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Objective: Obesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate. Methods: To determine if the observed microbiota changes are required for 10,12 CLA-mediated weight loss, adult male mice with diet-induced obesity were given broad-spectrum antibiotics (ABX) to perturb the microbiota prior to and during 10,12 CLA-mediated weight loss. Conversely, to determine whether gut microbes were sufficient to induce weight loss, conventionally-raised and germ-free mice were transplanted with cecal contents from mice that had undergone weight loss by 10,12 CLA supplementation. Results: While body weight was minimally modulated by ABX-mediated perturbation of gut bacterial populations, adult male mice given ABX were more resistant to the increased energy expenditure and fat loss that are induced by 10,12 CLA supplementation. Transplanting cecal contents from donor mice losing weight due to oral 10,12 CLA consumption into conventional or germ-free mice led to improved glucose metabolism with increased butyrate production. Conclusions: These data suggest a critical role for the microbiota in diet-modulated changes in energy balance and glucose metabolism, and distinguish the metabolic effects of orally delivered 10,12 CLA from cecal transplantation of the resulting microbiota.

Jing Wang,1,2,* Yi Duan,2,* Liangrong Geng,2 Xiaoyu Li,3 Shujin Yue,2 Hongxia Liu2 1Department of Nursing, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Nursing, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Center for Treatment of Undiagnosed Diseases, the First Affiliated Hospital of Nanchang University, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shujin Yue, Beijing University of Chinese Medicine, No. 11 North 3rd Ring East Road, Chao-Yang District, Beijing, 100029, People’s Republic of China, Email yueliang874@126.comPurpose: To (1) investigate the changes in 5 domains (lack of family support, impact on finance, impact on daily schedule, impact on health, and self-esteem) of family caregiver (FC) burden and overall burden for first diagnosed colorectal cancer; (2) exploring changes in FC burden for colorectal cancer patients over time and analyze the trajectory and sub-trajectories of FC burden; and (3) identify the FC‐related and patient‐related factors most associated with the overall FC burden and each of its sub-trajectories.Patients and methods: This study is a descriptive longitudinal study. A convenience sampling method was used to recruit patients with colorectal cancer and their primary FCs from seven hospitals.Results: A total of 185 pairs of first diagnosed colorectal cancer patient and their FC were investigated for 4 times. The results reveal the overall burden and 5 domains of burden showed a trend of increasing first and then decreasing, and the burden was the heaviest at the time in the middle of chemotherapy. In the course of time, the aspect that caused the greatest amount of burden on average transitioned from the “effect on daily schedule” (range= 3.3 and 3.9) to the “effect on finances” (range= 3.1 to 3.4).Conclusion: Almost 88% of FCs have a either a moderate or a high level of burden. The quality of life of patients and the self-efficacy, social support and care ability of FCs have a great impact on the overall FC burden and each sub-trajectory.Keywords: care burden, colorectal cancer, family caregiver, longitudinal study, trajectories

Xiaomin Ren,1 Dingqun Bai,2 Yuan Zhang,3 Haidan Lin,2 Shu Zhang,2 Danyang Li,1 Hui Wei,1 Shouwei Yue1 1Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Physical Medicine & Rehabilitation, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Shouwei Yue; Hui Wei, Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China, Tel +18560086655 ; +18560083563, Fax +531 82166115, Email shouweiy@sdu.edu.cn; 83926275@qq.comBackground and Purpose: Epidemiological studies on low back pain in residents living in mountainous areas are scarce. The study was aimed at investigating the prevalence and associated factors of low back pain in Chongqing, relatively impoverished mountainous areas of China.Materials and Methods: This was a cross-sectional study conducted at selected community or village health service centers in Chongqing over a 2-month period (May 2021 to June 2021), which included adults of Chongqing aged > 18 years with or without low back pain (N=1820) chosen by stratified, cluster-sampling. Associated factors of low back pain including sociodemographic characteristics, lifestyle, and occupational features were collected, along with medical history, Oswestry Disability Questionnaire (ODI), and Numerical Rating Scale (NRS) of patients with low back pain, and carried out for at least 20 minutes per respondent. Univariate and multivariate logistic regression models were utilized for statistical analysis.Results: Overall, 30.5% of 1704 respondents presented with low back pain, with 26.3% living in flat areas and 35.6% in mountainous areas. The associated factors of low back pain were mountainous area residence (OR 1.4, 95% CI 1.1– 1.8), advanced age (OR 1.8, 95% CI 1.3– 2.5 for those aged 45– 59 years, OR 2.3, 95% CI 1.6– 3.4 for those aged 60– 74 years, and OR 2.1, 95% CI 1.2– 3.6 for those aged ≥ 75 years), married or remarried (OR 1.9, 95% CI 1.1– 3.2), divorced or widowed (OR 2.7, 95% CI 14– 5.4), moderate labor intensity (OR 1.4, 95% CI 1.1– 1.8), frequent stoop (OR 1.6, 95% CI 1.1– 2.4), and depressed mood (OR 1.6, 95% CI 1.2– 2.1). Residents in the mountainous areas had a higher score on Oswestry Disability Questionnaire (8.3 [SD 6.3] vs 6.2 [SD 4.3]) than those in flat areas.Conclusion: Mountainous areas in Chongqing had higher prevalence of low back pain as 35.6%, compared with 26.3% in flat areas, with more severe dysfunction in low back pain patients. Multifactorial analysis found that the factors associated with low back pain in Chongqing residents included mountain residence, labor intensity, stoop, psychological factors and frequency of exercise.Keywords: low back pain, prevalence, associated factors, China

