Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice. / Nrf2ä»‹å¯¼çš„ç”Ÿç²¾ç»†èƒžé“æ­»äº¡å‚ä¸Žäº†èšè‹¯ä¹™çƒ¯çº³ç±³å¡‘æ–™å¯¼è‡´çš„å°é¼ é›„æ€§ç”Ÿæ®–æ¯’æ€§.

Microplastics (MPs) and nanoplastics (NPs) have become hazardous materials due to the massive amount of plastic waste and disposable masks, but their specific health effects remain uncertain. In this study, fluorescence-labeled polystyrene NPs (PS-NPs) were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo. Interestingly, whole-body imaging found that PS-NPs accumulated in the testes of mice. Therefore, the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice, and their mechanisms, were investigated. After oral exposure to PS-NPs, their spermatogenesis was affected and the spermatogenic cells were damaged. The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing (RNA-seq) to determine the toxic mechanisms; a ferroptosis pathway was found after PS-NP exposure. The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1 (Fer-1), and it was also found that nuclear factor erythroid 2-related factor 2 (Nrf2) played an important role in spermatogenic cell ferroptosis induced by PS-NPs. Finally, it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity. This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

A novel perspective on di-hexyl phthalate (2-ethylhexyl)-induced reproductive toxicity in females: Lipopolysaccharide synergizes with mono-2-ethylhexyl ester to cause inflammatory apoptosis rather than autophagy in ovarian granulosa cells.

Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian granulosa cells (GCs), but the interrelationships between DEHP's on autophagy, apoptosis, and inflammation in GCs are not clear. Our previous study demonstrated that DEHP exposure resulted in the disturbance of intestinal flora associated with serum LPS release, which in turn led to impaired ovarian function. LPS has also been shown to determine cell fate by modulating cellular autophagy, apoptosis, and inflammation. Therefore, this study investigated the role and link between LPS and autophagy, apoptosis, and inflammation of GCs in DEHP-induced ovarian injury. Here, we constructed an in vivo injury model by continuous gavage of 0-1500 mg/kg of DEHP in female mice for 30 days and an in vitro injury model by treatment of human ovarian granulosa cells (KGN) cells with mono-2- ethylhexyl ester (MEHP, an active metabolite of DEHP in vivo). In addition, the expression of relevant pathway molecules was detected by immunohistochemistry, immunofluorescence, qRT-PCR, and Western blotting after the addition of the autophagy inhibitor 3-methyladenine (3-MA), the apoptosis inhibitor Z-VAD- FMK and the NF-κB inhibitor BAY11-7082. The current study found that autophagy and apoptosis were significantly activated in GCs of DEHP-induced atretic follicles in vivo and found that MEHP-induced KGN cells autophagy and apoptosis were independent and potentially cytotoxic of each other in vitro. Further studies confirmed that DEHP exposure resulted in LPS release from the intestinal tract and entering the ovary, thereby participating in DEHP-induced inflammation of GCs. In addition, we found that exogenous LPS synergized with MEHP could activate the NF-κB signaling pathway to induce inflammation and apoptosis of GCs in a relatively prolonged exposure condition. Meanwhile, inhibition of inflammatory activation could rescue apoptosis and estrogen secretion function of GCs induced by MEHP combined with LPS. These results indicated that the increased LPS influenced by DEHP might cooperate with MEHP to induce inflammatory apoptosis of GCs, an important cause of ovarian injury in mice.

Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.

