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Lingling Wang,1 Huiguo Liu,1 Ling Zhou,1 Pengdou Zheng,1 Hai Li,2,3 Huojun Zhang,4,* Wei Liu2,3,* 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huojun Zhang, Email hjzhang@whu.edu.cn; Wei Liu, Email 404793938@tjh.tjmu.edu.cnAbstract: Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.Keywords: intermittent hypoxia, hypoxia-inducible factor 1 alpha, nonalcoholic fatty liver disease, oxidative stress, dyslipidemia, leptin resistance

Regeneration of adsorption saturated activated carbon by traditional electrochemical technology has the advantages of high regeneration efficiency and no mass loss of activated carbon, but it has defects such as low mineralization efficiency, generation of toxic by-products, and high energy consumption. Electrochemical advanced oxidation(E-AOP) regeneration technology can effectively overcome the problems of traditional electrochemical regeneration. In this paper, the regeneration efficiency and mechanism of activated carbon by traditional electrochemical are briefly described, and the effects of operating parameters (current, electrolyte type and concentration, regeneration location,anode material, etc.) on the desorption-adsorption balance and the mineralization efficiency of pollutants are analyzed. The mechanism and application of three types of E-AOP regeneration technologies(electro-Fenton regeneration, electro-peroxone regeneration, and electro-persulfate regeneration) in the process of activated carbon regeneration are summarized. The electric-Fenton regeneration technology has better regeneration effect, and the problem of metal ion pollution in the system can be effectively overcome by new regeneration. The electro-peroxone regeneration technology does not require the addition of any chemicals and catalysts, which is conducive to the control of reaction conditions and automation of the regeneration process. The electro-persulfate regeneration technology is convenient in operation with low energy consumption and wide applicability. Finally, the problems and development prospects of E-AOP regeneration technology are proposed. This review provides theoretical basis for the development of new efficient and environmentally friendly activated carbon regeneration technologies.

C/C-HfC composites with a density of 2.14 g/cm3 was successfully prepared using an inorganic hafnium solution as a precursor via chemical vapor infiltration (CVI) and precursor infiltration pyrolysis (PIP) methods, and its microstructure and composition were analyzed. The results show that the HfC ceramics are uniformly dispersed in the pores of the matrix and closely bonded to the matrix. The material's ablation resistance is significantly enhanced by introducing HfC ceramics. Under the same heat flux conditions, when the ablation time is 120 s, the linear and mass ablation rates of the C/C-HfC composite are 6.20×10-2 mm·s-1 and 2.03×10-2 g·s-1, respectively, which are reduced by 48.33% and 40.12%, respectively, compared to those of the C/C composite. During the ablation process, HfC would react with oxygen in the heat flux to generate molten HfO2, which uniformly covers the surface of the matrix to form a protective layer, isolates the heat flux, prevents oxidation of the matrix, and prevents heat transfer. The evaporation of molten HfO2 also takes away some of the surface's heat. With the increase of ablation time, the loss of HfO2 will gradually increase, the protective layer on the surface of the matrix will be gradually destroyed, and the ablation damage of the heat flux on the matrix would become more severe.

Objective: Studies have revealed a higher prevalence of diabetes insipidus in patients following resection of pituitary adenoma surgery. By comprehensively analysing the clinical history of patients undergoing endoscopic transnasal sphenoidal resection for pituitary adenomas, the factors influencing development of postoperative diabetes insipidus were investigated and a predictive model was developed to assess its risk. Methods: A retrospective analysis was conducted on the medical records of 281 patients with pituitary adenomas who underwent neuroendoscopic transsphenoidal resection at our institution between October 2020 and October 2022. The Mann-Whitney U test, chi-square test, and logistic regression analysis were used to identify the independent factors that potentially contribute to the development of postoperative diabetes insipidus. Additionally, a nomogram was constructed to evaluate the predicted risk of postoperative diabetes insipidus in patients with pituitary adenomas. Results: Diabetes insipidus occurred in 100 (35.59 %) of the 281 enrolled patients. The results of the multifactorial logistic regression analysis revealed that diabetes, hypertension, cardiopathy, preoperative serum cortisol level, cerebrospinal fluid leakage, and tumour texture independently influenced the occurrence of postoperative diabetes insipidus (P

BackgroundThe brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression.MethodsA total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs. The presence of CMBs in patients was determined by SWI, and history, renal function related to CMBs were analyzed.ResultsOut of 164 participants in the safety analysis, 36 (21.96%) exhibited CMBs and 128 (78.04%) did not exhibit CMBs, and the median age of the patients was 66 years (range: 49–86 years). Multivariate logistic regression identified hypertension (OR = 13.95%, 95% CI: 4.52, 50.07%), blood urea nitrogen (BUN) (OR = 1.57, 95% CI: 1.06–2.40), cystatin C (CyC) (OR = 4.90, 95% CI: 1.20–22.16), and urinary β-2 microglobulin, (OR = 2.11, 95% CI: 1.45–3.49) as significant risk factors for CMBs. The marginal R-square (RM2) was 0.25. Among all determinants, hypertension (47.81%) had the highest weight, followed by UN (11.42%). Quasi-curves plotted using the bootstrap method (999 times) showed good agreement between the predictive model and actual observations.ConclusionHypertension, BUN, urinary β-2 microglobulin, CyC were risk factors for CMBs morbidity, and controlling the above indicators within a reasonable range will help to reduce the incidence of CMBs.

Artificial materials for the potential treatment of bone defects are very trendy in such research fields. To investigate a hydrogel scaffold with better mechanical strength and osteoinductivity is always a challenge since brittle and soft properties are always the problems in traditional hydrogels. In our study, a novel gelatin/chitosan hydrogel crosslinked by a double network filled with lignin and calcium silicate is fabricated. Enhancements of mechanical strength, low swelling ratio, and improvement in osteoinductivity were achieved in this composite double network hydrogels. The results revealed that lignin was a key factor in raising the compressive strength and stability of the hydrogel because more hydrogen bonds were formed between lignin and the crosslinking network. Even after swelling equilibrium, the compressive strength remained almost unchanged. In addition, the hydrogel groups with a higher ratio of lignin also had lower cytotoxicity and improved osteoinductivity of pre-osteoblasts while the increasing concentration of calcium silicate progressively weakened these performances. Therefore, the gelatin/chitosan double network hydrogel reinforced by lignin would be a potential bone tissue-engineered artificial material.

TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.

This study explored the regulatory role of bta-miR-149–3p in the inflammatory response induced by microcystin-leucine arginine (MC-LR) exposure in bovine Sertoli cells. The research endeavored to enhance the comprehension of the epigenetic mechanisms underlying MC-LR-induced cytotoxicity in Sertoli cells and establish a foundation for mitigating these effects in vitro. In this study, we elucidated the regulatory mechanism of bta-miR-149–3p in the MC-LR-induced inflammatory response by verifying the target gene of bta-miR-149–3p through luciferase assays and treating the cells with a bta-miR-149–3p inhibitor for 24 h. The results demonstrate that nuclear factor κB (NF-κB) acts as a downstream target gene of bta-miR-149–3p, which inhibits the MC-LR-induced inflammatory response in bovine Sertoli cells. This inhibition occurs by regulating the downregulation of tight junction constitutive proteins of the blood-testis barrier (BTB) through the suppression of the TLR-4/NF-κB signaling pathway (p < 0.05) and the up-regulation of the adhesion junction protein β-catenin (p < 0.05). Notably, MC-LR exposure resulted in the up-regulation (p < 0.05) of inflammatory cytokines (IL-6, IL-1β, and NLRP3) and the down-regulation (p < 0.05) of BTB tight junction constitutive proteins (ZO-1, Occludin) in Sertoli cells. Furthermore, the BTB constitutive protein ZO-1 exhibited significant down-regulation in Sertoli cells pretreated with the bta-miR-149–3p inhibitor compared to controls (p < 0.05), while Occludin showed no significant difference from CTNNB1 (p > 0.05). In summary, our findings suggest that bta-miR-149–3p suppresses the MC-LR-induced inflammatory response and alterations in the expression of BTB proteins in bovine Sertoli cells by inhibiting the TLR-4/NF-κB signaling pathway.

【Objective】 Climate change is anticipated to lead to increased frequency of extreme weather events such as droughts and floods, which have significant implications for water availability in catchment areas. In this paper, we analyze extreme runoff events in the Tianshan region in northwestern China and their correlation with climate change. 【Method】 The analysis was based on data measured over the past 60 years from the Kaidu River Basin in the region. The variation in its runoff events was analyzed using the Sen slope, MK test, Pettitt test and probability distribution function, coupled with the SWAT model and the GCM model. 【Result】 ① Annual runoff and seasonal runoff, except in spring in which the runoff has seen a significant increase, in the basin have been increasing, albeit not at significant levels. Runoff changes are correlated to precipitation more than to temperature. ②Over the past 60 years, frequency, intensity and duration of extreme runoff events have been increasing, and there is a delay in the occurrence of the first flood in each year. ③ The Log-Pearson3 function is optimal for modelling extreme runoff events. The returning times of floods was 50 years, the maximum duration of flooding events and average peak flow rate of floods were 7.09 times, 79.04 days and 180.04 m3/s, respectively. ④ Under projected climate change scenarios, the frequency of flooding events will increase, average annual maximum flow rate in the floods will amplify, maximum duration and average duration of floods, as well as average intensity of floods will all increase. The first flooding in each year will arrive early, and extreme runoff intensity is the highest under the SSP245 scenario and the lowest under the SSP370 scenario. 【Conclusion】 Climate change significantly influences extreme runoff events in the Tianshan region, resulting in increased frequency and severity of both extreme runoff events and single large flood. These findings have important implications for improving management strategies to mitigate the adversary impact of extreme weathers induced by climate changes.

Abstract Background Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. Materials and methods With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. Results Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1β), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-β1 (TGF-β1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. Conclusion IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice. Graphical Abstract

Baojun Guo,1,2 Hui Gan,1 Mingshan Xue,1,3 Zhifeng Huang,1 Zhiwei Lin,1 Shiyun Li,1 Peiyan Zheng,1 Baoqing Sun1 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 3Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Baoqing Sun; Peiyan Zheng, Email sunbaoqing@vip.163.com; gdmcslxx@126.comBackground: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade.Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes.Results: From 1990 to 2019, China’s age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India’s rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China’s age-standardized incidence rate is projected to rise.Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.Keywords: COPD, global burden of disease, risk factors, DALYs

Abstract Rockbursts are a complex phenomenon characterized by a violent ejection of rock fragments from the free face of deep underground mines. Due to the sudden, disruptive, and complex nature of these events, accurate predictions of rockbursts are difficult. Therefore, geotechnical intervention is imperative to prevent the occurrence of a rockburst. The scenarios of microwave destressing is introduced here as an application method to potentially prevent their occurrence. To understand the influences of microwave destressing, such as microwave exposure duration, spatial layout, and geometric parameters of the microwave preconditioned zone (MPZ), on the occurrence of a rockburst, numerical simulation was conducted based on an impact-induced rockburst model. The feasibility of microwave destressing technology was validated numerically. This paper also provides guidance for the utilization of microwave destressing in practice. Discontinuous MPZ is suitable for a known blasting source with a fixed position, and continuous MPZ can be applied for a working condition with multiple blasting sources with variable positions. A closer distance of MPZ from the free face results in a better microwave destressing effect. However, the closer distance of MPZ from the free face also introduces more negative influences on the static stability of surrounding rock.

Abstract State estimation is critical for railway power supply systems (RPSSs). Pseudo‐measurement is commonly used in state estimation. However, the fluctuations of renewable generations and railway traction loads in RPSS may introduce data noise, which will jeopardize the accuracy of the generated pseudo‐measurements and thus impact the state estimation. Additionally, when learning the historical measurement data sequences, the traditional pseudo‐measurement model is likely to have overfitting, which will further impact the accuracy of pseudo‐measurements, thereby affecting the accuracy of state estimation. To address these issues, this paper proposes a high‐accuracy pseudo‐measurement‐based state estimation approach for RPSSs. Firstly, a denoising autoencoder‐based method is used to mitigate the impact of data noise on the accuracy of pseudo measurements, and a gated recurrent unit‐based method is used to adaptively learn the historical measurement data sequence, thereby improving the accuracy of pseudo measurements. Next, the pseudo‐measurement weights are obtained by generating pseudo‐measurement variances using the Gaussian mixture model. Finally, the pseudo measurements and real‐time measurements are integrated by weighted least squares to realize the state estimation of RPSS. The effectiveness and accuracy of the proposed method are verified by simulation on a modified IEEE 33‐node system which includes a railway traction substation and renewable generations.