Yufeng Wang,1,2,* Xueying Huang,1,* Suru Yue,1 Jie Liu,1 Shasha Li,1 Huan Ma,1 Liren Hu,1 Jiayuan Wu1,2 1Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China; 2Collaborative Innovation Engineering Technology Research Center of Clinical Medical Big Data Cloud Service in Medical Consortium of West Guangdong Province, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiayuan Wu Email wujiay@gdmu.edu.cnBackground: Migraine is a common disorder of the nervous system in China, imposing heavy burdens on individual and societies. Optimal healthcare planning requires understanding the magnitude and changing the trend of migraine incidence in China. However, the secular trend of migraine incidence in China remains unclear.Methods: Data were collected from the Global Burden of Disease Study 2019 in China from 1990 to 2019 to investigate changes in the incidence rate of migraine. The average annual percent change and the relative risk were calculated using the joinpoint regression model and the age–period–cohort model, respectively.Results: From 1990 to 2019, the age-standardized incidence rates of migraine in China increased by 0.26% (95% CI: 0.22 to 0.31) and 0.23% (95% CI: 0.19 to 0.28) per year in males and females, respectively. Age effects exerted the most significant impact on migraine incidence. Period effects showed a slightly decreasing trend in the incidence of migraine. In terms of cohort effects, people born after the 1960s presented a higher risk of migraine as compared with the total cohort, with the incidence risk of migraine increasing with birth cohorts.Conclusion: Migraine incidence shows an overall increasing trend in China, with a significant gender difference. A comprehensive understanding of the risk characteristics and disease pattern of migraine could allow the early detection of persons with a high risk of developing migraine and promote the development of timely intervention measures to relieve this burden effectively.Keywords: migraine, incidence, secular trend, joinpoint regression analysis, age–period–cohort model

Shuwen Yue,1,* Ning Xue,2,* Honglei Li,3 Zhen Chen,1 Baosheng Huang,4 Xing Wang1 1Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Department of Acupuncture, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Pharmacy, Kangda College of Nanjing Medical University, Lianyungang, People’s Republic of China; 4Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing WangChina Pharmaceutical University, Nanjing, Jiangsu 211199, People’s Republic of ChinaEmail star10000@sina.comBaosheng HuangSir Run Run Hospital, Nanjing Medical University, No. 101, Longmiandadao, Jiangning District, Nanjing, Jiangsu 211166, People’s Republic of ChinaEmail labskcpu@sina.comAim: Renal injury induced by diabetes is reported to be associated with inflammation. Isomangiferin (ISO), a xanthone C-glucoside from the Cyclopia subfamily, exhibits many pharmacological properties. This study aimed to evaluate the protection of ISO against renal damage in diabetic mice.Methods: Serum glucose, insulin, uric acid, creatinine, total cholesterol (TC), triglyceride (TG), and inflammatory cytokines in serum and the kidney of db/db diabetes model mice were detected. The components of high mobility group protein B1 (HMGB1)/NACHT leucine-rich repeat- and PYD-containing 3 (NLRP3)/nuclear factor kappa-B (NF-κB) pathway in the kidney were detected by Western blot and immunohistochemical analysis.Results: ISO improved lipid profile and glucose tolerance, and inhibited the production of inflammatory cytokines in a db/db model mice. Moreover, ISO decreased biochemical indexes in the serum and inhibited the activation of HMGB1/NLRP3/NF-κB signaling in the kidney of db/db model mice.Conclusion: ISO provides protection against renal injury via inhibiting HMGB1/NLRP3/NF-κB signaling in a diabetic mouse model.Keywords: isomangiferin, renal injury, inflammation, HMGB1/NLRP3/NF-κB, diabetics

