A Homogeneous Janus Membrane Based on Functionalized MOFs Crosslinked by Aramid Nanofibers for Quasi-Solid-State Lithium Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are considered as promising candidates in the next generation of high energy density devices. However, the serious shuttle effect, irreversible dendrite growth of Li metal anode, and the potential safety hazard impede the practical application of LSBs. Herein, a novel homogeneous Janus membrane based on functionalized MOFs crosslinked by aramid nanofibers is designed and synthesized to simultaneously solve the above challenges in quasi-solid-state LSBs. The aramid nanofibers with good mechanical properties and thermal stability act as a homogeneous scaffold to crosslink the MOF particles with different ligands on both sides and this Janus membrane upgrades the stability and safety on both the cathode and anode. Specifically, the amino ligand-decorated MOFs contribute to homogenize Li-ion flux and stabilize the lithium anode, and the sulfonic ligand-decorated MOFs effectively suppress the shuttle effect by the dual effects of chemical adsorption and electrostatic repulsion. The quasi-solid-state LSBs assembled with this homogeneous Janus membrane deliver excellent rate performance and cycling stability. Moreover, it exhibits a high initial capacity of 923.4 mAh g-1 at 1 C at 70 °C, and 697.3 mAh g-1 is retained after 100 cycles, indicating great potential for its application in high-safety LSBs.

APOE Genotype Modifies the Association between Midlife Adherence to the Planetary Healthy Diet and Cognitive Function in Later Life among Chinese Adults in Singapore.

BACKGROUND: It remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype. OBJECTIVES: We aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE ε4 allele could modify this association. METHODS: The study included 16,736 participants from the Singapore Chinese Health Study. The PHD score was calculated using data from a validated 165-item food frequency questionnaire at baseline (1993-1998), with higher scores indicating greater adherence to the PHD. Cognitive function was assessed by the Singapore-modified Mini-Mental State Examination at follow-up 3 visits (2014-2016). A subset of 9313 participants had APOE genotype data. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders. RESULTS: We identified 2397 (14.3%) cases of poor cognitive function. In the total population, OR (95% CI) of poor cognitive function for each one-SD increment in the PHD score was 0.89 (0.85, 0.93). Carriers of APOE ε4 allele had increased risk of poor cognitive function (OR: 1.36, 95% CI: 1.15, 1.61). There was a significant interaction between the PHD score and the APOE ε4 allele (P-interaction = 0.042). Each one-SD increment in the PHD score was significantly associated with lower risk of poor cognitive function (OR: 0.89; 95% CI: 0.83, 0.96) in non-carriers of APOE ε4 allele, but not in APOE ε4 allele carriers (OR: 1.04, 95% CI: 0.89, 1.23). CONCLUSIONS: Midlife adherence to the PHD was associated with reduced risk of poor cognitive function in later life. However, this was not observed in carriers of APOE ε4 allele who had higher risk of poor cognitive function.

Analysis of the Correlation and Prognostic Significance of Tertiary Lymphoid Structures in Breast Cancer: A Radiomics-Clinical Integration Approach.

BACKGROUND: Tertiary lymphoid structures (TLSs) are potential prognostic indicators. Radiomics may help reduce unnecessary invasive operations. PURPOSE: To analyze the association between TLSs and prognosis, and to establish a nomogram model to evaluate the expression of TLSs in breast cancer (BC) patients. STUDY TYPE: Retrospective. POPULATION: Two hundred forty-two patients with localized primary BC (confirmed by surgery) were divided into BC + TLS group (N = 122) and BC - TLS group (N = 120). FIELD STRENGTH/SEQUENCE: 3.0T; Caipirinha-Dixon-TWIST-volume interpolated breath-hold sequence for dynamic contrast-enhanced (DCE) MRI and inversion-recovery turbo spin echo sequence for T2-weighted imaging (T2WI). ASSESSMENT: Three models for differentiating BC + TLS and BC - TLS were developed: 1) a clinical model, 2) a radiomics signature model, and 3) a combined clinical and radiomics (nomogram) model. The overall survival (OS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were compared to evaluate the prognostic value of TLSs. STATISTICAL TESTS: LASSO algorithm and ANOVA were used to select highly correlated features. Clinical relevant variables were identified by multivariable logistic regression. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), and through decision curve analysis (DCA). The Kaplan-Meier method was used to calculate the survival rate. RESULTS: The radiomics signature model (training: AUC 0.766; test: AUC 0.749) and the nomogram model (training: AUC 0.820; test: AUC 0.749) showed better validation performance than the clinical model. DCA showed that the nomogram model had a higher net benefit than the other models. The median follow-up time was 52 months. While there was no significant difference in 3-year OS (P = 0.22) between BC + TLS and BC - TLS patients, there were significant differences in 3-year DFS and 3-year DMFS between the two groups. DATA CONCLUSION: The nomogram model performs well in distinguishing the presence or absence of TLS. BC + TLS patients had higher long-term disease control rates and better prognoses than those without TLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography.

