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The purpose of this study was to examine the dietary views and practices and to identify associated barriers to and facilitators of healthy eating of rural residents emerging from poverty in the context of rapid socio-economic development. A qualitative design with semi-structured interviews was utilized to collect detailed insights into the dietary behaviors of 22 rural residents from 10 villages in Fengshan town, Dafang county, Guizhou province, China. Thematic analysis was applied to interpret the interview data, guided by the socio-ecological model. Four themes were identified: traditional eating patterns, factors influencing food choice, limited knowledge of healthy diet, and lack of nutritional guidance. Barriers to healthy eating included traditional but unhealthy foods, limited nutritional knowledge, inadequate understanding of nutritional requirements, overwhelming nutritional information, and limited professional guidance. Facilitators encompassed healthy traditional eating patterns, household composition, home gardening, preference for traditional bean and soy products, improved food supply and availability owing to poverty alleviation efforts, and being open to receiving professional dietary guidance. As a preliminary investigation into the dietary views and practices of this population, the study highlights a significant gap in the nutritional knowledge and guidance available to rural residents in China, emphasizing the need for comprehensive strategies that address the complex socio-ecological factors influencing dietary behaviors.

Steamed green tea has a long history and unique aroma, but little is known about its key aroma components. In this study, 173 volatiles in steamed green tea were identified using solvent-assisted flavor evaporation and headspace-solid phase microextraction plus two chromatographic columns of different polarities. Aroma extract dilution analysis revealed 48 highly aroma-active compounds with flavor dilution factors 64-1024. Internal standards were used to calculate odorant active value (OAV), and 11 OAV > 1 key aroma compounds were determined. Omission test identified eight substances, including dimethyl sulfide, (E)-β-ionone, cis-jasmone, linalool, nonanal, heptanal, isovaleraldehyde and (Z)-3-hexenol, as the key aroma active compounds of steamed green tea. With the increase of withering degree, the content of these substances increased first and then decreased except for heptanal and cis-jasmone. Moreover, the water content of 62 % was suggested to be an appropriate withering degree during the processing of steamed green tea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study used samples processed with an innovative manufacturing process to explore the dynamic changes of large-leaf yellow tea (LYT) in color, aroma, and taste substances, and the quality components were most significantly affected in the stages of first pile-yellowing (FP) and over-fired drying (TD). In this process, the moisture and temperature conditions caused chlorophyll degradation, Maillard reactions, caramelization reactions, and isomerization of phenolic substances, forming the quality of LYT. Specifically, chlorophyll degradation favored the formation of color quality; the taste quality was determined by the content of soluble sugars, amino acids, catechins, etc.; the aroma quality was dependent on the content changes of alcohols and aldehydes, as well as the increase of sweet and roasting aroma substances in the third drying stage. Additionally, twelve key aroma components, including linalool, (E)-β-ionone, 2,3-diethyl-5-methyl-pyrazine, etc., were identified as contributors to revealing LYT rice crust-like and sweet aroma formation mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In the past few years, a burgeoning interest has emerged in applying gamification to promote desired health behaviors. However, little is known about the effectiveness of such applications in the HIV prevention and care continuum among men who have sex with men (MSM)., Objective: This study aims to summarize and evaluate research on the effectiveness of gamification on the HIV prevention and care continuum, including HIV-testing promotion; condomless anal sex (CAS) reduction; and uptake of and adherence to pre-exposure prophylaxis (PrEP), postexposure prophylaxis (PEP), and antiretroviral therapy (ART)., Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and the Journal of Medical Internet Research and its sister journals for studies published in English and Chinese from inception to January 2024. Eligible studies were included when they used gamified interventions with an active or inactive control group and assessed at least one of the following outcomes: HIV testing; CAS; and uptake of and adherence to PrEP, PEP, and ART. During the meta-analysis, a random-effects model was applied. Two reviewers independently assessed the quality and risk of bias of each included study., Results: The systematic review identified 26 studies, including 10 randomized controlled trials (RCTs). The results indicated that gamified digital interventions had been applied to various HIV outcomes, such as HIV testing, CAS, PrEP uptake and adherence, PEP uptake, and ART adherence. Most of the studies were conducted in the United States (n=19, 73%). The most frequently used game component was gaining points, followed by challenges. The meta-analysis showed gamification interventions could reduce the number of CAS acts at the 3-month follow-up (n=2 RCTs; incidence rate ratio 0.62, 95% CI 0.44-0.88). The meta-analysis also suggested an effective but nonstatistically significant effect of PrEP adherence at the 3-month follow-up (n=3 RCTs; risk ratio 1.16, 95% CI 0.96-1.38) and 6-month follow-up (n=4 RCTs; risk ratio 1.28, 95% CI 0.89-1.84). Only 1 pilot RCT was designed to evaluate the effectiveness of a gamified app in promoting HIV testing and PrEP uptake. No RCT was conducted to evaluate the effect of the gamified digital intervention on PEP uptake and adherence, and ART initiation among MSM., Conclusions: Our findings suggest the short-term effect of gamified digital interventions on lowering the number of CAS acts in MSM. Further well-powered studies are still needed to evaluate the effect of the gamified digital intervention on HIV testing, PrEP uptake, PEP initiation and adherence, and ART initiation in MSM., (© Qianqian Luo, Yue Zhang, Wei Wang, Tianyu Cui, Tianying Li. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite., Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue., Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated., Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Li et al.)