Xue-Er Zhang,1 Pai Zheng,1 Sheng-Zhen Ye,1,2 Xiao Ma,3 E Liu,1 Yao-Bin Pang,1 Qing-Ying He,1 Yu-Xiao Zhang,1 Wen-Quan Li,1 Jin-Hao Zeng,4 Jing Guo2 1Chengdu University of Traditional Chinese Medicine, Chengdu, 6610075, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 6610072, People’s Republic of China; 3State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Jing Guo, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, 610072, Chengdu, Sichuan Province, 6610072, People’s Republic of China, Tel + 86 18980880167, Email Guojing66@cdutcm.edu.cn Jin-Hao Zeng, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, 610072, Chengdu, Sichuan Province, 6610072, People’s Republic of China, Tel + 86 15999931573, Email zengjinhao@cdutcm.edu.cnAbstract: As the body’s largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.Keywords: skin microbiota, inflammatory skin diseases, atopic dermatitis, seborrheic dermatitis, rosacea, acne, psoriasis, diaper dermatitis, Malassezia folliculitis

The Yellow River is the main source of water for urban and rural area and agricultural irrigation in northern China. Herein, the distribution and risk assessment of perfluoroalkyl acids (PFAAs) were investigated from the Yellow River in Shandong Province, China. The total concentration of PFAAs (∑PFAAs) in surface water and sediments were 37.5–2128 ng/L (mean: 167 ng/L) and not detected−6.95 ng/g dry weight (dw) (mean: 1.02 ng/g dw), respectively. Short-chain PFAAs-perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulfonic acid (PFBS) were the most prevalent PFAAs in surface water. Source analysis showed that firefighting foam (proportion: 31.3 %) and textile treatments and food packaging (proportion: 30.3 %) were the main sources of PFAAs in water. Based on the concentration of PFAAs in water, ecological and potential human health risks were assessed. Perfluorooctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) and perfluoroundecanoic acid (PFUnDA) posed nonnegligible ecological risk for some aquatic organisms. Levels of PFAAs (e.g., PFOA, PFNA, and PFDA etc.) in some water samples were higher than the advisory guidelines of PFAAs concentrations in water worldwide, indicating a potential human health risk. Therefore, PFOA, PFNA, PFDA, and PFUnDA are the key focus of pollutants in the water of the Yellow River in Shandong Province, and the standards and limits of these PFAAs in environments including surface water and sediment should be promoted.

BackgroundUrolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive.MethodMendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis.ResultsOur study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848–0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-β) (OR = 1.150, 95% CI = 1.009–1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1β) (OR = 0.863, 95% CI = 0.779–0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (β = 0.145, 95% CI = 0.013–0.276) and cutaneous T cell-attracting chemokine (CTACK) (β = 0.145, 95% CI = 0.013–0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (β = 0.142, 95% CI = 0.057–0.226), interleukin-7 (IL-7) (β = 0.108, 95% CI = 0.024–0.192), interleukin-8 (IL-8) (β = 0.127, 95% CI = 0.044–0.210), growth regulated oncogene alpha (GRO-α) (β = 0.086, 95% CI = 0.004–0.169), monokine induced by interferon-gamma (MIG) (β = 0.099, 95% CI = 0.008–0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (β = 0.126, 95% CI = 0.044–0.208) levels.ConclusionThese discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-β and MIP-1β influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.

With the growing dependence on lithium-ion batteries, there is an urgent need to understand the potential developmental toxicity of LiPF6, a key component of these batteries. Although lithium’s toxicity is well-established, the biological toxicity of LiPF6 has been minimally explored. This study leverages the zebrafish model to investigate the developmental impact of LiPF6 exposure. We observed morphological abnormalities, reduced spontaneous movement, and decreased hatching and swim bladder inflation rates in zebrafish embryos, effects that intensified with higher LiPF6 concentrations. Whole-mount in situ hybridization demonstrated that the specific expression of the swim bladder outer mesothelium marker anxa5b was suppressed in the swim bladder region under LiPF6 exposure. Transcriptomic analysis disclosed an upregulation of apoptosis-related gene sets. Acridine orange staining further supported significant induction of apoptosis. These findings underscore the environmental and health risks of LiPF6 exposure and highlight the necessity for improved waste management strategies for lithium-ion batteries.

The grid assembly within ion thruster exhibit characteristics of high voltage differentials and small spacing, making them susceptible to beam sparkle phenomenon, which has a certain impact on the overall stability and reliability of the ion electric propulsion system. Therefore, it is imperative to fully consider the beam sparkle factor during the design process. This article begins by conducting the topology selection and key parameters design of the high-voltage power supply of the ion electric propulsion system, and then establishes the electrical equivalent circuit model of the three-grid structure. Using this model, the flow paths of the beam sparkle current are analyzed when different grounding methods and grounding positions are employed. The advantages and disadvantages of each grounding strategy are discussed accordingly. Furthermore, this article delves into an analysis of the mechanism by which common-mode noise is generated due to beam sparkle currents. It also presents corresponding solution ideas to mitigate this noise. On the basis of theoretical analysis and discussion, we perform simulations and verified the key conclusions.

This paper summarized the Traditional Chinese Medicine (TCM) nursing of a patient with postoperative pain after surgery for breast cancer. The patient had received a comprehensive nursing assessment after hospital admission. Based on the TCM syndrome differentiation, appropriate technique of TCM nursing including TCM ointment massage, cupping therapy, TCM medication and emotional care were carried out to relieve the negative emotion and postoperative pain of the patient. (本文总结1例乳腺癌患者术后疼痛的中医状态调护经验。患者入院后完善护理评估, 基于中医辨证, 采取中药膏摩、拔罐疗法、口服中药、情志护理等中医护理适宜技术干预, 有效改善患者负性情绪, 减轻疼痛, 有助于提高肿瘤患者生存质量。)

In this study, a new deep-penetration variable-polarity tungsten inert gas (DP-VPTIG) welding process, which is performed by a triple-frequency-modulated pulse, was employed in the welding fabrication of 8 mm AA7075 aluminum plates. The electric signal, arc shape, and weld pool morphology of the welding process were obtained by means of high-speed photography and an electric signal acquisition system under varying parameters of the intermediate frequency (IF) pulse current. The principle of the arc characteristics and the dynamic mechanism of the weld melting during the process are explained. In addition, the macroforming, microstructure, and microhardness of the welded joints were investigated. The results indicate that, with an intermediate frequency pulse of 750 Hz, the arc displayed a higher energy density and a more effective arc contraction, which improved weld appearance and penetration. Moreover, the impact and stirring action of the arc refined the microstructure grains of the weld center. Therefore, this new welding method is feasible for welding medium-thickness aluminum alloy plates without a groove.