The proline biosynthetic enzyme Δ1-pyrroline-5-carboxylate (P5C) reductase 1 (PYCR1) is one of the most consistently upregulated enzymes across multiple cancer types and central to the metabolic rewiring of cancer cells. Herein, we describe a fragment-based, structure-first approach to the discovery of PYCR1 inhibitors. Thirty-seven fragment-like carboxylic acids in the molecular weight range of 143-289 Da were selected from docking and then screened using X-ray crystallography as the primary assay. Strong electron density was observed for eight compounds, corresponding to a crystallographic hit rate of 22%. The fragments are novel compared to existing proline analog inhibitors in that they block both the P5C substrate pocket and the NAD(P)H binding site. Four hits showed inhibition of PYCR1 in kinetic assays, and one has lower apparent IC50 than the current best proline analog inhibitor. These results show proof-of-concept for our inhibitor discovery approach and provide a basis for fragment-to-lead optimization.

Brassisterol A, a new ergosterol from co-cultivation of fungi attenuates neuroinflammation via targeting NLRP3/caspase-1/GSDMD pathway.

Three new ergosterol derivatives brassisterol A-C (1-3) and two new epimeric bicycle-lactones brassictones A and B (4 and 5), were isolated from the co-cultivation of Alternaria brassicicola and Penicillium granulatum. The absolute configurations of these isolates were confirmed by extensive NMR spectra, TD-DFT ECD calculation, and the single crystal XRD data analysis. Amongst the metabolites, compound 1 exhibited potential anti-Parkinson's disease activity in both MPTP-induced zebrafish and MPP+-induced SH-SY5Y cells. Molecular mechanism studies in vitro showed that 1 attenuated the increase of α-synuclein, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and GSDMD expression in the MPP+ induced PD model. Molecular docking in silico simulations exhibited that 1 was well accommodated to one of the binding pockets of NLRP3 8ETR in an appropriate conformation via forming typical hydrogen bonds as well as possessing a high negative binding affinity (-8.97 kcal/mol). Thus, our work suggested that 1 protected dopaminergic cell from neuroinflammation via targeting NLRP3/caspase-1/GSDMD signaling pathway.

Prioritized single vitrified blastocyst to be warmed between grades 3 or 4 blastocyst on day 5 transfer cycles.

PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.

Prognosis of urgent initiation of peritoneal dialysis: a systematic review and meta-analysis.

OBJECTIVES: Currently, there is no consensus on the optimal timing for the initiation of peritoneal dialysis (PD) after catheter placement. DESIGN: Systematic review and meta-analysis. EXACT DATE OF DATA COLLECTION: From inception till July 31, 2023. MAIN OUTCOME MEASURES: To assess the outcomes and safety of unplanned PD initiation (<14/7 days after catheter insertion) in cohort studies. RESULTS: Fifteen studies involving 3054 participants were included. (1) The risk of unplanned initiation of leakage and Obstruction was no difference in both the break-in period (BI) <14 and BI < 7 groups. (2) Catheter displacement was more likely to occur in the emergency initiation group with BI < 7. (3) No significant differences were observed between the two groups regarding infectious complications. (4) There was no difference in transition to HD between patients with BI < 7 and BI < 14 d. CONCLUSION: Infectious complications of unplanned initiation of peritoneal dialysis did not differ from planned initiation. Emergency initiation in the BI < 7 group had higher catheter displacement, but heterogeneity was higher. There were no differences in leakage or obstruction in either group. Catheter survival was the same for emergency initiation of peritoneal dialysis compared with planned initiation of peritoneal dialysis and did not increase the risk of conversion to hemodialysis. REGISTRATION: This meta-analysis was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023431369).

Effects of exercise on depression in patients with rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of exercise intervention on depression in rheumatic diseases by means of a meta-analysis. METHODS: The Cochrane Library, Embase, Medline, PubMed, and relevant records were searched. The qualities of randomized controlled trials were evaluated. Meta-analysis of the obtained related data was completed using RevMan 5.3. Heterogeneity was also evaluated with χ2 test and I2. RESULTS: Twelve RCTs were reviewed. Compared with baseline, the meta-analysis results showed that there was significant difference in the improvement of depression assessed by HADs, BDI, CES­D, and AIMS in patients with rheumatic diseases (post exercise vs. baseline, -0.73 [-1.05, -0.4], P < 0.0001, I2 = 0%). In subgroup analysis, although none of these trends in BDI and CES­D subgroups were significant at P < 0.05, there were clear trends towards improvement in depression. CONCLUSION: As an alternative or supplementary treatment, the effect of exercise on rheumatism is obvious. Rheumatologists can consider exercise as an integral part of the treatment of patients with rheumatism.