BACKGROUND: As the population ages, mild cognitive impairment (MCI) and type 2 diabetes mellitus (T2DM) become common conditions that often coexist. Evidence has shown that MCI could lead to reduced treatment compliance, medication management, and self-care ability in T2DM patients. Therefore, early identification of those with increased risk of MCI is crucial from a preventive perspective. Given the growing utilization of decision trees in prediction of health-related outcomes, this study aimed to identify MCI in T2DM patients using the decision tree approach. METHODS: This hospital-based case-control study was performed in the Endocrinology Department of Xiangya Hospital affiliated to Central South University between March 2021 and December 2022. MCI was defined based on the Petersen criteria. Demographic characteristics, lifestyle factors, and T2DM-related information were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was established using the chi-square automatic interaction detection (CHAID) algorithm to identify key predictor variables associated with MCI. The area under the curve (AUC) value was used to evaluate the performance of the established decision tree model, and the performance of multivariate regression model was also evaluated for comparison. RESULTS: A total of 1001 participants (705 in the training set and 296 in the validation set) were included in this study. The mean age of participants in the training and validation sets was 60.2  ±  10.3 and 60.4  ±  9.5 years, respectively. There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI, including age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy. The established decision tree model had 15 nodes composed of 4 layers, and age is the most significant predictor variable. It performed well (AUC = .75 [95% confidence interval (CI): .71-.78] and .67 [95% CI: .61-.74] in the training and validation sets, respectively), was internally validated, and had comparable predictive value compared to the multivariate logistic regression model (AUC = .76 [95% CI: .72-.80] and .69 [95% CI: .62-.75] in the training and validation sets, respectively). CONCLUSION: The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate logistic regression model and was internally validated. Due to its superior classification accuracy and simple presentation as well as interpretation of collected data, the decision tree model is more recommended for the prediction of MCI in T2DM patients in clinical practice.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Sleep quality and its associated factors among patients with type 2 diabetes mellitus in Hunan, China: a cross-sectional study.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a serious public health issue. Compared with the general population, patients with T2DM have a higher risk of poor sleep quality, which could ultimately result in poor prognosis. Therefore, this study aimed to evaluate sleep quality and its associated factors among patients with T2DM in Hunan, China. DESIGN: This was a cross-sectional study. SETTING: A tertiary hospital in Hunan, China. PARTICIPANTS: Patients with T2DM hospitalised at the Endocrinology Department were consecutively enrolled between March 2021 and December 2022. Sociodemographic characteristics, lifestyle factors and T2DM-related information were collected retrospectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, with a cut-off value of >7 suggesting poor sleep quality. Multivariate logistic regression analysis was used to determine factors associated with poor sleep quality. RESULTS: Of the 1039 participants included, 1001 provided complete data. The mean age of the study sample was 60.24±10.09 years, and 40.5% (95% CI 37.5% to 43.5%) of patients had poor sleep quality. Multivariate logistic regression analysis showed that female sex (adjusted OR (aOR) 1.70, 95% CI 1.25 to 2.29), unmarried status (aOR 1.72, 95% CI 1.05 to 2.83), diabetic retinopathy (aOR 1.38, 95% CI 1.04 to 1.83), diabetic foot (aOR 1.80, 95% CI 1.11 to 2.93) and a per capita monthly household income of >5000 RMB (aOR 0.66, 95% CI 0.47 to 0.93) were associated with poor sleep quality. CONCLUSIONS: Nearly two-fifths of patients with T2DM reported poor sleep quality in Hunan, China. Sex, marital status, diabetic retinopathy, diabetic foot and household income were independently associated with sleep quality among patients with T2DM in Hunan, China.

Metabolomic analysis of plasma biomarkers in children with autism spectrum disorders.

Autism spectrum disorder (ASD) presents a significant risk to human well-being and has emerged as a worldwide public health concern. Twenty-eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9-O-18:0), DL-2-hydroxystearic acid, and 7(S),17(S)-dihydroxy-8(E),10(Z),13(Z),15(E),19(Z)-docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three-biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.

The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition.

Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.

Facile synthesis of dual-ligand europium-metal organic gels for ratiometric electrochemiluminescence detecting I27L gene.

Metal organic gels (MOGs) are a new kind of intelligent soft materials with excellent luminescence properties. However, MOGs with dual electrochemiluminescence (ECL) properties have not been reported. In this study, using Eu3+ as metal node, 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine (Hcptpy) and Luminol as organic ligands, a novel dual-ligand Europium-organic gels (Eu-L-H MOGs) were prepared by simple mixing at room temperature. On the one hand, Eu-L-H MOGs could exhibit strong and stable anodic ECL signals in the phosphate buffered saline (PBS) without the addition of co-reactants, which came from the blue emission of Luminol. On the other hand, using K2S2O8 as a cathodic co-reactant, Eu-L-H MOGs produced cathodic signals, which were derived from the red emission of Eu sensitized by Hcptpy through the antenna effect. Based on the independent dual ECL signals of Eu-L-H MOGs, we selected Alexa Flour 430 as the receptor and anodic ECL emission of Eu-L-H MOGs as the donor to construct the ECL resonance energy transfer (ECL-RET) ratio biosensor, which utilized exonuclease III assisted DNA cycle amplification to achieve ultrasensitive detection of the I27L gene. The detection linearity of I27L ranged from 1 fM to 10 nM, with a detection limit as low as 284 aM. This study developed a straightforward technique for obtaining a single luminescent material with dual signals, and further broadened the analytical application of MOGs in the realm of ECL.

Relationship between dietary macronutrients intake and biological aging: a cross-sectional analysis of NHANES data.