The widespread use of Unmanned Underwater Vehicles (UUVs) in seafloor observatory networks highlights the need for docking stations to facilitate rapid recharging and effective data transfer. Floating docks are promising due to their flexibility, ease of deployment, and recoverability. To enhance understanding and optimize UUV docking with floating docks, we employ dynamic fluid body interaction (DFBI) to construct a seabed moored suspended dock (SMSD) model that features a guiding funnel, a suspended body, and a catenary of a mooring chain. This model simulates SMSD equilibrium stabilization in various ocean currents. Then, a UUV docking model with contact coupling is developed from the SMSD model to simulate the dynamic contact response during docking. The accuracy of the docking model was validated using previous experimental data. Through investigation of the UUV docking response results, sensitivity studies relating to volume, moment of inertia, mass, and catenary stiffness were conducted, thereby guiding SMSD optimization. Finally, sea tests demonstrated that the SMSD maintained stability before docking. During docking, the SMSD’s rotation facilitated smooth UUV entry. After the UUV docked, the SMSD was restored to its original azimuth, confirming its adaptability, stability, and reliability.

BackgroundTokamak plasma disruption generates a runaway current carrying enormous amounts of energy that, if not suppressed, can cause severe damage to equipment.PurposeThis study aims to investigate the effects of injecting a deuterium-argon/neon gas mixture on a runaway current during plasma disruption.MethodsBased on the high plasma current discharge conditions of the HL-2M tokamak device in China, numerical simulations were conducted using a fluid model in the DREAM code. Variations of plasma parameters, such as plasma current (Ip), ohmic current (Iohm), runaway current and the ohmic electric field, with the injected deuterium-argon content and ratio during the disruption process were consistently simulated.ResultsResults show that injecting a deuterium-argon/neon gas mixture suppresses the eventual formation of a platform runaway current, and an optimal content and ratio of the deuterium-argon/neon gas mixture are existed for effective runaway current suppression. Within the range of the pre-disruption plasma current (Ip) discussed in this study, the amounts of neon/argon and deuterium in the gas mixture should be 0.50%~0.70% and 1020~1021 m-3, On fusion-reactor-scale tokamak devices with Ip as high as 10 MA, the amount of the injected gas mixture must reach 1022 m-3, which cannot be achieved under the current massive gas injection (MGI) technique.ConclusionsThe pre-disruption plasma current (Ip) is the key factor that influences a runaway current. The larger Ip is, the larger is the runaway current that is formed and more amount of the gas mixture must be injected. On fusion-reactor-scale tokamak devices with Ip as high as 10 MA, the amount of the injected gas mixture must reach 1022 m-3, which cannot be achieved under the current massive gas injection technique. Injecting a deuterium-argon/neon gas mixture through a shattered pellet would be a more viable approach.

Abstract Triple‐positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan‐human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin‐dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II–III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%–84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0–I was 75% (95% CI, 46.8%–91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%–98.5%). Mean Ki‐67 level was significantly reduced from 45.0% (95% CI, 19.5%–70.5%) at baseline to 17.2% (95% CI, 0.7%–33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment‐related deaths occurred. This four‐drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

Objective To build a model of postoperative pathological fracture of the mandibular angular cystic lesions through 3D finite element analysis (FEA), to compare and analyze the biomechanical changes of the mandible after treatment with 8 types of titanium plates, and explore the reliability of titanium plate fixation in preventing pathological fracture of large mandibular cysts. Methods A 30-year-old healthy male was volunteered and the scans of cone beam computed tomography of his mandible were collected to establish a unilateral cystic lesion model of the mandibular angle region to mimic the pathological fracture caused by occlusal force loading. On the basis of the maximum critical cystic lesion size, the biomechanical characteristics and changes in the mandible with 8 different types of titanium plate fixation under the same mechanical conditions were compared. Results The risk of pathological fracture existed when the cystic lesion size in the mandibular angle exceeds 24 mm×30 mm×30 mm. The stress in the lesion area was the lowest when the upper edge was fixed with 1 mm thick titanium plate and bilateral 3 screws, and the lower edge was fixed with 2 mm thick titanium plate and bilateral 4 screws. At the same time the maximum yield strength of the mandible was not exceeded and no pathological fracture of the mandible occurred. Conclusion The incidence of pathological fracture can be reduced by using titanium plate fixation on the upper and lower margins of the mandibular angle after extraoral surgical curettage for large cystic lesions.

Pingping Zheng,1,&ast; Yating Lu,2,&ast; You Tang,1,&ast; Fudong Xu,3 Lin Wang,2 Rui Qian,4 Cancan Hui,5 Qian Xu,2 Jianle He,1 Datong Deng2 1The General Practice Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 2The Endocrinology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 3The Pathology Department, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Shoudu Medical University, Beijing, People’s Republic of China; 4The Neurology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 5The Geriatric endocrinology Department, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Datong Deng, Tel +86 13855134251, Fax +86 055163633742, Email 13855134251@163.comBackground: To investigate the change in hypothalamic kisspeptin-1 (Kiss1) expression during the development of polycystic ovary syndrome (PCOS) and hypoglycemic drug intervention.Methods: Letrozole lavage was used to construct a polycystic ovary rat model. After successful modeling, we treated PCOS rats with metformin, pioglitazone, and acarbose, and we then observed changes in weight, estrus, glucose tolerance, insulin resistance, sex hormones, and hypothalamic kiss1 expression.Results: PCOS rats exhibited increased body weight, abnormal estrous cycle, impaired glucose tolerance, insulin resistance, increased testosterone level, increased luteinizing hormone level, and increased Kiss1 expression in the hypothalamus. However, intervention with metformin, pioglitazone, and acarbose improved the reproductive and metabolic disorders as well as reduced hypothalamic Kiss1 expression.Conclusion: The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. Metformin, pioglitazone, and acarbose may reduce the expression of hypothalamic Kiss1 by improving insulin resistance, thereby improving reproductive and metabolic disorders in PCOS rats.Keywords: polycystic ovary syndrome, PCOS, kisspeptin, metformin, pioglitazone, acarbose