Clinicopathological features of rhabdomyosarcoma with novel FET::TFCP2 and TIMP3::ALK fusion: report of two cases and literature review.

AIMS: The aim of this study was to evaluate the clinicopathological features, immunophenotype, differential diagnosis, molecular genetic features and prognosis of spindle cell rhabdomyosarcoma with TFCP2 rearrangement. METHODS: Two cases of spindle cell rhabdomyosarcoma with FET::TFCP2 gene fusion were included in this study. Samples were collected and evaluated through histological observation, immunohistochemistry, fluorescence in-situ hybridisation and high-throughput gene sequencing and previous findings. RESULTS: The tumour tissues mainly comprised spindle cells and epithelioid cells, which expressed striated muscle markers, and exhibited high expression levels of CK and ALK protein markers. Molecular detection showed that the FET::TFCP2 gene was fused. A rare case with TIMP3::ALK and FUS::TFCP2 double-fusion was observed in this study. CONCLUSIONS: A case with double fusion of ALK and TFCP2 was reported in rhabdomyosarcoma for the first time in this study, which provides information on the molecular characteristic of the tumour. Spindle cell rhabdomyosarcoma with FET::TFCP2 fusion is characterised by histological, immunohistochemical and genetic changes. The tumour is aggressive, with poor prognosis and poor response to radiotherapy and chemotherapy. The efficacy of targeted therapy for ALK should be explored through more clinical studies.

Expression profiles of circular RNAs in spermatozoa from aging men.

BACKGROUND: Advanced paternal age (APA) is associated with decreased fertility, but the mechanism underlying APA remains unknown. CircRNAs have been reported to be ideal candidate biomarkers for diagnostic and therapeutic applications in many diseases and are also involved in spermatogenesis. Hence, we aimed to assess the circRNA expression profile of spermatozoa from aging men. METHODS AND RESULTS: We recruited 6 subjects, including 3 in the younger group (men age < 40) and 3 in the APA group (men age ≥ 40). RNA sequencing was exploited to identify the expression profiles of circRNAs between the two groups. The expression levels of circRNAs were validated using real-time quantitative polymerase chain reaction (RT-qPCR). Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology analysis were performed to evaluate the functions of differentially expressed circRNAs (DE-circRNAs) between the two groups. In total, 18,787 circRNAs were sequenced in the spermatozoa of two groups. Our analysis revealed that there were 1056 downregulated circRNAs and 1228 upregulated circRNAs between the two groups, and KEGG analysis showed they were mainly involved in pathways including the DNA repair signaling pathway, meiotic recombination signaling pathway, and PI3K/AKT signaling pathway. CONCLUSIONS: In conclusion, our study suggested that circRNAs play a vital role in spermatozoa from aging men and provided a fresh perspective on the specific regulatory mechanism of spermatozoa from aging men.

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis.

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1ß, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1ß, IL-8 and TNF-α) and RF (BUN, Scr, ß2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.

HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.

Graphene Oxide-Based Highly Sensitive Assay of Circulating MicroRNAs for Early Prediction of the Response to Neoadjuvant Chemotherapy in Breast Cancer.

The response to neoadjuvant chemotherapy (NAC) is highly correlated with survival in breast cancer (BC) patients. The early prediction of the response to NAC could facilitate treatment adjustments on a patient-by-patient basis, which would improve patient outcomes and survival. Conventional techniques used for detecting circulating microRNAs (miRNAs), which act as biomarkers for the early prediction of NAC efficacy in BC patients, are associated with limitations such as low sensitivity and specificity. We designed a highly sensitive graphene oxide (GO)-based qRT-PCR method for detecting miRNAs associated with the chemotherapeutic response in BC patients. The results showed that miRNA levels at both the baseline and end of the first NAC cycle could help distinguish NAC responders from NAC nonresponders; BC patients with lower plasma miRNA levels were more likely to achieve pathological complete remission. Thus, GO-based qRT-PCR could facilitate early prediction of NAC efficacy in BC patients.

Iptakalim alleviates synaptic damages via targeting mitochondrial ATP-sensitive potassium channel in depression.

