Highly Pathogenic Avian Influenza A Virus in Wild Migratory Birds, Qinghai Lake, China, 2022.

In July 2022, an outbreak of highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b occurred among migratory birds at Qinghai Lake in China. The virus circulated in June, and reassortants emerged after its introduction into the area. Surveillance in 2023 showed that the virus did not establish a stable presence in wild waterfowl.

Effect of Immune Thrombocytopenic Purpura Medications on Depression Risk: An Analysis of NHANES Data.

BACKGROUND: Immune thrombocytopenic purpura (ITP) in adults typically develops slowly and insidiously. The ITP medications might be linked to psychological disorders, but the connection is not well-understood. OBJECTIVE: This study aimed to examine the association between ITP medication use and the risk of depression among participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. METHODS: Using data from 70 190 NHANES participants, we conducted a cross-sectional study, excluding individuals under 18 years, with hypertension, HIV, hepatitis C, and various comorbidities. A total of 17 299 individuals were included in the analysis of this study. We identified 2 populations within this study: those using ITP medications, including prednisone, dexamethasone, and rituximab and those not using ITP drugs. Depression status was assessed using the Patient Health Questionnaire-9 (PHQ-9), and the relationship between ITP medication use and depression was analyzed through multivariate logistic regression. RESULTS: There was no significant association between ITP medication use and an increased risk of depression after adjusting for demographic and health-related variables. Notably, among the study participants, 1.8% of the non-depressed population were on ITP medication compared with 0.3% in the depressed population. The analysis revealed varying depression risks associated with different sociodemographic factors. For instance, the correlation between ITP medication and depression risk was influenced by a combination of age, race, income, and smoking status. CONCLUSION AND RELEVANCE: The study suggests that ITP medication use does not independently increase the risk of depression. This finding is crucial for guiding clinical decisions and managing patient expectations regarding ITP treatment and its psychological impacts.

Associations between antenatal depressive symptoms in different trimesters and perinatal outcomes: A prospective multicenter cohort study in China.

BACKGROUND: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester. METHODS: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses. RESULTS: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted ß=0.026, 95 % CI: 0.003-0.050). CONCLUSION: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester.

Engineered mouse H1 promoter mutants with superior RNA polymerase III activity.

Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter. Furthermore, to boost its Pol III activity, we engineered various promoter mutants by introducing mutations or systematically swapping elements. Surprisingly, the Pol II activity of mH1 core mut5 with AT stretch was at least 2-fold greater than that of the wild type, making it a potential candidate for target protein expression purposes. Fortunately, the Pol III activities of mH1 mut1 and mH1 core mut5 were at least 1.5 times stronger than those of the parental promoters in human and mouse cell lines on account of AT stretch, as did the mH1 mut4 with AT stretch and proximal sequence element (PSE) and TATA box insertion mutations. We highly recommend these three promoters as valuable supplements to the type 3 Pol III promoter toolbox.

Molecular Control of the Donor/Acceptor Interface Suppresses Charge Recombination Enabling High-Efficiency Single-Component Organic Solar Cells.

Single-component organic solar cells based on double cable polymers have achieved remarkable performance, with DCPY2 reaching a high efficiency of over 13%. In this study, DCPY2 is further optimized with an efficiency of 13.85%, maintaining a high fill factor (FF) without compromising the short circuit current. Despite its intermixed morphology, DCPY2 shows a reduced recombination rate compared to their binary counterpart (PBDB-T:Y-O6). This slower recombination in DCPY2 is attributed to the reduced wavefunction overlap of delocalized charges, achieved by spatially separating the donor and acceptor units with an alkyl linker, thereby restricting the recombination pathways. Adding 1,8-diiodooctane (DIO) into DCPY2 further reduced the recombination rate by facilitating acceptor aggregation, allowing free charges to become more delocalized. The DIO-assisted aggregation in DCPY2 (5% DIO) is evidenced by an increased pseudo-pure domain size of Y-O6. Fine molecular control at the donor/acceptor interface in the double-cable polymer achieves reduced non-geminate recombination under efficient charge generation, increased mobility, and charge carrier lifetime, thereby achieving superior performance. Nevertheless, the FF is still limited by relatively low mobility compared to the blend, suggesting the potential for further mobility improvement through enhanced higher-dimensional packing of the double-cable material.