Suebsarn Ruksakulpiwat,1,2 Zhaojun Liu,1 Shihong Yue,1 Yuying Fan1,2 1The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2College of Nursing, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Yuying FanThe Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; College of Nursing, Harbin Medical University, 157 Baojian Road, Nangang Distinct, Harbin 150086, Heilongjiang Province, People’s Republic of ChinaTel +86 13603630368Email fanfanfensituan@126.comPurpose: To examine the association and the mediating effect among medication beliefs, perception of illness, and medication adherence in ischemic stroke patients.Patients and Methods: This is a cross-sectional study, 306 ischemic stroke patients recruited from The Second Affiliated Hospital of Harbin Medical University, China between June 2018 and October 2018. The Beliefs about Medications Questionnaire (BMQ) was used to assess a patient’s beliefs about medication. The Brief Illness Perceptions Questionnaire (BIPQ) was used to rapidly determine the cognitive and emotional representation of ischemic stroke. Self-reported adherence was assessed using the Medication Adherence Report Scale (MARS). Logistic regression analysis, Pearson correlations, and mediation analysis were used to evaluate the association and mediating effects among medication beliefs, perception of illness, and medication adherence.Results: Overall, 220 (65.48%) participants were non-adherent to their ischemic stroke medications. Non-adherent patients had greater stroke severity (p = 0.031) compared to adherent patients. After adjusting for demographic characteristics, specific concern (odds ratio [OR]: 0.652, 95% confidence interval [CI]: 0.431 to 0.987, p-value [P] = 0.043), and the perception of illness (overall score) (OR: 0.964, 95% CI: 0.944 to 0.985, P = 0.001) were significantly associated with medication adherence in ischemic stroke patients. The mediation analysis showed the significant indirect effects of specific concern, general overuse, and general harm. It suggested that some impacts of medication beliefs have been mediated on medication adherence.Conclusion: Perceived concern about adverse effects of medicines and perception of illness have an influential impact on self-reported medication adherence in ischemic stroke patients. To enhance adherence, patients’ beliefs about medication and perceptions of their disease should be reconsidered. Future work should investigate interventions to influence patient adherence by addressing concerns about their ischemic stroke medications and the perception of the disease.Keywords: ischemic stroke patients, medication beliefs, perception of illness, medication adherence

Jingyang Wu,1 Yifan Zhong,1 Song Yue,1 Peng Guan,2 Guisen Zhang,3 Lei Liu,1 Lei Chen11Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, People’s Republic of China; 3Department of Ophthalmology, Hohhot Chao Ju Eye Hospital, Hohhot 010000, People’s Republic of ChinaPurpose: Abnormal levels of lipid accumulation product (LAP) have been associated with risk of cardiovascular disease and diabetes. However, it is not clear whether LAP index is associated with diabetic retinopathy (DR). We investigated the association between LAP index and DR in Chinese adults with diabetes.Patients and methods: We included 427 Chinese patients with type 2 diabetes aged 18-year over who participated in a community-based cross-sectional study in Shenyang. DR was addressed on retinal photographs graded using the modified Airlie House classification. LAP was defined as (waist circumference [cm]–65) × (triglycerides [mmol/L]) in men, and (waist circumference [cm]–58) × (triglycerides [mmol/L]) in women and analyzed continuously (per SD change) and categorically (quartile 1, 50).Results: Prevalence of DR among the study population was 17.8%. The mean level of LAP was 52.96±44.01. Compared to quartile 1 level, both quartile 2 and 3 levels were associated with DR with multivariable odds ratio (95% CI) of 0.23 (0.12–0.46) and 0.27 (0.14–0.54), respectively. These associations persisted when LAP was analyzed continuously (0.57 [0.35–0.92]).Conclusion: Higher central lipid accumulation in Chinese diabetics is related to the lower risk of DR, suggesting that LAP may be useful for identifying type 2 diabetes mellitus patients who are at risk for DR.Keywords: diabetic retinopathy, lipid accumulation product, diabetes