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive-like phenotype in vivo (chronic mild stress-induced mice model of depression) and in vitro (corticosterone-induced cellular model). Further study showed that Ipt could upregulate the synaptic-related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP-sensitive potassium (Mito-KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.

Iptakalim improves cerebral microcirculation in mice after ischemic stroke by inhibiting pericyte contraction.

Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 µM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Accuracy of the spontaneous breathing trial using a combined CPAP + PSV model to predict extubation outcomes in very preterm infants.

BACKGROUND: Very preterm infants often require mechanical ventilation. However, objective criteria to predict the outcomes of extubation in very premature neonates remain lacking. The aim of this study was to investigate the accuracy of the spontaneous breathing trial (SBT) using a combined model of continuous positive airway pressure (CPAP) and low-level pressure support ventilation (PSV) to predict the extubation outcomes of preterm infants with gestational age < 32 weeks. METHODS: Preterm infants with gestational age < 32 weeks, birth weight < 1500 g and requiring mechanical ventilation were selected for the study. All infants underwent a 10-minute SBT using CPAP combined with low-level PSV prior to the planned extubation. Then, the infants were extubated within 1 h after SBT. The outcomes of extubation were considered successful if the neonates did not require reintubation 72 h after extubation. RESULTS: A total of 119 eligible preterm infants were enrolled in the study, with a median gestational age of 28.9 (27.1-30.3) weeks and a median birth weight of 1100 (900-1350) g. In total, 101 of all infants had successful extubation, 18 of whom failed and eventually had to be reintubated. Of the 102 infants who achieved SBT, 99 were successfully extubated, and 15 of the 17 infants who did not pass SBT had failed extubation. Finally, the diagnostic value for SBT could be assessed with a sensitivity of 98%, a specificity of 83.3%, a positive predictive value of 97.1% and a negative predictive value of 88.2%. CONCLUSION: SBT using a combined CPAP + low-level PSV model can predict the outcomes of extubation in very preterm infants with high sensitivity and specificity.

Activating PPARß/δ Protects against Endoplasmic Reticulum Stress-Induced Astrocytic Apoptosis via UCP2-Dependent Mitophagy in Depressive Model.

As energy metabolism regulation factor, peroxisome proliferator-activated receptor (PPAR) is thought to be a potential target for the treatment of depression. The present study was performed to evaluate the effects of activating PPARß/δ, the most highly expressed subtype in the brain, in depressive in vivo and in vitro models. We observed that PPARß/δ agonist GW0742 significantly alleviated depressive behaviors in mice and promoted the formation of autophagosomes around the damaged mitochondria in hippocampal astrocytes. Our in vitro experiments showed that GW0742 could reduce mitochondrial oxidative stress, and thereby attenuate endoplasmic reticulum (ER) stress-mediated apoptosis pathway via inhibiting IRE1α phosphorylation, subsequently protect against astrocytic apoptosis and loss. Furthermore, we found that PPARß/δ agonist induces astrocytic mitophagy companied with the upregulated UCP2 expressions. Knocking down UCP2 in astrocytes could block the anti-apoptosis and pro-mitophagy effects of GW0742. In conclusion, our findings reveal PPARß/δ activation protects against ER stress-induced astrocytic apoptosis via enhancing UCP2-mediated mitophagy, which contribute to the anti-depressive action. The present study provides a new insight for depression therapy.

Urban flood resilience assessment using RAGA-PP and KL-TOPSIS model based on PSR framework: A case study of Jiangsu province, China.

The research on urban flood resilience will contribute to building a more resilient city and provide valuable reference for municipal decision-makers. There are many frameworks and approaches for empirical studies on what constitutes urban flood resilience and how to evaluate it. In this study, a typical region suffering from flood disaster in China-Jiangsu Province was selected as the study area, including 13 prefecture-level cities. The pressure-state-response (PSR) framework, the projection pursuit based on real-coded accelerated genetic algorithm (RAGA-PP) and the technique for order preference by similarity to an ideal solution based on the Kullback-Leibler distance (KL-TOPSIS) were combined to develop a hybrid multi-criteria approach for assessing urban flood resilience. Then the grey relational analysis obtained the important factors. The results illustrate that (1) the development of each subsystem in the city is uncoordinated, that is, the pressure-subsystem has little influence on urban flood resilience, while the state-subsystem and the response-subsystem have great influence. (2) The urban flood resilience in Jiangsu Province presents obvious polarization trend, that is, Southern Jiangsu is more resilient than Northern Jiangsu. The underlying factors are closely related to the level of economic development. Furthermore, the proposed method provides a practical evaluation approach for other fields.

The therapeutic role of mesenchymal stem cell-derived exosomes in the autoimmune diseases.

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.