Microplasma-assisted construction of cross-linked network hierarchical structure of NiMoO4 nanorods @NiCo-LDH nanosheets for electrochemical sensing of non-enzymatic H2O2 in food.

The accumulation of small doses of hydrogen peroxide (H2O2) into food can cause many diseases in the human body, and it is urgent to develop efficient detection methods of H2O2. Herein, the hierarchical structure composite of NiCo-LDH nanosheets crosslinked NiMoO4 nanorods was grown in situ on carbon cloth (NiMoO4 NRs@NiCo-LDH NSs/CC) by micro-plasma assisted hydrothermal method. Thanks to the synergistic effect of three metals and (NiMoO4 NRs@NiCo-LDH NSs/CC) provided by nanorods/nanosheets hierarchical structure, NiMoO4 NRs@NiCo-LDH NSs/CC exposes more active sites and achieves rapid electron transfer. The H2O2 electrochemical sensor was constructed as the working electrode with a linear range of 1 µmol L-1 to 9.0 mmol L-1 and detection limit of 112 nmol L-1. In addition, the sensor has been successfully applied to the detection of H2O2 in food samples, the recovery rate is 95.2%-106.62%, RSD < 4.89%.

Parkinson's image detection and classification based on deep learning.

OBJECTIVE: There are two major issues in the MRI image diagnosis task for Parkinson's disease. Firstly, there are slight differences in MRI images between healthy individuals and Parkinson's patients, and the medical field has not yet established precise lesion localization standards, which poses a huge challenge for the effective prediction of Parkinson's disease through MRI images. Secondly, the early diagnosis of Parkinson's disease traditionally relies on the subjective judgment of doctors, which leads to insufficient accuracy and consistency. This article proposes an improved YOLOv5 detection algorithm based on deep learning for predicting and classifying Parkinson's images. METHODS: This article improves the YOLOv5s network as the basic framework. Firstly, the CA attention mechanism was introduced to enable the model to dynamically adjust attention based on local features of the image, significantly enhancing the sensitivity of the model to PD related small pathological features; Secondly, replace the dynamic full dimensional convolution module to optimize the multi-level extraction of image features; Finally, the coupling head strategy is adopted to improve the execution efficiency of classification and localization tasks separately. RESULTS: We validated the effectiveness of the proposed method using a dataset of 582 MRI images from 108 patients. The results show that the proposed method achieves 0.961, 0.974, and 0.986 in Precision, Recall, and mAP, respectively, and the experimental results are superior to other algorithms. CONSLUSION: The improved model has achieved high accuracy and detection accuracy, and can accurately detect and recognize complex Parkinson's MRI images. SIGNIFICANCE: This algorithm has shown good performance in the early diagnosis of Parkinson's disease and can provide clinical assistance for doctors in early diagnosis. It compensates for the limitations of traditional methods.

Design, synthesis and biological activity evaluation of eco-friendly rosin-based fungicides for sustainable crop protection.

BACKGROUND: Utilizing fungicides to protect crops from diseases is an effective method, and novel eco-friendly plant-derived fungicides with high efficiency and low toxicity are urgent requirements for sustainable crop protection. RESULT: Two series of rosin-based fungicides (totally 35) were designed and synthesized. In vitro fungicidal activity revealed that Compound 6a (Co. 6a) effectively inhibited the growth of Valsa mali [median effective concentration (EC50) = 0.627 µg mL-1], and in vivo fungicidal activity suggested a significant protective efficacy of Co. 6a in protecting both apple branches (35.12% to 75.20%) and apples (75.86% to 90.82%). Quantum chemical calculations (via density functional theory) results indicated that the primary active site of Co. 6a lies in its amide structure. Mycelial morphology and physiology were investigated to elucidate the mode-of-action of Co. 6a, and suggested that Co. 6a produced significant cell membrane damage, accelerated electrolyte leakage, decreased succinate dehydrogenase (SDH) protein activity, and impaired physiological and biochemical functions, culminating in mycelial mortality. Molecular docking analysis revealed a robust binding energy (ΔE = -7.29 kcal mol-1) between Co. 6a and SDH. Subsequently, biosafety evaluations confirmed the environmentally-friendly nature of Co. 6a via the zebrafish model, yet toxicological results indicated that Co. 6a at median lethal concentration [LC50(96)] damaged the gills, liver and intestines of zebrafish. CONCLUSION: The above research offers a theoretical foundation for exploiting eco-friendly rosin-based fungicidal candidates in sustainable crop protection. © 2024 Society of Chemical Industry.