PURPOSE: This study aimed to investigate the association between macronutrient intake and biological age. METHODS: Data were collected from 26,381 adults who participated in the United States National Health and Nutrition Examination Survey (NHANES). Two biological ages were estimated using the Klemera-Doubal method (KDM) and PhenoAge algorithms. Biological age acceleration (AA) was computed as the difference between biological age and chronological age. The associations between macronutrient intakes and AA were investigated. RESULTS: After fully adjusting for confounding factors, negative associations were observed between AA and fiber intake (KDM-AA: ß - 0.53, 95% CI - 0.62, - 0.43, P < 0.05; PhenoAge acceleration: ß - 0.30, 95% CI - 0.35, - 0.25, P < 0.05). High-quality carbohydrate intake was associated with decreased AA (KDM-AA: ß - 0.57, 95% CI - 0.67, - 0.47, P < 0.05; PhenoAge acceleration: ß - 0.32, 95% CI - 0.37, - 0.26, P < 0.05), while low-quality carbohydrate was associated with increased AA (KDM-AA: ß 0.30, 95% CI 0.21, 0.38, P < 0.05; PhenoAge acceleration: ß 0.16, 95% CI 0.11, 0.21, P < 0.05). Plant protein was associated with decreased AA (KDM-AA: ß - 0.39, 95% CI - 0.51, - 0.27, P < 0.05; PhenoAge acceleration: ß - 0.21, 95% CI - 0.26, - 0.15, P < 0.05). Long-chain SFA intake increased AA (KDM-AA: ß 0.16, 95% CI 0.08, 0.24, P < 0.05; PhenoAge acceleration: ß 0.11, 95% CI 0.07, 0.15, P < 0.05). ω-3 PUFA was associated with decreased KDM-AA (ß - 0.18, 95% CI - 0.27, - 0.08, P < 0.05) and PhenoAge acceleration (ß - 0.09, 95% CI - 0.13, - 0.04, P < 0.05). CONCLUSION: Our findings suggest that dietary fiber, high-quality carbohydrate, plant protein, and ω-3 PUFA intake may have a protective effect against AA, while low-quality carbohydrate and long-chain SFA intake may increase AA. Therefore, dietary interventions aimed at modifying macronutrient intakes may be useful in preventing or delaying age-related disease and improving overall health.

Ratiometric Electrochemiluminescence of Zirconium Metal-Organic Framework as a Single Luminophore for Sensitive Detection of HPV-16 DNA.

This study developed a new zirconium metal-organic framework (MOF) luminophore named Zr-DPA@TCPP with dual-emission electrochemiluminescence (ECL) characteristics at a resolved potential. First, Zr-DPA@TCPP with a core-shell structure was effectively synthesized through the self-assembly of 9,10-di(p-carboxyphenyl)anthracene (DPA) and 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) as the respective organic ligands and the Zr cluster as the metal node. The reasonable integration of the two organic ligands DPA and TCPP with ECL properties into a single monomer, Zr-DPA@TCPP, successfully exhibited synchronous anodic and cathodic ECL signals. Besides, due to the impressively unique property of ferrocene (Fc), which can quench the anodic ECL but cannot affect the cathodic ECL signal, the ratiometric ECL biosensor was cleverly designed by using the cathode signal as an internal reference. Thus, combined with DNA recycle amplification reactions, the ECL biosensor realized sensitive ratiometric detection of HPV-16 DNA with the linear range of 1 fM-100 pM and the limit of detection (LOD) of 596 aM. The distinctive dual-emission properties of Zr-DPA@TCPP provided a new idea for the development of ECL luminophores and opened up an innovative avenue of fabricating the ratiometric ECL platform.

Nannies Go Rogue? A Call for Research into Nanny-Induced Elderly Abuse in China.

Older people often face varied and vicious abuse from care workers. Situations are often more pronounced for older people who live with additional cognitive or physical difficulties, such as dementia and disabilities, the prevalence of which has been on the rise in China and elsewhere. Recent discoveries of elderly abuse in China, which span from alarming levels of verbal, physical, psychological, financial, to sexual abuse, are all caused by nannies or "bao mu". Different from Western countries, the word nanny is often used to refer to people who offer caregiving help in residential settings at large, regardless of the age of the care recipients. What is also different is the lack of regulations or even rigorous training and evaluation processes for nannies in China: almost anyone could become a nanny-even though a background check is often required for nannies, this process is often highly variable and dependent on the specific labour agencies that nannies are registered with. Yet without structured studies and systematic data, little is known about the extent and severity of nanny-induced elderly abuse in China. To this end, this paper aims to discuss the unique elderly care environment-such as the "721 Rule"-in China, particularly in the post-COVID era, and highlight the critical need for timely and rigorous studies on the potential prevalence and severity of nannies' abuse and neglect of older people.