In order to solve the problem of tooth surface eccentric load caused by shaft deflection angle of large internal meshing gears of the shield machine, the tooth surface equation of comprehensively modified tooth surface is given, and the method of neural network combined with orthogonal test is proposed to screen and predict the tooth surface modification parameters. In this method, the tooth profile modification and tooth direction modification are no longer regarded as independent variables, and the eccentric load on the tooth surface can be transformed into the load evenly distributed on the tooth surface. Through the contact analysis of the modified gear by the finite element method, it is found that this method can effectively reduce the excessive local stress on the tooth surface caused by the shaft deflection angle and reduce the transmission error. The optimal tooth surface modification parameter value can be found at one time, which avoids the high cost of meshing experiment for the internal meshing gear of large shield machines.

As an emerging type of large commercial building, commercial complexes play an increasingly important role in contemporary urban development and construction trends. In order to better study the organization of public space relations in commercial complex buildings, this paper selects eight commercial complexes as sample cases to analyze their spatial design in terms of both content public space and external public space based on big data technology. Regarding the design of the commercial complexes’ internal public space movement, the highest accessibility degree reached 95.3%, while the average was 82.5%. Regarding visibility, the highest level was 96.0%, and the average was 83.3%. For large complexes, better spatial relationships can be designed to improve the circulation degree and thus enhance customers’ consumption experience. Regarding the convenience of traffic connection to the external space of commercial complexes, an average of 41.4% of customers consider it very convenient, 23.1% consider it relatively convenient, 27.9% consider it somewhat inconvenient, and 18.0% consider it very inconvenient. Commercial complexes can effectively attract more repeat customers if they can improve the convenient design of transportation connections. The study of public relations of commercial complexes based on big data helps to discover the defects of their public space design and plays a significant role in optimizing spatial design and relationship organization and strengthening their integrated functions.

The crosslinking network structure is a crucial factor influencing the properties of natural rubber. Therefore, investigating the impact of different vulcanization bond types on the strain-induced crystallization behavior and properties of natural rubber can provide a theoretical foundation for producing high-performance natural rubber. In this study, diverse curing systems were employed to produce vulcanized natural rubbers with varying crosslink types. The crosslinking network structures of the vulcanized rubbers were analyzed using the tube model theory. Additionally, the effects of vulcanization bonds on strain-induced crystallization behavior and tensile properties were examined through in-situ X-ray diffraction and a tensile testing machine. The results revealed that the vulcanizate with monosulfidic bonds, formed under the effective vulcanization (EV) system, primarily comprised chemical crosslinking networks, resulting in a high tensile modulus, low elongation at break, and low tensile strength. Conversely, the vulcanizate under the conventional vulcanization (CV) system exhibited a distinct entanglement network impact compared to the chemical crosslinking network, resulting in a smaller tensile modulus but the highest elongation at break and the largest tensile strength. These differences stemmed from the distinct roles of vulcanization bonds within the crosslinking network. Specifically, the relatively short monosulfidic bond quickly reached the critical degree of orientation for crystallization during stretching, leading to higher crystallinity under the same strain. However, its shorter length caused earlier fracture during stretching, resulting in network heterogeneity, reduced elongation at break, and lower tensile strength. On the other hand, the longer polysulfidic bond underwent fracture recombination during stretching, with slower orientation and delayed crystallization. Nonetheless, this recombination improved network uniformity and integrity due to stress dissipation from the initial fracture, enhancing crystallinity, elongation at break, and tensile strength. This study elucidated the influence of vulcanization crosslinking on the tensile properties of vulcanizates.

Hybrid wheel–track systems have found extensive applications due to the advantages a combination of wheels and tracks. However, the coupling influence between the wheeled and tracked mechanisms poses a challenge to stable and efficient controller design and implementation. This paper focuses on the lateral dynamic control of a vehicle in scenarios where both tracks and wheels are in contact with the ground. A dynamic model of a vehicle is first established based on the tire brush model and linearized general track model. Based on the dynamic model, a novel adaptive model predictive control (AMPC) method is designed considering the coupling and nonlinearity of the wheels and tracks to simultaneously regulate both mechanisms. Compared with traditional model predictive control approaches, the AMPC controller takes the side-slip angle and slip ratio as constraints to prevent the vehicle from reaching unstable states. Simulations are conducted to validate the effectiveness of the controller, and the results indicate that the controller has the capacity to optimize the objective’s yaw-rate response while maintaining lateral vehicle stability and preventing slip by imposing constraints.

To address the question of which posture trailing-arm vehicles (TAVs) should be adopted while driving, this study introduces an innovative active posture controller (APC) to improve both path-following and handling stability performance. Leveraging a nonlinear tire model that considers corner load variation and wheel camber, alongside the kinematics and double-track model of TAVs, the impact of vehicle body posture on handling performance has been investigated. To fully utilize the four-wheel independent drive and posture adjustable characteristics of the TAV mechanisms, an integrated nonlinear model predictive control (NMPC) combining APC and tire forces distribution is devised. Through simulations conducted using Simulink-Multibody (2023a), the effectiveness of the proposed controller is demonstrated, particularly when compared to the scheme that does not account for the unique posture adjustment mechanisms of TAVs.

The development of underwater acoustic networks is a significant expansion of Internet-of-Things technology to underwater environments. These networks are essential for a variety of marine applications. For many practical uses, it is more efficient to collect marine data from a remote location over multiple hops, rather than direct point-to-point communications. In this article, we will focus on the underwater acoustic string network (UA-SN) designed for this type of application. We propose a Robust and Adaptive Pipeline Medium Access Control (RAP-MAC) protocol to enhance the network’s transmission efficiency, adaptability, and robustness. The protocol includes a scheduling-based concurrent algorithm, online real-time configuration adjustment function, a rate mode adaptive algorithm, and a fault recovery algorithm. We conducted simulations to compare the new protocol with another representative protocol, validating the RAP-MAC protocol’s adaptability and fault recovery ability. Additionally, we carried out two large-scale sea trials. The results of these experiments indicate that the RAP-MAC protocol ensures effectiveness and reliability in large-scale multihop UA-SNs. In the South China Sea, we were able to achieve a communication distance of 87 km with a throughput of 601.6 bps, exceeding the recognized upper bound of underwater acoustic communication experiment performance by 40 km·kbps.