High-Detectivity All-Polymer Photodiode Empowers Smart Vitality Surveillance and Computational Imaging Rivaling Silicon Diodes.

Near-infrared (NIR) organic photodetectors (OPDs), particularly all-polymer-based ones, hold substantial commercial promise in the healthcare and imaging sectors. However, the process of optimizing their active layer composition to achieve highly competitive figures of merit lacks a clear direction and methodology. In this work, celebrity polymer acceptor PY-IT into a more NIR absorbing host system PBDB-T:PZF-V, to significantly enhance the photodetection competence, is introduced. The refined all-polymer ternary broadband photodetector demonstrates superior performance metrics, including experimentally measured noise current as low as 6 fA Hz-1/2, specific detectivity reaching 8 × 1012 Jones, linear dynamic range (LDR) of 145 dB, and swift response speed surpassing 200 kHz, striking a fair balance between sensitivity and response speed. Comprehensive morphological and photophysical characterizations elucidate the mechanisms behind the observed performance enhancements in this study, which include reduced trap density, enhanced charge transport, diminished charge recombination, and balanced electron/hole mobilities. Moreover, the practical deployment potential of the proof-of-concept device in self-powered mode is demonstrated through their application in a machine learning-based cuffless blood pressure (BP) estimation system and in high-resolution computational imaging across complex environments, where they are found to quantitatively rival commercial silicon diodes.

Associations between maternal early pregnancy depression and longitudinal fetal growth.

BACKGROUND: The impacts of maternal depression during mid-to-late pregnancy on fetal growth have been extensively investigated. However, the association between maternal depression during early pregnancy and fetal intrauterine growth are less clear. METHODS: A prospective study comprised 23,465 eligible pregnant women and their offspring was conducted at a hospital-based center in Shanghai. Prenatal depression was assessed used using Patient Health Questionnaire (PHQ-9) before 14 gestational weeks. Differences in fetal growth trajectory of different maternal depressive statuses during three periods (16-23, 24-31, and 32-41 gestational weeks) were compared using a multilevel model with fractional polynomials. RESULTS: Women with depressive symptoms during early pregnancy had higher longitudinal fetal trajectories, with an estimated increase in fetal weight (ß = 0.33; 95 % CI, 0.06-0.61), compared to those without depressive symptoms. Increases in fetal abdominal circumference among women with depressive symptoms were observed before 23 gestational weeks. Offspring born to mothers with early pregnancy depression had a significantly higher birth weight of 14.13 g (95 % CI, 1.33-27.81 g) and an increased risk of severe large size for gestational age (adjusted odds ratio [aOR], 1.64; 95 % CI, 1.32-2.04) and macrosomia (aOR, 1.21; 95 % CI, 1.02-1.43). LIMITATIONS: Self-rated scale was used to assess depressive symptoms rather than clinical diagnosis. And Long-term effects of early pregnancy depression on offspring were not explored. CONCLUSIONS: The study revealed an association between maternal depression during early pregnancy and increased fetal biometrics, higher birth weight, and an elevated risk of severe large size for gestational age and macrosomia.

Insulator Polymer Matrix Construction on All-Small-Molecule Photoactive Blend Towards Extrapolated 15000 Hour T80 Stable Devices.

