Lead Isolation and Capture in Perovskite Photovoltaics toward Eco-Friendly Commercialization.

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

Association of composite dietary antioxidant index with prevalence of stroke: insights from NHANES 1999-2018.

Background: There is a growing acknowledgment of the potential influence of antioxidative effects resulting from dietary decisions on the occurrence of stroke. The objective of this study was to elucidate the correlation between the composite dietary antioxidant index (CDAI) and the incidence of stroke in the general population of the United States. Methods: We gathered cross-sectional data encompassing 40,320 participants from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Employing weighted multivariate logistic regression, we assessed the correlation between CDAI and stroke, while also investigating potential nonlinear relationships through restricted cubic spline (RCS) regression. Further, the intake of CDAI components were then incorporated into a predictive nomogram model, subsequently evaluated for its discriminatory prowess in stroke risk assessment using the receiver operating characteristic (ROC) curve. Results: Post-adjustment for confounding variables, we found that higher CDAI score were associated with a decreased risk of stroke, the odds ratio (OR) [95% CI] of CDAI associating with prevalence was 0.96 [0.94-0.98] (P< 0.001). Moreover, the adjusted OR [95% CI] for stroke across ascending CDAI quartiles stood at 0.90 [0.74-1.09], 0.74 [0.60-0.91], and 0.61 [0.50-0.76] compared to the reference quartile, respectively. The RCS analysis indicated a nonlinear yet negative correlation between CDAI and stroke. The nomogram model, constructed based the intake of antioxidants, exhibited a significant predictive capacity for stroke risk, boasting an area under the curve (AUC) of 77.4% (76.3%-78.5%). Conclusion: Our investigation ascertained a nonlinear negative relationship between CDAI and stroke within the broader American population. However, given the inherent limitations of the cross-sectional design, further comprehensive research is imperative to establish the causative nature of this association.

Electronically Manipulated Molecular Strategy Enabling Highly Efficient Tin Perovskite Photovoltaics.

Buried interface modification can effectively improve the compatibility between interfaces. Given the distinct interface selections in perovskite solar cells (PSCs), the applicability of a singular modification material remains limited. Consequently, in response to this challenge, we devised a tailored molecular strategy based on the electronic effects of specific functional groups. Therefore, we prepared three distinct silane coupling agents, and due to the varying inductive effects of these functional groups, the electronic distribution and molecular dipole moments of the coupling agents are correspondingly altered. Among them, trimethoxy (3,3,3-trifluoropropyl)-silane (F3 -TMOS), which possesses electron-withdrawing groups, generates a molecular dipole moment directed toward the hole transport layer (HTL). This approach changes the work function of the HTL, optimizes the energy level alignment, reduces the open-circuit voltage loss, and facilitates carrier transport. Furthermore, through the buffering effect of the coupling agent, the interface strain and lattice distortion caused by annealing the perovskite are reduced, enhancing the stability of the tin-based perovskite. Encouragingly, tin PSCs treated with F3 -TMOS achieved a champion efficiency of 14.67 %. This strategy provides an expedient avenue for the design of buried interface modification materials, enabling precise molecular adjustments in accordance with distinct interfacial contexts to ameliorate mismatched energetics and enhance carrier dynamics.

mPGES-2 blockade antagonizes ß-cell senescence to ameliorate diabetes by acting on NR4A1.

ß-cell dysfunction is a hallmark of type 1 and type 2 diabetes. Type 2 diabetes is strongly associated with ageing-related ß-cell abnormalities that arise through unknown mechanisms. Here we show better ß-cell identity, less ß-cell senescence, enhanced glucose-stimulated insulin secretion and improved glucose homeostasis in global microsomal prostaglandin E synthase-2 (mPGES-2)-deficient mice challenged with a high-fat diet or bred with a genetic model of type 2 diabetes (db/db mice). Furthermore, the function of mPGES-2 in ß-cells is validated using mice with ß-cell-specific mPGES-2 deficiency or overexpression. Mechanistically, the protective role of mPGES-2 deletion is induced by antagonizing ß-cell senescence via interference of the PGE2-EP3-NR4A1 signalling axis. We also discover an inhibitor of mPGES-2, SZ0232, which protects against ß-cell dysfunction and diabetes, similar to mPGES-2 deletion. We conclude that mPGES-2 contributes to ageing-associated ß-cell senescence and dysfunction via the PGE2-EP3-NR4A1 signalling axis. Pharmacologic blockade of mPGES-2 might be effective for treating ageing-associated ß-cell dysfunction and diabetes.