Atractylodes lancea is a perennial herb whose rhizome (AR) is a valuable traditional Chinese medicine with immense market demand. The cultivation of Atractylodes lancea faces outbreaks of root rot and deterioration in herb quality due to complex causes. Here, we investigated the effects of Trichoderma spp., well-known biocontrol agents and plant-growth-promoters, on ARs. We isolated Trichoderma strains from healthy ARs collected in different habitats and selected three T. harzianum strains (Th2, Th3 and Th4) with the strongest antagonizing effects on root rot pathogens (Fusarium spp.). We inoculated geo-authentic A. lancea plantlets with Th2, Th3 and Th4 and measured the biomass and quality of 70-day-old ARs. Th2 and Th3 promoted root rot resistance of A. lancea. Th2, Th3 and Th4 all boosted AR quality: the concentration of the four major medicinal compounds in ARs (atractylon, atractylodin, hinesol and β-eudesmol) each increased 1.6- to 18.2-fold. Meanwhile, however, the yield of ARs decreased by 0.58- to 0.27-fold. Overall, Th3 dramatically increased the quality of ARs at a relatively low cost, namely lower yield, showing great potential for practical application. Our results showed selectivity between A. lancea and allochthonous Trichoderma isolates, indicating the importance of selecting specific microbial patches for herb cultivation.

Guanghui Chen, Lan Gao, Peiming Zheng, Yanhong Liu, Pan Li, Huifang Liu Department of Clinical Laboratory, Henan Provincial People′s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, People’s Republic of ChinaCorrespondence: Guanghui Chen, Department of Clinical Laboratory, Henan Provincial People′s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, No. 7 Weiwu Road Jinshui District, Zhengzhou, 450003, People’s Republic of China, Email chengguanghui1601@zzu.edu.cnPurpose: This study aims to analyze the distribution of human papillomavirus (HPV) genotypes and the associations of demographic characteristics with HPV infection among women with condyloma acuminatum (CA) in Henan Province of China.Methods: From January 2019 to October 2022, 702 women with CA were sampled for HPV subtypes and surveyed by questionnaire at Henan Provincial People′s Hospital. The HPV genotype was tested by flow-through hybridization after polymerase chain reaction (PCR).Results: The location of warts was mainly vulva. The age of the subjects was mainly distributed in the 20– 29-year-old, followed by 30– 39-year-old. The most common subtypes were HPV 6 (43.59%), 11 (24.93%), 16 (11.82%), 52 (7.83%), 58 (7.55%), 51 (7.26%), 61 (5.70%), 39 (5.56%), 18 (5.13%), and 54 (4.70%), our results also suggested that HPV 6 and 11 were the dominant genotypes in each age group. The infection of low-risk HPV (LR-HPV) (74.50%) and single HPV (47.01%) were the main categories. In terms of educational level, women with senior high school or above were inclined to infect single and pure-LR HPV. Unmarried status, sometimes or never condom use increased the chances of multiple, pure high-risk (HR) and mixed HPV infections. Women with multiple sex partners were more likely to cause multiple and mixed HPV infections.Conclusion: Our experimental data on the prevalence and subtype distribution of HPV in women with CA could provide valuable reference for preventing CA in Henan Province. The application of the nine-valent vaccine provides a broad prospect for female CA prevention.Keywords: human papillomaviruses, condyloma acuminatum, genetype distribution, prevalence, central China

Abstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. Methods We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. Results In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. Conclusion P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract

Lu Liu,1,&ast; Ling Zhou,1,&ast; Ling-Ling Wang,1 Peng-Dou Zheng,1 Feng-Qin Zhang,1 Zhen-Yu Mao,1 Huo-Jun Zhang,2 Hui-Guo Liu1 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui-Guo Liu; Huo-Jun Zhang, Email huiguol@163.com; hjzhang@whu.edu.cnAbstract: Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.Keywords: asthma, bronchial asthma, programmed cell death

The COVID-19 infection belongs to the category of "blight" in Traditional Chinese Medicine. The course of illness is generally about 7 days, and the recovery period is crucial for COVID-19 patients. This paper comprehensively summarized the application of Traditional Chinese Medicine nursing in the recovery period of novel coronavirus infection from the aspects of moxibustion, exercise therapy, Traditional Chinese Medicine emotional therapy, acupoint massage, diet nursing, etc. , so as to provide reference for further research. (新型冠状病毒感染属于中医“疫病”范畴, 病程一般约7 d, 恢复期对于患者来说至关重要。本文从艾灸、运动调护、中医情志疗法、穴位按摩、饮食护理等方面总结了中医护理在新型冠状病毒感染恢复期的应用, 为进一步研究提供参考。)

In order to promote the inheritance innovation and development of Traditional Chinese Medicine nursing, the establishment of Traditional Chinese Medicine nursing veteran expert experience inheritance system and sharing platform, enhance the confidence of Traditional Chinese Medicine nursing culture. This article shared the contents of the establishment, forms and achievements of "Zheng Ping Traditional Chinese Medicine Inheritance Studio", in order to provide reference for Traditional Chinese Medicine nursing inheritance management mode. (为推动中医护理传承创新与发展, 建立中医护理老专家经验传承体系和共享平台, 提升中医护理文化自信。本文从“郑萍中医护理传承工作室”的建立、传承的形式及传承的成果等内容进行分享, 以期为中医护理传承管理模式提供参考借鉴。)

This paper extracted transcripts of conversational dialogues with Traditional Chinese Medicine nursing master Zheng Ping, and summarized Zheng Ping’s working and learning experience and her thinking on inheritance of Traditional Chinese Medicine nursing, and provided reference for learning and inheriting valuable experience. (本文通过整理中医护理传承导师郑萍访谈录, 总结传承导师郑萍的工作体会、学习经历、对中医护理传承的思考等内容, 为传承人学习和继承郑萍导师宝贵护理经验提供参考。)