To boost the stability of all-small-molecule (ASM) organic photovoltaic (OPV) blends, an insulator polymer called styrene-ethylene-butylene-styrene (SEBS) as morphology stabilizer is applied into the host system of small molecules BM-ClEH:BO-4Cl. Minor addition of SEBS (1 mg/ml in host solution) provides a significantly enhanced T80 value of 15000 hours (extrapolated), surpassing doping-free (0 mg/ml) and heavy doping (10 mg/ml) counterparts (900 hours, 30 hours). The material reproducibility and cost-effectiveness of the active layer will not be affected by this industrially available polymer, where the power conversion efficiency (PCE) can be well maintained at 15.02%, which is still a decent value for non-halogen solvent-treated ASM OPV. Morphological and photophysical characterizations clearly demonstrate SEBS's pivotal effect on suppressing the degradation of donor molecules and blend film's crystallization/aggregation reorganization, which protects the exciton dynamics effectively. This work pays meaningful attention to the ASM system stability, performs a smart strategy to suppress the film morphology degradation, and releases a comprehensive understanding of the mechanism of device performance reduction.

A gel plaster in the form of nipple cover: A comfortable and safe transdermal delivery method for mammary hyperplasia.

Hyperplasia of mammary glands (HMG) is considered a precancerous condition with a risk of malignant transformation, highlighting the necessity of proactive treatment in the early stages. Transdermal drug delivery offers significant advantages such as painlessness, absence of first-pass effect, and good patient compliance. However, the unique structure of the breast requires transdermal formulations for treating mammary hyperplasia to exhibit higher levels of safety and comfort. We have formulated an ancient topical formula called 'Muxiang Bing,' comprising traditional Chinese medicines Aucklandiae Radix (AR) and Rehmanniae Radix (RR), for the treatment of HMG. This formula has been transformed into a gel paster in the form of nipple cover for trans-nipple-areola delivery. In our investigations, we observed that the optimal formulation of the Muxiang gel plaster demonstrated enhanced permeation facilitated by AR's effect on RR. Furthermore, pre-treatment with the Muxiang gel plaster improved mammary tissue morphology, hormone levels, oxidative stress, aberrant cell proliferation, and damage in rat models, thus preventing and ameliorating mammary hyperplasia. The Muxiang gel plaster exhibited low skin irritability in rats, and long-term use did not cause harm to their internal organs or blood cells, indicating its safety and efficacy.

A Prototype of Graphene E-Nose for Exhaled Breath Detection and Label-Free Diagnosis of Helicobacter Pylori Infection.

Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis.

Updates of primary central nervous system lymphoma.

Lymphoma occurring in the central nervous system is considered primary central nervous system lymphoma (PCNSL), usually without systematic lesions. Over the last few decades, a deep understanding of PCNSL has been lacking due to the low incidence rate, and the overall survival and progression-free survival of patients with PCNSL are lower than those with other types of non-Hodgkin lymphoma. Recently, there have been several advancements in research on PCNSL. Advances in diagnosis of the disease are primarily reflected in the promising diagnostic efficiency of novel biomarkers. Pathogenesis mainly involves abnormal activation of nuclear factor kappa-B signaling pathways, copy number variations, and DNA methylation. Novel therapies such as Bruton's tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, and phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors are being evaluated as possible treatment options for PCNSL, especially for relapsed/refractory (R/R) cases. Several clinical trials also indicated the promising feasibility and efficacy of chimeric antigen receptor T-cell therapy for selected R/R PCNSL patients. This review focuses on discussing recent updates, including the diagnosis, pathogenesis, and novel therapy of PCNSL.

The advanced lung cancer inflammation index is associated with mortality in peritoneal dialysis patients.