Photosensitive supercapacitors incorporate light-sensitive materials on capacitive electrodes, enabling solar energy conversion and storage in one device. In this study, heterogeneous structures of rod-shaped ZnO decorated with Ce 2 S 3 nanoparticles on nickel foam (ZnO@Ce 2 S 3 /NF) are synthesized using a two-step hydrothermal method as photosensitive supercapacitor electrodes for capacitance enhancement under visible light. The formation of ZnO@Ce 2 S 3 heterogeneous structures is confirmed using various structural characterization techniques. The area-specific capacitance of the ZnO@Ce 2 S 3 /NF composite electrode increased from 1738.1 to 1844.0 mF cm -2 after illumination under a current density of 5 mA cm -2 , which is 2.4 and 2.8 times higher than that of ZnO and Ce 2 S 3 electrodes under similar conditions, respectively, indicating the remarkable light-induced capacitance enhancement performance. The ZnO@Ce 2 S 3 /NF electrode also exhibits a higher photocurrent and photovoltage than the two single electrodes, demonstrating its excellent photosensitivity. The improved capacitance performance and photosensitivity under illumination are attributed to the well-constructed energy-level structure, which stimulates the flow of photogenerated electrons from the outer circuit and the involvement of photogenerated holes in the resulting surface-controlled capacitance. In addition, the assembled ZnO@Ce 2 S 3 /NF-based hybrid supercapacitor exhibits a great energy density of 145.0 mWh cm -2 under illumination. This study provides a novel strategy for the development of high-performance solar energy conversion/storage devices., (© 2023 Wiley‐VCH GmbH.)

Objective: To explore the influence of serum metabolites on the risk of psoriasis., Methods: In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages., Results: In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism., Conclusion: Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Zheng, Lv, Tang, Zhong, Luo, Bi, Yang, Zhong, Chen and Lu.)

Aim: This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH)., Methods: Using varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single-cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post-ICH were profiled using single-cell RNA sequencing (scRNA-seq). Gene Ontology (GO) and gene set variation analysis (GSVA) further interpreted the differentially expressed genes (DEGs)., Results: Following WMH induction, there was a notable increase in the percentage of myeloid cells and oligodendrocyte precursor cells (OPCs), alongside a reduction in the percentage of neurons, microglia, and oligodendrocytes (OLGs). Post-ICH WMH showed homeostatic microglia transitioning into pro-, anti-inflammatory, and proliferative states, influencing lipid metabolic pathways. Myeloid cells amplified chemokine expression, linked with ferroptosis pathways. Macrophages exhibited M1 and M2 phenotypes, and post-WMH, macrophages displayed a predominance of M2 phenotypes, characterized by their anti-inflammatory properties. A surge in OPC proliferation aligned with enhanced ribosomal signaling, suggesting potential reparative responses post-WMH., Conclusion: The study offers valuable insights into WMH's complex pathophysiology following ICH, highlighting the significance and utility of scRNA-seq in understanding the cellular dynamics and contributing to future cerebrovascular research., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood. Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models. Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement. Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP's modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Zheng, Luo, Li, Yang, Bi, Chen, Han, Chen and Lu.)

Fungicides are commonly applied through root irrigation in tobacco fields to control soil-borne diseases, and they affect soil microorganisms. However, the effects of metalaxyl-M and hymexazol, used to manage tobacco black shank disease, on these soil microecology remain poorly understood. This study employed high-throughput sequencing technology to explore the soil physical and chemical properties, soil enzyme activity, and the diversity, community structure and function of soil fungi in tobacco fields following root irrigation with metalaxyl-M and hymexazol. The results revealed that ammonium nitrogen (NH 4 + -N), nitrate nitrogen (NO 3 - -N), soil organic matter (SOM), electrical conductivity (EC) and soil urease (UE) in soil were significantly increased and the pH decreased after root-irrigation with these two fungicides. The abundance of soil fungal community was significantly reduced after the root-irrigation of metalaxyl-M and hymexazol. The relative abundance of Ascomycota increased significantly after the treatment with metalaxyl-M. Following hymexazol treatment, the abundance of Achroiostachys, Nigrospora, Ustilaginoidea, and Trichoderma significantly decreased. Functional prediction analysis indicated an increase in the relative abundance of functional genes of saprophytic fungi after treatment with both fungicides. This study provides a foundational understanding of the environmental behavior and supports the scientific and rational use of metalaxyl-M and hymexazol in soil.