This paper reviewed the research literature of clinical status medicine in the past ten years, summarized the theory of clinical status medicine, and discusses the Traditional Chinese Medicine nursing based on this theory in the future nursing circle, aiming to provide new ways and new ideas for clinical Traditional Chinese Medicine nursing practice. (回顾近十年来临床状态医学的研究文献, 对临床状态医学的理论进行综述, 对未来护理领域可基于该理论开展的状态调护内容进行探讨, 旨在为临床中医护理实践提供新理论、新途径、新思路。)

Abstract Background Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an aggressive subtype, accounting for around 20% of all breast cancers. The development of HER2-targeted therapy has substantially improved patient outcomes. Nevertheless, the increasing rate of side effects and resistance to targeted drugs limit their efficacy in clinical practice. In this study, we designed and synthesized a new immunotoxin, 4D5Fv-PE25, which targets HER2-positive breast cancer, and evaluated its effectiveness in vitro and in vivo. Results The 4D5Fv-PE25 was expressed in high-density Escherichia coli (E. coli.) using the fermentor method and refined via hydrophobicity, ion exchange, and filtration chromatography, achieving a 56.06% recovery rate. Additionally, the semi-manufactured product with 96% purity was prepared into freeze-dried powder by the lyophilized process. Flow cytometry was used to detect the expression of HER2 in SK-BR-3, BT-474, MDA-MB-231, and MDA-MB-468 breast cancer cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method was used for cytotoxicity assay, and the half-maximal inhibitory concentration (IC50) of 4D5Fv-PE25 lyophilized products to HER2-positive cell line SK-BR-3 was 12.53 ng/mL. The 4D5Fv-PE25 was injected into xenograft tumor mice via the tail vein on the 1st, 4th, and 8th day, it indicated that the growth of tumor volume was effectively inhibited for 24 days, although the 4D5Fv-PE25 was metabolized within 60 min by measuring the release of 3 H-Thymidine radiation. Conclusion we succeeded in producing the 4D5Fv-PE25 freeze-dried powder using the prokaryotic expression method, and it could be employed as a potential drug for treating HER2-positive breast cancer. Graphical abstract

The classification of jade grade has always been a very critical part of the jade industry, and improving the accuracy of jade grade classification is of great significance to the sustainable development of the jade industry. The study constructs a mineral identification classification model based on Raman spectroscopy + PCA through Raman spectroscopy and PCA principal component analysis and analyzes the data of jade grades and constituents. The actual performance of this paper’s model is explored by comparing its effectiveness with other algorithmic models in jade classification and the accuracy of classification parameters. The model in this paper is feasible in classifying the four grades of Hetian jade (seed material, gobi material, shanliushui material, and shanmu material). Green dense jade’s main minerals are -quartz and a few other minerals, including albite, hematite, graphite, and tourmaline. The main compositions of the sample jade are SiO2, Al2O3, and K2O. The overall accuracy of this paper’s model in classifying Xinjiang Hotan jade grades is 97.9%, which is significantly higher than that of the KNN classification algorithm and SVM classification algorithm. The total accuracy of this paper’s model on each parameter of jade grade is 85, which is higher than the 60 of the KNN algorithm and the 62 of the SVM algorithm, and the classification accuracy grade is high.

This study divides eight indexes from three dimensions—the outer layer, middle layer, and inner layer—in order to evaluate the English teaching modes in colleges and universities. The evaluation is focused on the traditional English teaching method, the flipped classroom, and the blended English teaching method. An English teaching model assessment framework based on the entropy weight-cloud model is created by applying the cloud model to the English teaching model and using the entropy weight technique to establish the weights of each evaluation index. The comprehensive grade of each sample is computed using the subordination degree of each assessment index. A new teaching model is suggested based on the evaluation results, and the model is examined in terms of learners’ attitudes and learning effects in order to confirm the flexibility and benefits of the cloud model for the assessment of English teaching models. According to the data analysis, the three teaching modes’ values in the excellent grade are 0.001, 0.1502, and 0.3020. The comprehensive grade in the traditional teaching mode is poor, the comprehensive grade in the flipped teaching mode is medium, and the comprehensive grade in the blended teaching mode is good.

Most of the existing English online teaching platforms are just digital replicas of offline teaching, which cannot fully utilize the advantages of information technology. Based on the learning theory of constructivism, this paper builds the functional architecture of a personalized English interactive teaching platform and completes the design of the main functional modules. According to the quantitative results of the platform’s user proposition requirements, a matrix description method for English test papers is proposed, and an algorithm is designed to realize the automatic generation of test papers. Meanwhile, the resource recommendation mechanism of the English platform is optimized using a multilayer perceptual machine. Unstructured English learning resources are processed based on the word vector representation method, and for the problem of insufficient processing of nonlinear data in the DN-CBR model, multilayer training is carried out using the MLP to improve the perceptual degree of this part of the data, and the design goals are verified through the test of the teaching platform. The correlation coefficient between self-assessment difficulty and topic difficulty is 0.368, and the correlation coefficient between self-assessment difficulty and positive error is 0.163, indicating that there is a moderate correlation between learners’ self-assessment difficulty and the difficulty of the system topics and between learners’ self-assessment difficulty and positive error. The MLP-based pushed questions’ difficulty is adapted to the learner’s personalization level by dynamically revising it based on their learning process data.

The effect of milk fat globule (MFG) size and species (sheep versus cow) on the lipid and protein compositions of sheep and cow milks was studied. The MFGs in raw cow and sheep milks were separated into six significantly different-sized (1.5–5.5 μm) groups by a gravity-based separation method, and their fatty acids, their lipidomes and the protein compositions of their MFG membranes were determined. The proportions of polar lipids increased but glycoproteins decreased with decreasing MFG size in both sheep milk and cow milk; the fatty acid composition showed few differences among the MFG groups. The average size of each MFG group was comparable between sheep milk and cow milk. Sheep milk contained higher proportions of short-chain fatty acids, medium-chain fatty acids and sphingomyelin than cow milk in all MFG groups. The proportion of glycoproteins was higher in cow MFG membrane than in sheep MFG membrane. The results suggested that the lipid and protein compositions were markedly species and size dependent.

Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B, a major component of selectivity factor 1 (SL1), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B, in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.