BACKGROUND: There is still a very high morbidity and mortality rate for patients undergoing peritoneal dialysis (PD). The advanced lung cancer inflammation index (ALI) has been demonstrated to be associated with the prognosis in multiple types of cancers. Like in cancer, systemic chronic low-grade inflammation is one of the distinguishing features of PD patients. Therefore, we aimed to investigate the relationships between the ALI and all-cause and cardiovascular disease (CVD) mortality in PD patients. METHODS: Patients who started PD at Shaoxing People's Hospital between 1 January 2013 and 31 December 2020 (n = 277) were recruited and followed up until 1 July 2023. They were divided into high-ALI group and low-ALI group according to the median of ALI. Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the associations between the ALI and all-cause and CVD mortality. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to determine the predictive power of the ALI for all- cause and CVD mortality. RESULTS: During the median follow-up of 40.50 months (interquartile range, 26.42-59.77 months), a total of 55 patients died, 31 of whom died due to CVD. Kaplan-Meier curves revealed that patients in the low-ALI group had significantly lower cumulative and cardiovascular cumulative survival rates than did those in the high-ALI group (all P < 0.001). After we corrected for confounders, the risk of all-cause and CVD mortality was significantly greater in the low-ALI group than in the high-ALI group [hazard ratio (HR) 1.944, 95% confidence interval (CI) 1.068-3.540, P = 0.030, and HR 2.672, 95% CI 1.188-6.009, P = 0.017, respectively]. The predictive value of ALI (AUC = 0.708, 95% CI 0.630-0.786, P < 0.001) for all-cause mortality was superior to albumin (AUC = 0.644, 95% CI 0.556-0.726, P < 0.001), body mass index (AUC = 0.581, 95% CI 0.496-0.659, P = 0.069) and neutrophil-to-lymphocyte ratio (AUC = 0.675, 95% CI 0.596-0.754, P < 0.001). CONCLUSION: A lower ALI is an independent risk factor for all-cause and cardiovascular mortality in PD patients. The ALI may be an effective indicator for predicting outcomes in PD patients.

Unraveling the role of LDHA and VEGFA in oxidative stress: A pathway to therapeutic interventions in cerebral aneurysms.

Cerebral aneurysms (CA) are critical conditions often associated with oxidative stress in vascular endothelial cells (VECs). The enzyme lactate dehydrogenase A (LDHA) plays a crucial role in glycolysis and lactate metabolism, processes implicated in the pathogenesis of aneurysms. Understanding these molecular mechanisms can inform the development of novel therapeutic targets. This study investigated the role of lactate metabolism and lactate-related genes, particularly LDHA and vascular endothelial growth factor A (VEGFA) genes, in VECs during oxidative stress. Using the GSE26969 dataset, we identified differential expression of lactate-related genes and performed functional enrichment analysis, revealing significant associations with glycolysis and lactate metabolic pathways. To induce oxidative stress, VECs were treated with H2O2, and the expression of LDHA and VEGFA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) assays. Under oxygen-glucose deprivation/reperfusion (OGD/R) conditions, the effects of LDHA overexpression and VEGFA knockdown on cell viability and apoptosis were evaluated. Immunoprecipitation combined with western blotting was used to detect the lactylation status of LDHA following OGD/R stimulation and treatment with lactic acid (LA) and 2-deoxyglucose (2-DG). Our results indicated that oxidative stress modulates LDHA expression, glucose uptake, and lactate production, suggesting a metabolic shift towards glycolysis. LDHA overexpression improved cell survival and reduced apoptosis, while VEGFA knockdown had the opposite effect. Additionally, 2-DG treatment reduced LDHA lactylation and apoptosis. Our findings demonstrated that LDHA plays a critical role in the oxidative stress response of VECs, highlighting the potential therapeutic value of targeting glycolysis in CA. This study contributes to the understanding of metabolic adaptations in vascular pathologies and suggests new avenues for therapeutic intervention in CA management.

High-precision Helicobacter pylori infection diagnosis using a dual-element multimodal gas sensor array.