Background: Psoriasis is an immune-mediated chronic inflammatory skin disease. Great progress has been made in the pathogenesis of psoriasis in recent years, but there is no bibliometric study on the pathogenesis of psoriasis. The purpose of this study was to use bibliometrics method to analyze the research overview and hot spots of pathogenesis of psoriasis in recent 10 years, so as to further understand the development trend and frontier of this field., Methods: The core literatures on the pathogenesis of psoriasis were searched in the Web of Science database, and analyzed by VOSviewer, CiteSpace, and Bibliometrix in terms of the annual publication volume, country, institution, author, journal, keywords, and so on., Results: A total of 3570 literatures were included. China and the United States were the main research countries in this field, and Rockefeller University was the main research institution. Krueger JG, the author, had the highest number of publications and the greatest influence, and Boehncke (2015) was the most cited local literature. J INVEST DERMATOL takes the top spot in terms of the number of Dermatol articles and citation frequency. The main research hotspots in the pathogenesis of psoriasis are as follows: (1) The interaction between innate and adaptive immunity and the related inflammatory loop dominated by Th17 cells and IL-23/IL-17 axis are still the key mechanisms of psoriasis; (2) molecular genetic studies represented by Long Non-Coding RNA (LncRNA); (3) integrated research of multi-omics techniques represented by gut microbiota; and (4) Exploring the comorbidity mechanism of psoriasis represented by Metabolic Syndrome (MetS)., Conclusion: This study is a summary of the current research status and hot trend of the pathogenesis of psoriasis, which will provide some reference for the scholars studying the pathogenesis of psoriasis., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Cancer cachexia is a systemic inflammation-driven syndrome, characterized by muscle atrophy and adipose tissue wasting, with progressive weight loss leading to serious impairment of physiological function. Extracellular vesicles (EVs) derived from cancer cells play a significant role in adipocyte lipolysis, yet the mechanism remain uneclucidated. In this study, EVs derived from Lewis lung carcinoma (LLC) cells were extracted and characterized. 3T3-L1 and HIB1B adipocytes were cultured with conditioned medium or EVs from LLC, and LLC cells were used to establish a cancer cachexia mouse model. EVs derived from LLC cells were taken up by 3T3-L1 and HIB1B adipocytes, and derived exosomal EIF5A protein-induced lipolysis of adipocytes. High level of EIF5A was expressed in EVs from LLC cells, exosomal EIF5A is linked to lipid metabolism. Elevated expression of EIF5A is associated with shorter overall survival in lung cancer patients. Western blots, glycerol release and Oil red O staining assays were used to evaluate lipolysis of adipocytes. The reduction of lipolysis in 3T3-L1 and HIB1B adipocytes is achieved through silencing EIF5A or treating with pharmacologic inhibitor GC7 in vitro, and suppressing the expression of EIF5A in LLC cells by infected with shRNA or GC7 treatment partly alleviated white and brown adipose tissue lipolysis in vivo. Mechanistically, EIF5A directly binds with G protein-coupled bile acid receptor 1 (GPBAR1) mRNA to promote its translation and then activates cAMP response element binding protein (CREB) signaling pathway to induce lipolysis. This study demonstrates that exosomal EIF5A from LLC cells, with hypusinated EIF5A, has a lipolytic effect on adipocyte and adipose tissues in cancer cachexia model. Exosomal EIF5A could be involved in lipolysis and these findings indicate that a novel regulator and potential target for cachexia treatment., Competing Interests: Declaration of Competing Interest The author declare that they have no competing interest that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypobaric hypoxia (HH) exposure affects appetite and serum iron levels in both humans and animals. Thus, whether appetite-regulating ghrelin is involved in iron regulation under HH needs to be elucidated. In vivo, C57BL/6J mice were placed in a hypobaric chamber to establish a 6000-m-high altitude exposure animal model. In vitro, mouse primary hepatocytes and peritoneal macrophages were exposed to hypoxia (1% O 2 ) to examine the effects of ghrelin on iron-regulating proteins. HH obviously reduced the body weight of mice and significantly increased the levels of erythrocytes, and also significantly enhanced the levels of serum iron and plasma ghrelin. However, iron content in the liver and spleen was decreased, while ferroportin (Fpn) expression was increased. Moreover, ghrelin significantly induced Fpn and pERK expression in both hepatocytes and macrophages under hypoxia, which were reversed by pretreatment with growth hormone secretagogue receptor 1a (GHSR1a) antagonist or pERK inhibitor. Our findings indicated that HH leads to decreased appetite and insufficient dietary intake, which may negatively regulate the levels of ghrelin. Furthermore, GHSR1a/ERK signalling pathway is further activated to upregulate the expression of Fpn, and then promoting iron mobilization both in the liver/hepatocytes and spleen/macrophages in mice. Thus, these results revealed that ghrelin may be a potential iron regulatory hormone, and raised the possibility of ghrelin as a promising therapeutic target against iron disorders under HH., (© 2023. The Author(s).)

Fermentation is the key technology for black tea aroma formation. The key aroma substances of black tea at different fermentation stages (unfermented (WDY), underfermented (F1H), fully fermented (F4H), and overfermented (F8H)) were characterized by the methodology of Sensomics. Aroma extract dilution analysis was performed on volatile fractions extracted by using solvent-assisted flavor evaporation and solid-phase microextraction, yielding 93 odor-active areas. Internal standard method plus stable isotope dilution analysis was used for quantitative analysis. The omission experiment identified 23 aroma substances. Further reduction and addition experiments revealed phenylacetaldehyde, ( E , E )-2,4-heptadienal, geraniol, linalool, β-damascenone, 2-methylbutyraldehyde, dimethyl sulfide, and isovaleraldehyde with odor activity values (OAV) > 100 as the characteristic aroma components of F4H and also as the main contributors to aroma differences between different fermentation degrees. The green odor of ( E , E )-2,4-heptadienal was highlighted in WDY and F1H relative to that in F4H due to the lower contribution of phenylacetaldehyde and β- damascenone in the former two samples. Additionally, excessive OAV increase of fatty aldehydes in F8H masked its similar floral and fruity aroma.