Rui Zheng,1,&ast; Yaxian Jiang,1,&ast; Cheng Yan,2,&ast; Yikun Li,1 Xiaozhou Song,3 Pengcheng Zheng4 1Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Medical School, Kunming University of Science and Technology, The First People’s Hospital of Yunnan, Kunming, People’s Republic of China; 3Department of Infection Control, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 4Department of Pharmacy, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengcheng Zheng, Department of Pharmacy, The First People’s Hospital of Yunnan Province, No. 157 of Jingbi Road, Kunming, People’s Republic of China, Tel +86 013888116045, Email zpc1997@163.com Xiaozhou Song, Department of Infection Control, The First People’s Hospital of Yunnan Province, No. 157 of Jingbi Road, Kunming, People’s Republic of China, Tel +86 013888144965, Email 13888144965@163.comIntroduction: Ventilator-associated pneumonia (VAP) is an ICU (intensive care unit)-acquired pulmonary parenchymal infection that is complicated by mechanical ventilation and is associated with high morbidity and mortality. Klebsiella pneumoniae (KPN) is known to asymptomatically colonize the gastrointestinal tract and may increase the incidence of corresponding VAP. Our study aims were to investigate the exact origin of the carbapenem-resistant Klebsiella pneumoniae (CRKP) causing VAP in our patient.Methods: Various environmental samples, including the patient’s anal swab, were collected in order to find the source of the bacteria. Minimum inhibitory concentrations (MICs) for antimicrobial agents were determined according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI); resistant genes were detected by using PCR and sequencing; clone relationships were analyzed by using multilocus-sequence typing (MLST) and pulsed field gel electrophoresis (PFGE). The IAP values were obtained via urinary catheter.Results: One CRKP strain was detected in the patient’s anal swab; this strain was confirmed with the same gene type as the strain isolated from the sputum. We found that the patient’s intra-abdominal pressure (IAP) was 29.41, 27.06, 24.12, and 22.66 mmHg; the IAP was either equal to or above 12 mmHg, on the operation day and the following three days. Intra-abdominal hypertension (IAH) occurred during the patient’s hospitalization and was considered to be caused by the surgical procedure. Meanwhile, we found that there was a correlation between IAH and the detection of CRKP in the sputum. The findings suggested that his VAP was caused by intestinal colonial KPN, and not from the environment.Discussion: Our research illustrated that the ST11 KPC-2-producing strain colonized the intestinal tract and caused the development of VAP when the IAP was elevated. Routine screening for the intestinal carriage of CRKP, among patients in ICUs, can limit and prevent current and future outbreaks.Keywords: ventilator-associated pneumonia, intra-abdominal pressure, intra-abdominal hypertension, Klebsiella pneumoniae, healthcare-associated infection

In ecologically fragile areas of western and northwestern China, where coal mine water is reused as domestic water or discharged into surface water systems after treatment (the discharge concentration of fluoride (F^-) is less than 1.0 mg/L). In order to solve the disadvantages of adsorption technology such as complicated process, difficult operation and management and unstable effluent quality, an experiment was carried out to remove fluoride by complexing-induction fluoride removal agent. The effects of dosage, reaction time, pH value and turbidity on fluoride removal were investigated, and the defluorination mechanism was analyzed. The results showed that the complexing-induction fluoride removal agent could capture ionic fluoride in mine water through the complex adsorption and chemical induction, and finally form blended precipitates to remove fluoride. When the dosage of the fluoride removal agent was 45 mg/L, reaction time was 12 min, pH value was 8~9 and the turbidity of raw water was less than 100 NTU, the concentration of fluoride ions in the simulateds mine water could be reduced from 5 mg/L to less than 1.0 mg/L. Carbonate ions affected fluoride removal significantly, followed by sulfate ions, while chloride ions had no obvious influence. In the continuous experiment of fluoride removal from mine water, the concentration of fluoride in the effluent was 0.75~0.90 mg/L, and the turbidity was 8.2~10.0 NTU.

Extracellular vesicles (EVs) from antler reserve mesenchymal (RM) cells play an important role in the paracrine regulation during rapid growth of antler without forming a tumor; therefore, RM-EVs become novel materials for anti-tumor studies, such as osteosarcoma treatment. However, the problem of low production of RM-EVs in traditional 2D culture limits its mechanism research and application. In this study, we established an optimal 3D culture system for antler RM cells to produce EVs (3D-RM-EVs). Morphology and property of harvested 3D-RM-EVs were normal compared with EVs from conventional 2D culture, and the miRNA profile in them was basically the same through transcriptome sequencing analysis. Based on the same number of RM cells, the volume of the culture medium collected by 3D cultural system concentrated nearly 30 times, making it more convenient for subsequent purification. In addition, EVs were harvested 30 times in 3D cultural system, greatly increasing the total amount of EVs (harvested a total of 2–3 times in 2D culture). Although 3D-RM-EVs had a limited inhibitory effect on the proliferation of K7M2 cells, the inhibition effect of 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) were more significant than that of positive drug group alone ( P < 0.05). Furthermore, in vivo studies showed that 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) had the most significant tumor inhibition effect, with decreased tumor size, and could slow down body weight loss compared with Ifosfamide + Etoposide (IFO + ET) group. These results demonstrated that 3D-RM-EVs were efficiently prepared from antler RM cells and were effective as drug vehicles for the treatment of osteosarcoma.

Photonic convolution processing units are the core components of photonic neural networks (PNNs). Traditionally, for an N × N photonic convolution processing unit, it typically requires O(N2) or O(Nlog2N) cascaded photonic devices, which leads to larger sizes and lower density. Therefore, nanophotonic neural networks (N-PNN) with high density are highly attractive. In this work, we propose an ultra-high density and nonvolatile N-PNN scheme, requiring only a compact photonic device to represent all weight values in the N × N convolution kernel, which results in a computational density of more than 5 petaflop operations per second per square millimeter (POPS/mm2) under ideal conditions. The footprints of the proposed 2 × 2 and 3 × 3 nanophotonic convolution processing units are only 4 × 4 μm2 and 6 × 6 μm2, respectively. Moreover, based on these two types of units, the N-PNN achieves image classification and recognition capabilities comparable to traditional computers. In addition, Owing to its lower insertion loss, our approach holds great significance for the scalability and on-chip integration of large-scale N-PNNs. This facilitated the integration of N-PNNs with existing electronic systems.