Helicobacter pylori (H. pylori) is a globally widespread bacterial infection. Early diagnosis of this infection is vital for public and individual health. Prevalent diagnosis methods like the isotope 13C or 14C labelled urea breath test (UBT) are not convenient and may do harm to the human body. The use of cross-response gas sensor arrays (GSAs) is an alternative way for label-free detection of metabolite changes in exhaled breath (EB). However, conventional GSAs are complex to prepare, lack reliability, and fail to discriminate subtle changes in EB due to the use of numerous sensing elements and single dimensional signal. This work presents a dual-element multimodal GSA empowered with multimodal sensing signals including conductance (G), capacitance (C), and dissipation factor (DF) to improve the ability for gas recognition and H. pylori-infection diagnosis. Sensitized by poly(diallyldimethylammonium chloride) (PDDA) and the metal-organic framework material NH2-UiO66, the dual-element graphene oxide (GO)-composite GSAs exhibited a high specific surface area and abundant adsorption sites, resulting in high sensitivity, repeatability, and fast response/recovery speed in all three signals. The multimodal sensing signals with rich sensing features allowed the GSA to detect various physicochemical properties of gas analytes, such as charge transfer and polarization ability, enhancing the sensing capabilities for gas discrimination. The dual-element GSA could differentiate different typical standard gases and non-dehumidified EB samples, demonstrating the advantages in EB analysis. In a case-control clinical study on 52 clinical EB samples, the diagnosis model based on the multimodal GSA achieved an accuracy of 94.1%, a sensitivity of 100%, and a specificity of 90.9% for diagnosing H. pylori infection, offering a promising strategy for developing an accurate, non-invasive and label-free method for disease diagnosis.

The autophagic regulation of rosiglitazone-promoted adipocyte browning.

Objective: Browning of white adipocytes is considered an efficient approach to combat obesity. Rosiglitazone induces the thermogenetic program of white adipocytes, but the underlying mechanisms remain elusive. Methods: Expression levels of browning and autophagy flux markers were detected by real-time PCR and immunoblotting. H&E and Oil Red O staining were performed to evaluate the lipid droplets area. Nuclear protein extraction and immunoprecipitation were used to detect the proteins interaction. Results: In this study, we reported that rosiglitazone promoted adipocyte browning and inhibited autophagy. Rapamycin, an autophagy inducer, reversed adipocyte browning induced by rosiglitazone. Autophagy inhibition by rosiglitazone does not prevent mitochondrial clearance, which was considered to promote adipose whitening. Instead, autophagy inhibition increased p62 nuclear translocation and stabilized the PPARγ-RXRα heterodimer, which is an essential transcription factor for adipocyte browning. We found that rosiglitazone activated NRF2 in mature adipocytes. Inhibition of NRF2 by ML385 reversed autophagy inhibition and the pro-browning effect of rosiglitazone. Conclusion: Our study linked autophagy inhibition with rosiglitazone-promoted browning of adipocytes and provided a mechanistic insight into the pharmacological effects of rosiglitazone.

Mitochondrial outer membrane protein Samm50 protects against hypoxia-induced cardiac injury by interacting with Shmt2.

Cardiac remodeling is a critical process following myocardial infarction (MI), potentially leading to heart failure if untreated. The significance of mitochondrial homeostasis in MI remains insufficiently understood. Samm50 is an essential component of mitochondria. Our study aimed to investigate its role in hypoxia-induced cardiac injury and the underlying mechanisms. First, we observed that Samm50 was dynamically downregulated in mice with MI compared to the control mice. In vitro, Samm50 was also downregulated in oxygen-glucose-deprived neonatal rat cardiomyocytes and fibroblasts. Overexpression and knockdown of Samm50 mitigated and exacerbated cardiac apoptosis and fibrosis, while also improving and worsening mitochondrial homeostasis, respectively. Protein interactions with Samm50 during the protective process were identified via immune-coprecipitation/mass spectroscopy. Mechanistically, serine hydroxymethyltransferase 2 (Shmt2) interacted with Samm50, acting as a crucial element in the protective process by hindering the transfer of Bax from the cytoplasm to the mitochondria and subsequent activation of caspase-3. Inhibition of Shmt2 diminished the protective effect of Samm50 overexpression against cardiac injury. Finally, Samm50 overexpression in vivo mitigated cardiac remodeling and enhanced cardiac function in both acute and chronic MI. In conclusion, Samm50 overexpression mitigated hypoxia-induced cardiac remodeling by inhibiting apoptosis and fibrosis, with Shmt2 acting as a key regulator in this protective process. The Samm50/Shmt2 axis represents a newly discovered mitochondria-related pathway for mitigating hypoxia-induced cardiac injury.

Geniposide effectively safeguards HT22 cells against Aß-induced damage by activating mitophagy via the PINK1/Parkin signaling pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (Aß) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides, is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on Aß25-35-induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkin-mediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by Aß25-35. Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by Aß25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by Aß25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.