Objective: Exploring the predictive power of frailty combined with nutritional risk on postoperative complications in elderly gastrointestinal malignancies patients., Methods: Elderly patients who underwent gastrointestinal cancer surgery at Gastrointestinal Surgery Department of the Affiliated Hospital of Binzhou Medical University from August 2021 to June 2022 were selected as the research subjects. The patients' frailty and nutritional status were assessed using the Fried Frailty Scale and the NRS2002 Nutritional Risk Scale within 24 h of admission. Observing and recording the diagnosis and treatment of postoperative complications during the hospitalization., Results: 202 patients were enrolled, including 119 patients (58.91%) with nutritional risk and 89 patients (44.06%) with frailty. Frailty was an independent risk factor for postoperative complications [OR = 5.904, 95%CI (3.103, 11.233)]. The AUC value of frailty assessment was 0.780, which was greater than the AUC value of NRS2002 score of 0.705 (P < 0.01). The AUC value of frailty assessment combined with NRS-2002 score was 0.844, which was significantly higher than that alone (P < 0.01)., Conclusions: The ability of frailty to predict postoperative complications is better than the NRS-2002 score. Frailty combined with nutritional risk assessment can increase the predictive power of postoperative complications in elderly gastrointestinal malignancies patients., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Patients with type 2 diabetes Mellitus (T2DM) are more likely to suffer from a higher uric acid level in blood-hyperuricemia (HUA). There are no conclusive studies done to predict HUA among T2DM patients. Therefore, this study aims to explore the risk factors of HUA among T2DM patients and finally suggest a model to help with its prediction., Method: In this retrospective research, all the date were collected between March 2017 and October 2019 in the Medical Laboratory Center of the First Affiliated Hospital of Xinjiang Medical University. The information included sociodemographic factors, blood routine index, thyroid function indicators and serum biochemical markers. The least absolute shrinkage and selection operator (LASSO) and multivariate binary logistic regression were performed to screen the risk factors of HUA among T2DM patients in blood tests, and the nomogram was used to perform and visualise the predictive model. The receiver operator characteristic (ROC) curve, internal validation, and clinical decision curve analysis (DCA) were applied to evaluate the prediction performance of the model., Results: We total collected the clinical date of 841 T2DM patients, whose age vary from 19-86. In this study, the overall prevalence of HUA in T2DM patients was 12.6%. According to the result of LASSO-logistic regression analysis, sex, ethnicity, serum albumin (ALB), serum cystatin C (CysC), serum inorganic phosphorus (IPHOS), alkaline phosphatase (ALP), serum bicarbonate (CO2) and high-density lipoprotein (HDLC) were included in the HUA risk prediction model. The nomogram confirmed that the prediction model fits well (χ 2  = 5.4952, P = 0.704) and the calibration curve indicates the model had a good calibration. ROC analysis indicates that the predictive model shows the best discrimination ability (AUC = 0.827; 95% CI: 0.78-0.874) whose specificity is 0.885, and sensitivity is 0.602., Conclusion: Our study reveals that there were 8 variables that can be considered as independent risk factors for HUA among T2DM patients. In light of our findings, a predictive model was developed and clinical advice was given on its use., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Men who have sex with men (MSM) in China hold a low-risk perception of acquiring HIV. This has resulted in an inadequate HIV testing rate., Objective: This study aims to investigate whether administering HIV risk self-assessments with tailored feedback on a gay geosocial networking (GSN) app could improve HIV testing rates and reduce sexual risk behaviors in Chinese MSM., Methods: We recruited MSM from Beijing, China, who used the GSN platform Blued in October 2017 in this 12-month double-blinded randomized controlled trial. From October 2017 to September 2018, eligible participants were randomly assigned to use a self-reported HIV risk assessment tool that provided tailored feedback according to transmission risk (group 1), access to the same HIV risk assessment without feedback (group 2), or government-recommended HIV education materials (control). All interventions were remotely delivered through the mobile phone-based app Blued, and participants were followed up at 1, 3, 6, and 12 months from baseline. The number of HIV tests over the 12-month study was the primary outcome and was assessed using an intention-to-treat analysis with an incident rate ratio (IRR). Unprotected anal intercourse (UAI) over 6 months was assessed by a modified intention-to-treat analysis and was the secondary outcome. All statistical analyses were conducted in SAS 9.3 (SAS Institute, Inc.), and a P value <.05 was considered statistically significant., Results: In total, 9280 MSM were recruited from baseline and were randomly assigned to group 1 (n=3028), group 2 (n=3065), or controls (n=3187). After follow-up, 1034 (34.1%), 993 (32.4%), and 1103 (34.6%) remained in each group, respectively. Over 12 months, group 1 took 391 tests (mean of 2.51 tests per person), group 2 took 352 tests (mean of 2.01 tests per person), and controls took 295 tests (mean of 1.72 tests per person). Group 1 had significantly more HIV testing than the control group (IRR 1.32, 95% CI 1.09-4.58; P=.01), while group 2 did not differ significantly from the controls (IRR 1.06, 95% CI 0.86-1.30; P=.60). The proportion of UAI was not statistically different among different groups, but all 3 groups had UAI, which declined from baseline., Conclusions: Repeated HIV risk assessments coupled with tailored feedback through GSN apps improved HIV testing. Such interventions should be considered a simple way of improving HIV testing among MSM in China and increasing awareness of HIV status., Trial Registration: ClinicalTrials.gov NCT03320239; https://clinicaltrials.gov/study/NCT03320239., (©Qianqian Luo, Zunyou Wu, Guodong Mi, Jie Xu, Sarah Robbins Scott. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.09.2023.)