The urban three-dimensional (3-D) model, which can truly and vividly express the 3-D spatial information of ground objects, was an essential link in the process of smart city construction. The backpack 3-D laser scanning systems had gradually become an important technical means to build urban 3-D models because of their high efficiency and high fineness. In this paper, the error source of backpack point cloud data was analysed based on the composition of backpack 3-D laser scanning system. The distribution of point cloud error was statistically analysed by designing experiments. It was found that there was a systematic error in the backpack 3-D laser scanning point cloud. There were many factors influencing the system errors and they were superimposed on each other. In order to solve this problem, an error compensation model with additional system parameters based on a multiple linear regression algorithm was constructed. The results showed that this model can weaken the influence of system errors on the backpack point cloud, effectively improve the accuracy of the backpack point cloud, and provide reliable point cloud data for subsequent processing of the building point cloud. [ABSTRACT FROM AUTHOR]

Although pretransplant diabetes is a risk factor for mortality post-liver transplant, the underlying mechanism has not been fully defined. In a murine liver partial warm ischemia model, we addressed the question of how diabetes/hyperglycemia impacted tissue inflammatory injuries against ischemia reperfusion (IR), focusing on the advanced glycation endproduct (AGE) and its receptor (RAGE) pathway. Our results showed that hepatocellular injury was exacerbated in streptozotocin-induced diabetic mice against IR, in association with hyper-inflammatory immune activation in livers. Serum levels of AGEs, but not HMGB1, were increased in diabetic mice in response to liver IR. Both RAGE antagonist peptides and small interfering RNA alleviated liver injuries and inhibited inflammatory immune activation against IR in diabetic, but not normal, mice. Kupffer cells (KCs)/macrophages, but not hepatocytes, from diabetic mice expressed significantly higher levels of RAGE, leading to their hyper-inflammatory responsiveness to both TLR ligands and AGEs. In vitro, hyperglycemia increased macrophage RAGE expression and enhanced their TLR responses. Our results demonstrated that activation of the AGE-RAGE signaling pathway in KCs was responsible for hyper-inflammatory immune responses and exacerbated hepatocellular injuries in diabetic/hyperglycemic hosts against liver IR.

Although the roles of the metabolic stress in organ ischemia-reperfusion injury (IRI) have been well recognized, the question of whether and how these stress responses regulate innate immune activation against IR remains unclear. In a murine liver partial warm ischemia mode, we showed that prolonged ischemia triggered endoplasmic reticulum (ER) stress response, particularly, the activating transcription factor 6 (ATF6) branch, in liver Kupffer cells (KCs) and altered their responsiveness against Toll-like receptor (TLR) stimulation. Ischemia-primed cells increased pro-, but decreased anti-, inflammatory cytokine productions. Alleviation of ER stress in vivo by small chemical chaperon 4-phenylbutyrate or ATF6 small interfering RNA (siRNA) diminished the pro-inflammatory priming effect of ischemia in KCs, leading to the inhibition of liver immune response against IR and protection of livers from IRI. In vitro, ATF6 siRNA abrogated the ER stress-mediated pro-inflammatory enhancement of macrophage TLR4 response, by restricting NF-κB and restoring Akt activations. Thus, ischemia primes liver innate immune cells by ATF6-mediated ER stress response. The IR-induced metabolic stress and TLR activation function in synergy to activate tissue inflammatory immune response.