TMEM147 aggravates the progression of HCC by modulating cholesterol homeostasis, suppressing ferroptosis, and promoting the M2 polarization of tumor-associated macrophages.

BACKGROUND: The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms. METHODS: TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of TMEM147 on the progression of HCC. Proteins interacting with TMEM147 were identified via RNA-seq, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to determine and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Extensive experimental techniques were used to study ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using immunofluorescence assay and flow cytometric analysis. RESULTS: TMEM147 mRNA and protein levels were increased in HCC cells, and the increased TMEM147 expression was associated with a poor survival. TMEM147 promoted tumor cell proliferation and metastases in vitro and in vivo. The protein was found to interact with the key enzyme 7-dehydrocholesterol reductase (DHCR7), which affected cellular cholesterol homeostasis and increased the extracellular levels of 27HC in HCC cells. TMEM147 also promoted the expression of DHCR7 by enhancing the activity of signal transducer and activator of transcription 2. 27HC expression upregulated glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC expression increased the lipid metabolism in macrophages and activated peroxisome proliferator-activated receptor-γ signaling, thereby activating M2 macrophage polarization and promoting HCC cell invasion and migration. CONCLUSIONS: Our results indicate that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. These findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC.

Inhibition of α2,6-sialyltransferase relieves symptoms of ulcerative colitis by regulating Th17 cells polarization.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease that affects human intestines. Immune imbalance is one of the important factors inducing UC. After the activation of CD4+ T cells, pro-inflammatory cytokines are produced to induce colonic inflammation. α2,6-Sialylation, catalyzed by α2,6-sialyltransferase (ST6GAL1), affects the proliferation, activation, and T cell receptor (TCR) signaling of CD4+ T cells, but its role in CD4+ T cell polarization, regulation of Th17 / Treg balance, and its role in UC are still unclear. We found the number of CD4+ T and Th17 cells increased in colonic tissue with UC. The level of α2,6-sialylation of CD4+ T cells in patients with UC was significantly increased. De-α2,6-sialylation significantly reduced the symptoms of UC in rats. ST6GAL1 gene knockout inhibited the polarization of CD4+ T cells to Th17 cells, and promoted the polarization of CD4+ T cells to Treg cells. ST6GAL1 knockout significantly inhibited the IL-17 signaling pathway in CD4+ T cells and inhibited the secretion of pro-inflammatory cytokine IL-17a. ST6GAL1 and IL-17a are highly expressed in patients with UC, and there is a positive correlation between them. In conclusion, reduced α2,6-sialylation inhibits the polarization of CD4+ T cells to Th17 cells, inhibits IL-17a signaling pathway and reduces the level of pro-inflammatory cytokine IL-17a to alleviate the symptoms of UC, which is a potential novel target for the clinical treatment of UC.

Development and validation of frailty and malnutrition knowledge assessment scale for community-dwelling older adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population, two scales were developed and validated through five phases. Phase 1: the item pools were constructed through a literature review and research panel based on the symptom interpretation model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales each comprise 3 dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all >0.60, Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 min. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) alleviate excessive autophagy of ovarian granular cells through VEGFA/PI3K/AKT/mTOR pathway in premature ovarian failure rat model.

BACKGROUND: Premature ovarian failure (POF) is one of the leading causes of female infertility and is accompanied by abnormal endocrine, seriously affecting female quality of life. Previous studies have demonstrated that mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for POF. However, the mechanism remains obscure. This study aims to investigate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on ovarian function in the POF rat model and explore the underlying mechanisms. METHODS: The ovarian function was evaluated by ovarian morphology, histology, estrous cycle, hormone levels (AMH, E2, FSH, and LH), and fertility ability to investigate the effect of hUC-MSCs on the POF rats model. The cytokines levels were assayed in serum using protein array to explore the mechanisms of hUC-MSCs therapy for POF. The excessive autophagy levels were evaluated using a co-culture system of 3D MSCs spheroids with human ovarian granulosa cell line (KGN) or primary ovarian granulosa cells (GCs) to understand the paracrine effect of hUC-MSCs on GCs. The related proteins expression of autophagy and PI3K/AKT/mTOR pathway was detected using Western Blotting and/or in various inhibitors supplement to further demonstrate that vascular endothelial growth factor A (VEGFA) secreted by hUC-MSCs can alleviate excessive autophagy of ovarian GCs via PI3K/AKT/mTOR signaling pathway. The ovarian culture model in vitro was applied to confirm the mechanism. RESULTS: The ovarian function of POF and the excessive autophagy of ovarian GCs were restored after hUC-MSCs transplantation. The protein array result demonstrated that VEGF and PI3K/AKT might improve ovarian function. in vitro experiments demonstrated that VEGFA secreted by hUC-MSCs could decrease oxidative stress and inhibit excessive autophagy of ovarian GCs via PI3K/AKT/mTOR pathway. The ovarian culture model results confirmed this mechanism in vitro. CONCLUSION: The hUC-MSCs can alleviate excessive autophagy of ovarian GCs via paracrine VEGFA and regulate the PI3K/AKT/mTOR signaling pathway, thereby improving the ovarian function of POF.