Effective ways to identify and predict men who have sex with men (MSM) at substantial risk for HIV is a global priority. HIV risk assessment tools can improve individual risk awareness and subsequent health-seeking actions. We sought to identify and characterize the performance of HIV infection risk prediction models in MSM through systematic review and meta-analysis. PubMed, Embase, and The Cochrane Library were searched. Eighteen HIV infection risk assessment models with a total of 151,422 participants and 3643 HIV cases were identified, eight of which have been externally validated by at least one study (HIRI-MSM, Menza Score, SDET Score, Li Model, DHRS, Amsterdam Score, SexPro model, and UMRSS). The number of predictor variables in each model ranged from three to 12, age, the number of male sexual partners, unprotected receptive anal intercourse, recreational drug usage (amphetamines, poppers), and sexually transmitted infections were critical scoring variables. All eight externally validated models performed well in terms of discrimination, with the pooled area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95%CI: 0.51 to 0.73, SDET Score) to 0.83 (95%CI: 0.48 to 0.99, Amsterdam Score). Calibration performance was only reported in 10 studies (35.7%, 10/28). The HIV infection risk prediction models showed moderate-to-good discrimination performance. Validation of prediction models across different geographic and ethnic environments is needed to ensure their real-world application., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Hypoxia-induced neuronal damage is the primary cause of cognitive impairment induced by high-altitude exposure. Microglia play a crucial regulatory role in the central nervous system (CNS) homeostasis and synaptic plasticity. M1-type polarized microglia are suspected to be responsible for CNS injury under hypoxic conditions, but the exact molecular mechanism is still unelucidated., Methods: CX3CR1 knock out and wide type mice were exposed to a simulated plateau at 7000 m for 48 h to construct the model of hypobaric hypoxia-induced memory impairment. The memory impairment of mice was assessed by Morris water maze. The dendritic spine density in the hippocampus was examined by Golgi staining. The synapses in the CA1 region and the number of neurons in the DG region were examined by immunofluorescence staining. The synapses in microglia activation and phagocytosis were examined by immunofluorescence. The levels of CX3CL1/CX3CR1 and their downstream proteins were detected. CX3CR1 knockout primary microglia were treated with CX3CL1 combined with 1% O 2 . The levels of proteins related to microglial polarization, the uptake of synaptosome and phagocytotic ability of microglia were detected., Results: In this study, mice exposed to a simulated 7000 m altitude for 48 h developed significant amnesia for recent memories, but no significant change in their anxiety levels was observed. Hypobaric hypoxia exposure (7000 m altitude above sea level for 48 h) resulted in synapse loss in the CA1 region of the hippocampus, but no significant changes occurred in the total number of neurons. Meanwhile, microglia activation, increased phagocytosis of synapses by microglia, and CX3CL1/CX3CR1 signal activation were observed under hypobaric hypoxic exposure. Further, we found that after hypobaric hypoxia exposure, CX3CR1-deficient mice showed less amnesia, less synaptic loss in the CA1 region, and less increase in M1 microglia, compared to their wildtype siblings. CX3CR1-deficient microglia did not exhibit M1-type polarization in response to either hypoxia or CX3CL1 induction. Both hypoxia and CX3CL1 induced the phagocytosis of synapses by microglia through the upregulation of microglial phagocytosis., Discussion: The current study demonstrates that CX3CL1/CX3CR1 signal mediates the M1-type polarization of microglia under high-altitude exposure and upregulates microglial phagocytosis, which increases the phagocytosis of synapses in the CA1 region of the hippocampus, causing synaptic loss and inducing forgetting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xie, Niu, Wan, Lu, Luo and Zhu.)

Background: Human umbilical cord mesenchymal stem cells (hUCMSCs, retrospectively registered) have a lot of promise for treating theca interstitial cells(TICs) dysfunction in premature ovarian insufficiency (POI). The mechanisms, however, are still unknown., Methods: To examine the therapeutic and find the cause, we used both in vivo cisplatin-induced POI rat model and in vitro TICs model. HUCMSCs were injected into the tail veins of POI rats in an in vivo investigation. Then, using ELISA, HE staining, TUNEL apoptosis test kit, immunohistochemistry and western blot, researchers examined hormonal levels, ovarian morphology, TICs apoptosis, NR4A1 and Cyp17a1 in response to cisplatin treatment and hUCMSCs. TICs were obtained from the ovaries of rats and treated with the cisplatin, hUCMSCs supernatant, and the antagonist of NR4A1--DIM-C-pPhOH. ELISA, immunofluorescence, flow cytometry, JC-1 labeling and western blot analysis were used to detect T levels, Cyp17a1, NR4A1, and the anti-apoptotic protein Bcl-2, as well as pro-apoptotic proteins Bax, caspase-9, caspase-3, and cytochrome C(cytc)., Results: We discovered that hUCMSCs restored the ovarian function, particularly TICs function based on measures of Cyp17a1 and T expression. NR4A1 was found in ovarian TICs of each group and NR4A1 expression was lower in the POI rats but higher following hUCMSCs therapy. The apoptosis of TICs generated by cisplatin was reduced after treatment with hUCMSCs. In vitro, NR4A1 was expressed in the nucleus of TICs, and NR4A1 as well as phospho-NR4A1 were decreased, following the apoptosis of TICs was emerged after cisplatin treatment. Interestingly, the localization of NR4A1 was translocated from the nucleus to the cytoplasm due to cisplatin. HUCMSCs were able to boost NR4A1 and phospho-NR4A1 expression while TICs' apoptosis and JC-1 polymorimonomor fluorescence ratios reduced. Furthermore, Bcl-2 expression dropped following cisplatin treatment, whereas Bax, cytc, caspase-9, and caspase-3 expression rose; however, hUCMSCs treatment reduced their expression. In addition, DIM-C-pPhOH had no effect on the NR4A1 expression, but it did increase the expression of apoptosis-related factors such as Bax, cytc, caspase-9, and caspase-3, causing the apoptosis of TICs., Conclusions: These data show that hUCMSCs therapy improves ovarian function in POI rats by inhibiting TICs apoptosis through regulating NR4A1 -mediated mitochondrial mechanisms., (© 2022. The Author(s).)

Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. In vivo results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis.

Long chain non-encoding RNA (lncRNA) can affect gene expression through transcription, post transcriptional regulation and epigenetic modification, and it is involved in regulating ovarian physiological function. LncRNA, as a competitive endogenous RNA, can affect the expression of target gene mRNA by competitively binding microRNA (miRNA), which are called lncRNA/miRNA/mRNA regulatory network. It plays an important role in the regulation of ovarian physiological function and the occurrence and development of ovarian reproductive disorders, expecting to become a new target and diagnostic index for the treatment of reproductive disorders.

The liver is contributed to maintaining body iron homeostasis and controlling of body adaptation to fasting. Although previous studies implied a negative relationship between iron and ghrelin in both mice and humans, it remains to be explored whether fasting or ghrelin has a functional effect on iron homeostasis in the liver. In this study, we examined the roles of fasting and ghrelin in modulating the protein expression of Fpn1, transferrin receptor 1 (TfR1), and ferritin light chain (Ft-L), as well as the mRNA expression of ghrelin, hepcidin, ghrelin O-acyltransferase (GOAT), and growth hormone secretagogue receptor 1 alpha (GHSR1α) in mouse liver and cultured hepatocytes. Our in vivo results suggested that fasting significantly upregulated the mRNA expression of ghrelin, GOAT, and GHSR1α, as well as the protein levels of ghrelin, Fpn1, and Ft-L, but not TfR1, in mouse liver. Interestingly, mRNA expression of hepcidin did not change significantly after fasting. Meanwhile, in cultured hepatocytes, ghrelin significantly increased the protein expression of Fpn1 but not Ft-L and TfR1 and significantly enhanced ERK phosphorylation. Furthermore, the pretreatment of cultured hepatocytes with either a pERK inhibitor or a GHSR1α antagonist abolished the effects of ghrelin on Fpn1 expression and ERK phosphorylation. Our findings confirmed that fasting increases iron export in the liver by upregulating Fpn1 expression through the ghrelin/GHSR1α/MAPK signaling pathway.

Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant molecular mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathological changes were assessed for up to 28 days post-injury with or without VPA treatment. Primary OPCs were harvested and used to study the effect of VPA on OPC differentiation under inflammatory conditions. VPA dose-dependently attenuated learning and memory deficits and robustly protected white matter after FDL induction, as demonstrated by reductions in SMI-32 and increases in myelin basic protein staining. VPA also promoted OPC proliferation and differentiation and increased subsequent remyelination efficiency by day 28 post-FDL induction. VPA treatment did not affect HDAC1, HDAC2 or HDAC8 expression but reduced HDAC3 protein levels. In vitro, VPA improved the survival of mouse OPCs and promoted their differentiation into oligodendrocytes following lipopolysaccharide (LPS) stimulation. LPS caused OPCs to overexpress HDAC3, which translocated from the cytoplasm into the nucleus, where it directly interacted with the nuclear transcription factor PPAR-γ and negatively regulated PPAR-γ expression. VPA decreased the expression of HDAC3 and promoted remyelination and functional neurological recovery after FDL. These findings may support the use of strategies modulating HDAC3-mediated regulation of protein acetylation for the treatment of demyelination-related cognitive dysfunction.

Objective: The basic pathological changes of primary ovarian insufficiency (POI) include ovarian tissue fibrosis and follicular development disorders. The human umbilical cord mesenchymal stem cell (hUMSC) transplantation has been shown an effective method to improve the ovarian function in POI rat model; however, the exact mechanisms are still unclear. The purpose of this study is to investigate whether the recovery of ovarian function in POI rats is related to the inhibition of tissue fibrosis following hUMSC transplantation. Furthermore, the transforming growth factor-β 1 (TGF-β 1 ) signaling pathway is explored to determine the mechanisms of ovarian function recovery through its inhibition of tissue fibrosis., Methods: The primary ovarian insufficiency (POI) rat model was established by intraperitoneal injection of chemotherapy drug cisplatin (CDDP) for 7 days. The levels of serum sex hormones were measured using enzyme-linked immunosorbent assay (ELISA). The tissue fibrosis in the ovary was examined using Masson staining and Sirius red staining. The collagen fibers in the ovarian tissues were detected by Western blot analysis. To investigate the mechanisms of ovarian function recovery following hUMSC transplantation, ovarian stromal cells were isolated from the ovarian cortex of immature rats. The expression of Cytochrome P450 17A1 (Cyp17a1) and fibrosis marker of alpha smooth muscle actin (α-SMA) in ovarian stromal cells was examined using immunofluorescence analysis. Also, the protein levels of Cyp17a1 and α-SMA in ovarian stromal cells were examined by Western blot analysis. The expression of TGF-β 1 and Smad3 signals was measured by Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis., Results: The results show that the function of the ovary in POI rats was significantly improved after hUMSC transplantation. The expression of fibrosis markers (α-SMA) and production of Collagen Type I (Collagen I) and Collagen Type III (Collagen III) in POI rats were significantly inhibited in POI rats following hUMSC transplantation. In the cultured ovarian stromal cells, the decrease of TGF-β 1 and p-Smad3 protein expression was observed in hUMSC-treated POI rats. The treatment with TGF-β 1 inhibitor of SB431542 further confirmed this signal pathway was involved in the process., Conclusion: Our study demonstrated that the TGF-β 1 /Smad3 signaling pathway was involved in the inhibition of ovarian tissue fibrosis, which contributed to the restoration of ovarian function in POI rats following hUMSC transplantation.