The rapid and accurate differentiation of Angelica sinensis and Levisticum officinale is a significant challenge in the quality control of traditional Chinese medicine. Angelica sinensis and Levisticum officinale are different genera of the same family. Due to their similar appearances and partially shared chemical components, unscrupulous traders often sell counterfeit Levisticum officinale as Angelica sinensis to make exorbitant profits. In this study, a fast and easy method of ultrasonic extraction and nebulization in real-time/carbon fiber ionization mass spectrometry (UENRT/CFI-MS) was introduced for the swift discrimination of these two easily confused traditional Chinese medicines. UENRT/CFI-MS primarily consists of an online extraction and nebulization unit, an ionization unit. The online extraction and nebulization unit employ an ultrasonic nebulizer chip for real-time sample extraction and nebulization. The ionization unit comprises a 10 mm long carbon fiber rod nested in a metal tube, achieving ionization through the application of a 3 kV high voltage, and the auxiliary solvent (methanol) is continuously supplied to the carbon fiber at a rate of 5 μL/min. Slices of Angelica sinensis and Levisticum officinale from different origins with similar size, appearance, and quality (diameter less than 16 mm, thickness not exceeding 0.5 cm) were selected and placed directly on the nebulizer chip. For each analysis, 200 μL methanol was continuously added using a pipette. When the nebulizer was activated, the lower end of the nebulizer chip generated a continuous spray of tiny droplets towards the carbon fiber tip for several seconds, which were then ionized before entering the mass spectrometer for detection. This device integrates online ultrasonic extraction, nebulization, and carbon fiber ionization technologies, enabling real-time analysis of complex samples without cumbersome pretreatment. By applying this technique, a characteristic ion peak of m/z 496 is uniquely identified in Levisticum officinale, serving as a distinctive marker for differentiation of Angelica sinensis and Levisticum officinale. Subsequently, comparative analysis was conducted using sample extracts on electrospray ionization mass spectrometry (ESI-MS) and carbon fiber ionization mass spectrometry (CFI-MS). These experimental results showed that CFI-MS exhibits superior selectivity and efficiency in detecting the m/z 496 characteristic peak, which is not observable in ESI-MS analysis. This finding highlights the unique ability of carbon fiber ionization to selectively detect certain compounds. The UENRT/CFI-MS technique was applied for the direct analysis of Angelica sinensis and Levisticum officinale, and can obtain the analysis results in just a few seconds. A distinctive ion of m/z 496 is detected in Levisticum officinale, facilitating swift discrimination between Angelica sinensis and Levisticum officinale. However, further research is needed to elucidate the structure of the m/z 496 characteristic peak. Additionally, the method’s applicability to a wider range of herbal medicines and its performance in more complex matrices should be investigated. This method is expected to play a role in traditional Chinese medicine identification.

Abstract Pompe disease, a severe lysosomal storage disorder, is marked by heart problems, muscle weakness, and respiratory difficulties. This study aimed to identify novel markers for infantile-onset Pompe disease by analyzing key genes and immune cells infiltrating affected skeletal muscles, building on existing research linking its progression to the immune cell infiltration. The datasets GSE38680 and GSE159062 were downloaded and differential expression genes (DEGs) were identified. Potential markers were screened using support vector machine recursive feature elimination (SVM-RFE) analysis and least absolute shrinkage and selection operator (LASSO) regression models. To analyze DEGs and immune processes, 22 immune cell types in affected tissues were examined using CIBERSORT. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment in the calcium signaling pathway, phosphatidylinositol signaling system, ubiquitin-mediated proteolysis and JAK-STAT signaling pathway. Machine learning identified GPNMB, CALML6 and TRIM7 as key genes. Immune cell infiltration analysis showed that the expression levels of the above three genes were closely related to immune cells in our target population under study, including T cells regulatory (Tregs), monocytes, macrophages M0, resting and activated dendritic cells, naive and memory B cells. Overall, our study results may provide new clues for exploring markers related to Pompe disease by highlighting key genes and their relationship with immune infiltration, offering insights into the disease’s development. However, previous studies have shown limited evidence of significant immune cell infiltration in muscle biopsies from Pompe patients, and this lack of direct evidence necessitates further investigation and experimental validation in laboratory settings to confirm these associations.

Abstract Background Observational studies have shown a link between autoimmune diseases and schizophrenia, with conflicting conclusions. Due to the existence of confounding factors, the causal link between autoimmune diseases and schizophrenia is still unknown. Method We conducted a comprehensive Mendelian randomization (MR) analysis of schizophrenia and ten common autoimmune diseases in individuals of European descent using genome-wide association studies (GWASs). To evaluate the relationships between autoimmune diseases and schizophrenia, inverse variance weighted, MR-RAPS, Bayesian weighted MR, constrained maximum likelihood, debiased IVW, MR-Egger, and weighted median were utilized. Several sensitivity analyses were performed to ensure the reliability of the study's results. Results Our findings reveal that genetically predicted ankylosing spondylitis is related to an increased risk of schizophrenia, whereas celiac disease, type 1 diabetes, and systemic lupus erythematosus are associated with a lower risk of schizophrenia. In the reverse MR analysis, our study indicated that genetically predicted schizophrenia is linked to higher risks of ankylosing spondylitis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, and psoriasis. Neither multiple sclerosis nor rheumatoid arthritis have been linked to schizophrenia, and vice versa. Conclusion Despite contradicting some other observational reports, this study showed support for a causal link between autoimmune diseases and schizophrenia. To gain a better understanding of the mechanisms underlying the development of immune-mediated schizophrenia, additional research is required to identify potential mechanisms identified in observational studies.