Activation of the p62-Keap1-Nrf2 pathway protects against oxidative stress and excessive autophagy in ovarian granulosa cells to attenuate DEHP-induced ovarian impairment in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.

Prevalence of Anxiety and Associated Factors Among Inpatients with Type 2 Diabetes Mellitus in China: A Cross-Sectional Study.

This study aimed to investigate the prevalence of anxiety and its associated factors among inpatients with type 2 diabetes mellitus (T2DM) in China. This study was a cross-sectional study. Inpatients with T2DM admitted to the Endocrinology Department of Xiangya Hospital, Central South University in Hunan Province of China from March 2021 to December 2021 were consecutively included in this study. Participants were interviewed to obtain the data on socio-demographic characteristics, lifestyle characteristics, T2DM-related information, and social support. Anxiety was measured using the Hospital Anxiety and Depression Scale-anxiety subscale by experienced physicians. Multivariable logistic regression analysis was used to estimate the independent contribution of each independent variable to anxiety. A total of 496 inpatients with T2DM were included in this study. The prevalence of anxiety was 21.8% (95% confidence interval [CI]: 18.1%-25.4%). The results of multivariable logistic regression analysis indicated that age of at least 60 (adjusted odd ratio [aOR] = 1.79, 95% CI: 1.04-3.08), and having diabetes specific complications (aOR = 4.78, 95% CI: 1.02-22.44) were risk factors for anxiety, and an educational level of high school or above (aOR = 0.55, 95% CI: 0.31-0.99), regular physical activity (aOR = 0.36, 95% CI: 0.22-0.58), and high social support (aOR = 0.30, 95% CI: 0.17-0.53) were protective factors for anxiety. A predictive model based on these five variables showed good performance (area under the curve = 0.80). Almost one in five inpatients with T2DM suffered from anxiety in China. Age, educational level, regular physical activity, diabetes specific complications, and social support were independently associated with anxiety.

High-Efficiency Aluminum-Metal Organic Framework/HEPES Electrochemiluminescence System for Ultrasensitive Detection of HBV DNA.

In this work, a novel aluminum metal-organic framework (Al-MOF)/N-2-hydroxyethylpiperazine-N'-ethane-sulfonic acid (HEPES) system with an excellent electrochemiluminescence (ECL) property was developed. First, Al-MOF was successfully synthesized through a one-pot solvothermal method by using 9,10-di(p-carboxyphenyl)anthracene (DPA) as the organic luminescence ligand and Al3+ as the metal node. Compared with DPA, Al-MOF showed high ECL intensity and excellent stability without an additional coreactant in the HEPES buffer. The corresponding ECL mechanism was studied in detail, verifying HEPES was not only the buffer in the system but also the coreactant of Al-MOF. In particular, the system of Al-MOF/HEPES showed a high ECL efficiency of 30.0%, taking the Ru(bpy)32+ system as the standard. In addition, the ECL signal of Al-MOF was effectively quenched by dopamine (DA). The biosensor for HBV DNA detection was constructed through the ECL signal on-off-on mode of DNA specific recognition integrated with the DNA walker signal amplification strategy. The ultrasensitive detection for HBV DNA was achieved with a linear range of 100 aM to 10 pM and a limit of detection (LOD) of 62.1 aM. This work proposed a high-efficiency Al-MOF/HEPES system, providing a new viewpoint for a coreactant-free system in the field of ECL.

The use of nomogram for detecting mild cognitive impairment in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram-based model to detect mild cognitive impairment (MCI) in T2DM patients. METHODS: Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well-qualified investigators conducted face-to-face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM-related information, and history of depression and anxiety. Cognitive function was assessed using the Mini-Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively. RESULTS: A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%-38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815-0.883), and the threshold probability ranged from 35.0% to 85.0%. CONCLUSIONS: Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.

Prevalence of comorbid depression and associated factors among hospitalized patients with type 2 diabetes mellitus in Hunan, China.

BACKGROUND: Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China. METHODS: This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants' data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1. RESULTS: The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3-31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02-3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30-0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11-0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615. CONCLUSIONS: Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.