorporated searchable encryption with blockchain technology. This integration aimed to streamline blockchain storage, alleviating the storage load while guaranteeing the dependable archiving and secure dissemination of user-sensitive data. The scheme also refined the weak consensus mechanism, with an improved algorithm that achieved consensus in merely two stages. This innovation significantly diminished the communication complexity among nodes and amplified the throughput capacity of the blockchain system. To cater to multi-user environments, the scheme introduced and enhanced aggregate signature technology. This enhancement minimized the computational load associated with signature verification and facilitated the swift identification of potential malicious forgers. An exhaustive security analysis was conducted to substantiate the scheme's security and dependability. Subsequent simulation outcomes indicate that, in comparison to existing solutions, the proposed scheme realizes substantial optimizations of up to 49.89% in computational overhead and 25.81% in communication overhead within multi-user contexts. Moreover, the proposed consensus mechanism demonstrates significant efficiency benefits across varying node counts.

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

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.

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.

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.

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

[ 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.

In order to improve the mechanical and tribological properties of polytetrafluoroethylene (PTFE), carbon nanotubes (CNTs) nano-capsules loaded with the isobutene sulfide (T321) in the internal cavity (CNTs@T321) were proposed as the reinforcing phase of PTFE. T321 can be released from the nano-capsules during friction to make PTFE have better lubrication properties. First, the effects of filling amount on the mechanical and tribological properties of PTFE composites were studied. The existing forms of nano-capsules in PTFE composites were analyzed, and the self-lubrication mechanism during friction was revealed. The results show that the tensile strength of PTFE can be improved when the content of nano-capsules is lower, and the strength of PTFE can be decreased when the mass fraction of nano-capsules exceeds 3%. Under different speeds and loads, the filling of nano-capsules can reduce the friction coefficient and wear rate of PTFE. The anti-friction effect are improved with the increase of load, while the wear rate will be increased. During the friction process, nano-capsules can release T321 with the wear of PTFE, and T321 forms a self-lubricating layer on the wear interface, thus producing anti-friction and anti-wear effects.

Highlights A simple two-step multi-element co-doping strategy is proposed to fabricate core-shell structured LiCoO2 based on the different diffusivities of dopant ions. The high diffusivity Al3+/Mg2+ ions occupy the core of single-crystal grain while the low diffusivity Ti4+ ions enrich the shell layer. In-situ XRD demonstrates the mitigated structural distortion under a high cut-off voltage of 4.6 V, resulting in a significantly improved cycling stability.

Abstract Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function. Graphical Abstract

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.

DC line protection is the key to the development of flexible DC grids, and fault identification within 3 ms is required. Existing scholars have proposed a digital twinning based flexible DC line protection method with high speed and sensitivity advantages. However, its reliability is easily affected by transformer measurements, which may lead to protection misoperation. The requirements of DC control protection equipment can be hardly meted by existing bad data detection methods with insufficient accuracy and rapidity. Therefore, in order to improve the reliability of this protection method, a self-correcting method of bad data based on the moving average method is proposed in this paper. The predicted value of the measured data is obtained by using the moving average method according to the time sequence characteristics of the steady change of the measured data, and the bad data is detected and corrected by comparing the predicted error and the actual error, without iterative calculation and pre-trained model. The results of a simulation test using the four-terminal flexible DC grid show that the proposed method has higher accuracy and rapidity with good error correction performance than any existing method does, and it can be adapted to the protection method and improve the anti-interference capability as well as the reliability of protection in an effective manner.

ObjectiveThis study aimed to assess the risk of dietary exposure and study the residues of β-receptor agonists in livestock meat and liver marketed in Tianjin City.MethodsA total of 583 samples of pig， beef， mutton， and liver were randomly collected from supermarkets， online stores， and farmers’ markets in Tianjin City from 2016 to 2021. The β-receptor agonists clenbuterol， ractopamine， salbutamol， and terbutaline were tested by the relevant standard operating procedures of Manual China National Food Contamination and Harmful Factors Risk Monitoring， combined with residents’ food consumption data， using the index of food safety （IFS） to assess the health risk.ResultsThe overall detection rate of the 583 samples was 13.89% （81/583）. The main β-receptor agonist detected was clenbuterol， which accounted for 98.77% （80/81） of all the detected samples. Only 1 sample was detected with salbutamol， and the other 2 β-receptor agonists were not detected. The top 3 food categories in terms of detection rate were beef liver， 33.96% （36/106）； mutton， 15.79% （18/114）； and beef， 13.22% （16/121）， while the detection rate of pork and pig liver was 1.19% （1/84） and 2.00% （1/50）， respectively； the difference between the detection rates of the different categories was statistically significant （χ2=56.11， P < 0.05）. The detection rate of β-receptor agonists in samples collected from farmers’ markets was significantly higher than that collected from supermarkets and online shops （χ2= 10.91， P < 0.05）. The exposure risk assessment showed that the average exposure of pork， beef， and mutton ranged from 0.000 1 to 0.000 4 μg/kg·BW. The IFS ranged from 0.022 0 to 0.095 0， and the IFS values were less than 1.ConclusionA certain detection degree of β-receptor agonists was observed in livestock meat and liver marketed in Tianjin City， but the average exposure risk of β-receptor agonists was low from the dietary exposure of pig， beef， and mutton.

Abstract Background Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. Methods A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. Results The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH. Conclusions Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.

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.

Lithium (Li) metal is a potential anode material for high energy density batteries. However, issues such as lithium dendrite growth, interface instability, poor cycling stability and large volume expansion limit the application of lithium metal anode. Aiming at the problem of dendritic growth and volume expansion, a semi-confined hierarchical porous carbon (HPC) material with a large specific surface area was prepared by template method. The high specific area of HPC electrode can reduce the local current density of Li deposition, and the rich pore structure can restrict the Li deposition in it, thus inhibiting the dendritic growth and alleviating the volume expansion. Li‖HPC battery can cycle for more than 250 cycles at a current density of 1.0 mA/cm2 and a deposition capacity of 1.0 mAh/cm2, maintaining a Coulombic efficiency of 97.6%. Li@HPC‖lithium iron phosphate a deposition capacity of (LiFePO4) full cell has a specific capacity of 93.6 mAh/g after 100 cycles at 0.5 C, which is higher than that of Li@Cu‖LiFePO4 full cell (60.8 mAh/g) with an increase of by 32.8 mAh/g.

Abstract Fisetin, a natural flavonoid, possesses numerous biological activities that have been extensively studied in various diseases. When it comes to cancer, fisetin exhibits a range of biological effects, such as suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration. Moreover, fisetin has the ability to enhance the effectiveness of chemotherapy. The anticancer properties of fisetin can be attributed to a diverse array of molecules and signaling pathways, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1. Consequently, fisetin holds promise as a therapeutic agent for anticancer treatment. In this review, we place emphasis on the biological functions and various molecular targets of fisetin in anticancer therapy.