Abstract Immune checkpoint blockade (ICB) therapy has emerged as a new therapeutic paradigm for a variety of advanced cancers, but wide clinical application is hindered by low response rate. Here we use a peptide-based, biomimetic, self-assembly strategy to generate a nanoparticle, TPM1, for binding PD-L1 on tumour cell surface. Upon binding with PD-L1, TPM1 transforms into fibrillar networks in situ to facilitate the aggregation of both bound and unbound PD-L1, thereby resulting in the blockade of the PD-1/PD-L1 pathway. Characterizations of TPM1 manifest a prolonged retention in tumour ( > 7 days) and anti-cancer effects associated with reinvigorating CD8+ T cells in multiple mice tumour models. Our results thus hint TPM1 as a potential strategy for enhancing the ICB efficacy.

This study intends to explore the extraction process, physical and chemical properties, antioxidant and hypoglycemic activities of polysaccharides from wild bitter melon (WBM). Using the peel of fresh WBM fruit as raw material, based on the single factor experimental results, the liquid-to-material ratio, ultrasonic time and ultrasonic power in the ultrasound-assisted extraction (UAE) process were optimized by Box-Behnken response surface. Two polysaccharide components of WBP50 and WBP75 were obtained through UAE of the optimal conditions and gradient alcohol precipitation, and their physical and chemical properties, in vitro antioxidant and hypoglycemic abilities were evaluated. The results showed that: under the conditions of liquid-to-material ratio of 16 mL/g, ultrasonic time of 16 min, and ultrasonic power of 312 W, the actual yield of crude WBM polysaccharide (WBP) was 8.33%±0.13%. The total sugar, protein, total phenols, total flavonoids, and uronic acid contents of WBP50 and WBP75 were 76.73%/73.38%, 4.78%/0.35%, 0.36%/0.25%, 2.06%/0.86% and 72.85%/49.58%, respectively. The average molecular weights were 27.59 kDa and 23.20 kDa, respectively. WBPs were mainly composed of galacturonic acid, galactose, rhamnose, arabinose, and glucose. The DPPH, ABTS+ and hydroxyl radicals scavenging abilities of WBP50 and WBP75 were 11.28/11.40 μg Trolox/mg, 40.87/44.42 μg Trolox/mg, and 52.47/99.89 U/mg, respectively. Regarding hypoglycemic ability, both WBPs had certain α-amylase inhibitory ability and strong α-glucosidase inhibitory ability. The α-glucosidase inhibition rate of WBP50 and WBP75 reached 93.34%±1.11% and 79.04%±0.76% at a concentration of 750 μg/mL. The UAE of WBP has the advantages of time saving, convenience, high efficiency and low energy consumption, and the extracted WBPs have natural antioxidant and hypoglycemic functional activities. This study lays the foundation for future structural analysis and functional mechanism research of WBPs and provides theoretical references for developing hypoglycemic products and high-value utilization of WBPs.

Ya-Ya Bai,1 Rui Tian,1 Yan Qian,2 Qiao Zhang,1 Chong-Bo Zhao,1 Yong-Gang Yan,1 Li Zhang,3 Shi-Jun Yue,4 Yu-Ping Tang1 1Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 2Suzhou Institute for Drug Control, Suzhou, Jiangsu Province, 215000, People’s Republic of China; 3Hanlin College, Nanjing University of Chinese Medicine, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 4International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, 050200, People’s Republic of ChinaCorrespondence: Qiao Zhang, Shaanxi University of Chinese Medicine, Shiji Avenue, Xi Xian New District, Xi’an, 712046, People’s Republic of China, Tel +86-15895973680, Fax: +86-02938185061, Email 18700081184@163.comBackground: Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown.Objective: This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics.Methods: Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites.Results: Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect.Conclusion: PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application. Keywords: gut microbiota, metabolomics, wine steaming, diarrhea, rhubarb

Abstract Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.