Human placenta mesenchymal stem cells (hPMSCs), have been extensively investigated on the treatment of many diseases. This study was to explore the effects of hPMSCs treatment on the chemotherapy drug-induced premature ovarian insufficiency (POI) mice. Cyclophosphamide (120 mg/kg) and busulfan (30 mg/kg) or cyclophosphamide (70 mg/kg) induced POI mice were used and hPMSCs were injected through tail vein. The hormone levels of serum, morphological changes, the expression and quantitative analysis of inhibin B (INHBB) and FSHR protein, and apoptosis of granulosa cells in ovary were detected. The granulosa cells (GCs) were detected from ovaries of mice and the different concentration of cyclophosphamide on GCs were detected by MTT assay. The apoptosis of GCs was detected by FITC Annexin V Apoptosis Detection Kit. The significant increase in FSH and decrease in E 2 and INHBB were observed. Expression of human nuclei was observed in the stroma of ovaries. INHBB and FSHR levels of ovaries were reduced in the POI mice. Following hPMSCs treatment, the amounts of INHBB and FSHR significantly increased close to normal levels. The granulosa cells apoptosis increased in the POI ovaries but decreased after hPMSCs treatment. Moreover, cyclophosphamide has no effect on the GCs and no statistic difference was measured in vitro. The effects of hPMSCs treatment reduce the apoptosis of granulosa cells and restore the ovarian reserve capacity in chemotherapeutic drug-induced POI mice. The data help to further explore new potential clinical therapeutic approach for POI patients.

Background: Cleistanthin A (CleA), a natural diphyllin glycoside, has been shown to suppress the invasion of cancer cells, but the underlying mechanisms remain unclear. Here, the inhibitory effect of CleA on the invasion of MDA-MB-231 human breast cancer cells was investigated, and the mechanisms involved were clarified., Methods: Cell viability was studied by MTT assay. The migration and invasion of MDA-MB-231 cells were assessed by wound healing assay and transwell assay, respectively. The enzymatic activity of matrix metalloproteinases (MMPs) was detected by gelatin zymography. mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. Nuclear translocation of β-catenin was observed by immunofluorescence and detected by Western blotting., Results: CleA effectively inhibited the migration and invasion of MDA-MB-231 cells and suppressed the expression and activation of MMP-2/9. Moreover, the expression and nuclear translocation of β-catenin were reduced by CleA treatment, as well as transcription of the Cyclin D1 and c-myc genes. In addition, the inhibitory effect of CleA on the β-catenin pathway was attributed to the promotion of β-catenin degradation by inhibition of GSK3β phosphorylation. When the phosphorylation of GSK3β was induced by LiCl, the inhibitory effect of CleA on the β-catenin pathway and the invasion of MDA-MB-231 cells were almost reversed., Conclusion: CleA suppressed the invasion of MDA-MB-231 cells, likely through the β-catenin pathway.

A human immunodeficiency virus (HIV) risk assessment tool was previously developed for predicting HIV infection among men who have sex with men (MSM), but was not externally validated. We evaluated the tool's validity for predicting HIV infection in an independent cohort.The tool was assessed using data from a retrospective cohort study of HIV-negative adult MSM who were recruited in Beijing, China between January 2009 and December 2016.High-risk behaviors occurring within 6 months before the survey were evaluated. Area under curve (AUC) of the receiver operating character curve (ROC) was used to quantify discrimination performance; calibration curve and Hosmer-Lemeshow statistic were used for calibration performance valuation; and decision curve analysis (DCA) was used to evaluate clinical usage.One thousand four hundred forty two participants from the cohort were included in the analysis; 246 (17.1%) sero-converted during follow-up. External validation of the tool showed good calibration, the Hosmer-Lemeshow test showed no statistical difference between observed probability and tool-based predictive probability of HIV infection (X = 4.55, P = .80). The tool had modest discrimination ability (AUC = 0.63, 95% confidence interval [CI]: 0.61-0.66). The decision curve analysis indicated that implementing treatment measures based on the tool's predicative risk thresholds ranging from 10% to 30% might increase the net benefit of treatment when compared with treating all or no MSM.The HIV risk assessment tool can predict the actual risk of HIV infection well amongst MSM in China, but it has a moderate ability to discriminate those at high risk of HIV infection.