Abstract Unravelling abrupt alterations in the gut microbiota of wild species associated with nutritional stress is imperative but challenging for wildlife conservation. This study assessed the nutritional status of wild red deer during winter on the basis of changes in faecal nitrogen (FN) and urea nitrogen/creatinine (UN: C) levels and identified gut microbes associated with nutritional status via nutritional control experiments and metagenomic sequencing. The FN of wild red deer in winter 2022 was significantly lower than that in winter 2021 (p

Abstract There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. Graphical Abstract

Abstract Background The current review aims to explore the evidence regarding the effectiveness of mandibular advancement orthodontic appliances with maxillary expansion device in treating pediatric Obstructive Sleep Apnea (OSA). Materials and methods A systematic literature search was conducted across PubMed, Cochrane Central, Web of Science, Embase, Scopus databases, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and Wanfang. The research involved children and adolescents (under 16 years old) who received mandibular advancement and maxillary expansion functional orthopedic appliances for OSA treatment. We performed narrative reviews and subsequently amalgamated the findings from the studies. Results Six articles were included for review. Although a small number of studies were included, the research suggested the potential advantages of mandibular advancement for children with OSA. Following treatment, there was a decrease in AHI/RDI, an improvement in sleep quality, and the increase in oxygen saturation. Conclusions The limited quantity and quality of existing studies necessitate caution when drawing conclusions about the effectiveness of mandibular advancement and maxillary expansion for OSA. In the future, larger and well-designed randomized controlled trials (RCTs) are needed to provide more robust evidence. Patients should be carefully selected, and their orthodontic indications should be thoroughly evaluated before inclusion in such trials.We encourage researchers to design studies that monitor patients over several years to provide a comprehensive understanding of the long-term effectiveness. Trial registration This study was registered in PROSPERO(CRD42023480407) on November 20, 2023.

Mpox is a zoonotic disease caused by the monkeypox virus (MPXV). Diagnosing and treating the disease has become a global health concern requiring close attention to its spread to non-endemic regions. Clinical diagnosis is based on laboratory test results. Conventional detection techniques include real-time quantitative polymerase chain reaction (qPCR), genome sequencing, antigen and antibody identification, and virus isolation. Nevertheless, these methods fall short of rapidly and efficiently identifying MPXV, as they require specialized training, specific laboratory environments, and professional-grade equipment. Emerging technologies offer complementary advantages to meet diverse diagnostic needs, including various point-of-care testing (POCT) approaches and integrating biosensors with rapid detection techniques. This review discusses prospective future research avenues for MPXV detection, examining the advances and challenges of various detection techniques which may contribute to the ongoing elimination of mpox human-to-human transmission and serves as a reference for developing effective prevention and control strategies.

Based on the oil and gas exploration in western depression of the Qaidam Basin, NW China, combined with the geochemical, seismic, logging and drilling data, the basic geological conditions, oil and gas distribution characteristics, reservoir-forming dynamics, and hydrocarbon accumulation model of the Paleogene whole petroleum system (WPS) in the western depression of the Qaidam Basin are systematically studied. A globally unique ultra-thick mountain-style WPS is found in the western depression of the Qaidam Basin. Around the source rocks of the upper member of the Paleogene Lower Ganchaigou Formation, the structural reservoir, lithological reservoir, shale oil and shale gas are laterally distributed in an orderly manner and vertically overlapped from the edge to the central part of the lake basin. The Paleogene WPS in the western depression of the Qaidam Basin is believed unique in three aspects. First, the source rocks with low organic matter abundance are characterized by low carbon and rich hydrogen, showing a strong hydrocarbon generating capacity per unit mass of organic carbon. Second, the saline lake basinal deposits are ultra-thick, with mixed deposits dominating the center of the depression, and strong vertical and lateral heterogeneity of lithofacies and storage spaces. Third, the strong transformation induced by strike-slip compression during the Himalayan resulted in the heterogeneous enrichment of oil and gas in the mountain-style WPS. As a result of the coordinated evolution of source-reservoir-caprock assemblage and conducting system, the Paleogene WPS has the characteristics of “whole process” hydrocarbon generation of source rocks which are low-carbon and hydrogen-rich, “whole depression” ultra-thick reservoir sedimentation, “all direction” hydrocarbon adjustment by strike-slip compressional fault, and “whole succession” distribution of conventional and unconventional oil and gas. Due to the severe Himalayan tectonic movement, the western depression of the Qaidam Basin evolved from depression to uplift. Shale oil is widely distributed in the central lacustrine basin. In the sedimentary system deeper than 2 000 m, oil and gas are continuous in the laminated limy-dolomites within the source rocks and the alga limestones neighboring the source kitchen, with intercrystalline pores, lamina fractures in dolomites and fault-dissolution bodies serving as the effective storage space. All these findings are helpful to supplement and expand the WPS theory in the continental lake basins in China, and provide theoretical guidance and technical support for oil and gas exploration in the Qaidam Basin.

Abstract Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention. One emerging machine learning paradigm that addresses this concern is federated learning (FL). FL enables multiple entities to collaboratively build machine learning models while preserving data privacy and security. In this study, we present a multicenter BCa magnetic resonance imaging (MRI) dataset. The dataset comprises 275 three-dimensional bladder T2-weighted MRI scans collected from four medical centers, and each scan includes diagnostic pathological labels for muscle invasion and pixel-level annotations of tumor contours. Four FL methods are used to assess the baseline of the dataset for both the task of diagnosing muscle-invasive bladder cancer and automatic bladder tumor lesion segmentation.

Abstract YTHDC1, a reader of N6-methyladenosine (m6A) modifications on RNA, is posited to exert significant influence over RNA metabolism. Despite its recognized importance, the precise function and underlying mechanisms of YTHDC1 in the preservation of normal hematopoietic stem cell (HSCs) homeostasis remain elusive. Here, we investigated the role of YTHDC1 in normal hematopoiesis and HSCs maintenance in vivo. Utilizing conditional Ythdc1 knockout mice and Ythdc1/Mettl3 double knockout mice, we demonstrated that YTHDC1 is required for HSCs maintenance and self-renewal by regulating microRNA maturation. YTHDC1 deficiency resulted in HSCs apoptosis. Furthermore, we uncovered that YTHDC1 interacts with HP1BP3, a nuclear RNA binding protein involved in microRNA maturation. Deletion of YTHDC1 brought about significant alterations in microRNA levels. However, over-expression of mir-125b, mir-99b, and let-7e partially rescued the functional defect of YTHDC1-null HSCs. Taken together, these findings indicated that the nuclear protein YTHDC1-HP1BP3-microRNA maturation axis is essential for the long-term maintenance of HSCs.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract Background With the evolution of disease patterns and the continuous pursuit of persons for high-quality nursing services, new nurses are the reserve talents of the nursing team and shoulder a major mission. However, due to their low work performance and high turnover rate, this is not conducive to the stable development of nursing teams, and it is urgent to solve this problem. The purpose of this study was to explore the effect of work readiness on the work performance of new nurses, focusing on the mediating role of organizational justice and professional identity. Method A cross-sectional design was employed. Using convenience sampling methods, 607 new nurses were surveyed in 5 hospitals in Henan Province, China, from January to February 2023. Data were collected using demographic characteristics questionnaire, the Work Performance Scale, the Work Readiness Scale for Graduate Nurses, the Organizational Justice Scale, and the Professional Identity Rating Scale for Nurses. AMOS 26.0 was used for model drawing and mediation path testing, and SPSS 25.0 was used for data analysis. Results The mediation model shows a good fit (χ2 /df = 2.747, CFI = 0.987, GFI = 0.948, AGFI = 0.926, TLI = 0.984, IFI = 0.987, and RMSEA = 0.054). In this study, we found professional identity is a mediating variable between work readiness and the work performance of new nurses (β = 0.113, P

Abstract In this paper, a nodal detection method for the detection and optimization of barrel helix offsets is proposed. The barrel used in this experiment is a 6-helix barrel. Moreover, the special properties of the film of Polyetheretherketone (PEEK) material are used to cover the surface of the barrel helix with a virtual in-mold decoration (IMD) film, and the unique nature of the film die offset in the IMD is utilized to detect the position of the barrel helix. The area with a large die index is the area with a large helix offset in the barrel, and the IMD die index is introduced to quantify the data. The IMD die index is used to determine the helix offset of the damaged barrel. The novelty of this work is that each node can use the die index to efficiently detect the position of the barrel helix deviation, carry out subsequent optimization and repair work through the optimization of the injection molding parameters and the design optimization of the barrel and verify the experiment by comparing the results. Through the steady-state simulation research mode, different permutations and combinations of the two process parameters are simulated to study their effects. Quantitative reference indicators include but are not limited to dependent variables such as the fluid flow velocity, shear rate, temperature distribution and phase transition, and the shear heating process of the injection screw is taken into account in the mold flow analysis to ensure that the die index value is more accurate. It can be seen from the analysis results that the temperature of the barrel changes after the groove depth and groove width are changed, and the effect ratio of the groove depth is lower than that of the groove width in the same degree of size change.

Abstract Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.