Background: Demyelination is the end product of numerous pathological processes, and also is one of the main causes of neurological disability in Multiple sclerosis (MS). Research into the pathogenesis of MS is hampered by the conventional rodent models' inability to produce stable demyelination., New Method: Focal demyelinating lesions were stereotactically targeted to the corpus callosum with a two-point injection of lysophosphatidylcholine (LPC-2) in mice. Three groups were analyzed (n = 8, each) and water maze, sensorimotor test, and compound action potential were included in functional tests. Electron microscopy was used for morphological analyses while western blot and immunohistochemistry were included for molecular detection., Results: Ten days after the LPC-2 injection, the expression of myelin basic protein (MBP) was reduced, while non-phosphorylated neurofilament (SMI-32) was increased. The amplitude of the N1 segment decreased and less well-defined myelin sheaths was found. Behavioral tests showed increased latency to escape and reduced time spent in target quadrant. Four weeks later, MBP expression still reduced, SMI-32 expression was increased, both spatial learning (D24-D27) and spatial memory (D28) were still significantly impaired in LPC-2 injection mice., Comparison With Existing Method(s): Compared with the classic single-point LPC-injection model, our studies showed that the two-point LPC-injection not only could induce demyelination in a short-term manner, but also could cause demyelination in a long-term manner with little remyelination in the mouse corpus callosum., Conclusions: We established a simple, reliable, and inexpensive model of demyelination in the corpus callosum in mice, with functional and morphological reproducibility, and good validity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation., Methods: The inhibitor of PI3K/Akt was administered to observe its effect on ovarian function recovery and immune regulation. Serum levels of estradiol (E 2 ), follicle stimulation hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were measured by ELISA to evaluate ovarian function. The morphological changes of ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was determined by detecting the expression of capase-3. Expression of p-Akt protein was detected by immunohistochemistry and western blot assay in ovarian tissues. The MTT assay was performed to assess GC proliferation. GC apoptosis was performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was measured by ELISA., Results: LY294002 administration decreased serum levels of E 2 and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared with mice in the hPMSC transplantation group. The ovarian morphology presented as atrophy and fibrosis, with functional follicles exhausted. The expression of p-Akt in ovarian tissue was significantly decreased. Also, LY294002 administration significantly decreased proliferation and increased cell apoptosis in GCs, and for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly increased, as well as the serum levels of IL-17., Conclusions: Our data suggest that the PI3K/Akt signal pathway is involved in the recovery of ovarian function by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following hPMSC transplantation.

Objective: To explore the mechanism of chemotherapy drug induced ovarian injury in premature ovarian failure (POF) mice., Methods: C57BL/6 mice were treated with Cyclophosphamide and Busulfan by intraperitoneal injection. One week after treatment, the estrous cycles, folliculogenesis, ovarian endocrine function and ovarian histopathological changes were evaluated the ovarian function. The serum levels of cytokines, follicle stimulating hormone (FSH) and estradiol (E 2 ) were measured by enzyme-linked immunosorbent assay (ELISA). The protein levels of SDF-1/CXCR4 and FSHR in ovary were evaluated by immunohistochemistry and Western blot analysis. The ovarian cells apoptosis was measured by TUNEL Assay., Results: The ovaries from POF mice show the evidence of reduced ovarian function such as irregular estrous cycles, stromal hyperplasia, decreased follicle numbers, atresia follicles and less granular cell layer as well as corpora luteum. The lower levels of E 2 and higher levels of FSH in serum characterize the ovarian injury; a great number of granular apoptotic cells were observed in the POF mice; the serum concentrations of pro-inflammatory cytokines of IL-6, IL-8 and TNF-α level were increased but anti-inflammatory cytokine of IL-10 was decreased. SDF-1/CXCR4 and FSHR expressed in ovaries were detected in the cytoplasm of preantral and antral follicles; the expression of SDF-1/CXCR4 was increased and FSHR was decreased in POF mice., Conclusion: Our data suggest that the inflammatory regulation, SDF-1/CXCR4 and cellular apoptosis in ovarian tissues are involved in the development of ovarian injury of POF. These data provide useful information to develop new therapeutic approach to treat POF disorders in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Reproductive endocrine disorder induced by negative energy balance is very common in recent years. But underlying mechanism of reproductive disorders still remains elusive. It is reported that leptin/leptinR-kisspeptin/kiss1r system plays a critical role in reproductive field. Therefore, this study was to determine the role of leptin/leptinR in the expression of kisspeptin/kiss1r during negative energy balance and effect of leptin/leptinR-kisspeptin/kiss1r on puberty onset., Materials and Methods: Wistar female rats aged 28days were divided into four groups. The saline and leptin treatment groups were treated through intracerebroventricular injection while 72h-fasting. Body weight and serum hormone levels were recorded. The levels of mRNA and protein of kisspeptin, kiss1r, GnRH and leptinR were measured by QT-PCR, Immunofluorescence and Western blot, respectively., Key Findings: Kisspeptin, kiss1r and GnRH expression was detected in the cytoplasm but leptinR in the nucleus. After fasting, the results show a significant decrease in body weight, serum levels of leptin, LH and FSH concentrations and the expression of kisspeptin/kiss1r, GnRH mRNA and reproductive endocrine peptides. Leptin administration had no effects on body weight but it was found that the serum levels of leptin, LH and FSH were increased. Leptin shows slight effects on inhibiting the suppression of fasting. The leptinR expression of ARC increased after fasting and was restricted by leptin injection., Significance: Leptin/leptinR-kisspeptin/kiss1r-GnRH pathway is responsible for the regulation of neuroendocrine hormones due to its effect on the protein or mRNA expression. Subsequently, it affects the reproductive function, especially could delay puberty onset., (Copyright © 2016 Elsevier Inc. All rights reserved.)