Efficacy of Moxifloxacin against Mycobacterium abscessus in Zebrafish Model in vivo.

OBJECTIVE: Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. METHODS: A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. RESULTS: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. CONCLUSION: MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is the main cause of acute liver failure. This study investigated the role of microsomal prostaglandin E synthase 2 (mPGES-2), discovered as one of the prostaglandin E2 (PGE2) synthases, in mediating APAP-induced liver injury. Using mPGES-2 wild-type (WT) and knockout (KO) mice, marked resistance to APAP-induced liver damage was found in mPGES-2 KO, as indicated by robust improvement of liver histology, changes in liver enzyme release, and marked decrease in APAP-cysteine adducts (APAP-CYS) and inflammatory markers. Moreover, the results confirmed that increase in liver PGE2 content in KO mice under basal conditions was not critical for the protection from APAP-induced liver injury. Importantly, mPGES-2 deletion inhibited the production of malondialdehyde (MDA), increasing glutathione (GSH) level. Enhanced GSH level may contribute to the inhibition of APAP toxicity in mPGES-2 KO mice. To further elucidate the role of mPGES-2 in the liver injury induced by APAP, adeno-associated viruses (AAV) were used to overexpress mPGES-2 in the liver. The results showed that mPGES-2 overexpression aggravates liver injury associated with an increase in inflammatory markers and chemokines after APAP treatment. Moreover, a lower level of GSH was detected in the mPGES-2 overexpression group compared to the control group. Collectively, our findings indicate that mPGES-2 plays a critical role in regulating APAP-induced liver injury, possibly by regulating GSH and APAP-CYS level, which may provide a potential therapeutic strategy for the prevention and treatment of APAP-induced liver injury.

[MicroRNA-3963 Promotes Adipogenic Differentiation of Mouse-Derived Mesenchymal Stem Cells].

OBJECTIVE: To investigate the effect of MicroRNA-3963(miR-3963) on the adipogenic differentiation of mouse bone-derived mesenchymal stem cells(MSC). METHODS: MSCs were isolated from C57BL/6 mice bone fragment and transfected with miR-3963 mimic, miR-3963 inhibitor and negative control. The expression of miR-3963 and transfection efficiency were detected by q-PCR. These transfected cells were induced to adipocytes and stained with oil red O after 14 days culture. q-PCR and Western blot were used to detect the expression of adipogenic differentiation marker genes C/EBPα and PPARγ at transcriptional level and protein level. RESULTS: The results of q-PCR revealed that miR-3963 expression level was up-regulated after transfection with miR-3963 mimic (P<0.0001), and down-regulated after transfection with miR-3963 inhibitor (P<0.0001). After oil red staining, overexpression of miR-3963 in MSCs could promote the formation of lipid droplet. The q-PCR and Western blot analyses showed the significant increase of expression of adipogenic marker genes C/EBPα and PPARγ in MSC transfected with miR-3963 mimic. Additionally, compared with the control group, miR-3963 inhibitor could decrease adipogenic differentiation of MSC. CONCLUSION: miR-3963 can regulate and promote adipogenic differentiation of mouse bone-derived MSC.

Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a polycystic kidney disease mouse model.

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney. There is an urgent need to develop effective ADPKD therapies. We used an in vitro Madin-Darby canine kidney (MDCK) cyst model and a murine embryonic kidney cyst model to evaluate whether quercetin inhibits cyst development. We then used a polycystic kidney disease (PKD) mouse model to further determine the in vivo effects of quercetin (100 mg per kg body weight twice per day) on PKD mice via subcutaneous injections. The results show that quercetin significantly and dose-dependently inhibited cyst formation and enlargement in the MDCK cyst and embryonic kidney cyst models. Quercetin also noticeably reduced the cystic index in PKD mice. Furthermore, the effective dose of quercetin did not cause cytotoxicity in MDCK cells. Quercetin treatment decreased the levels of intracellular signalling proteins in PKD mouse kidneys, including phosphorylated protein kinase B (also known as AKT) and phosphorylated extracellular signal-regulated kinase (ERK), which are upregulated and promote cyst development in ADPKD. Quercetin also reversed E-cadherin expression, which is localized in normal proximal tubules in PKD mouse kidneys. Taken together, these results demonstrate that quercetin hinders renal cyst development in vivo and in vitro and represents a novel candidate strategy for the treatment of ADPKD.

Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities. The aim of this study was to investigate the therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism. We established a mouse model of NAFLD using a high-fat diet (HFD), and injected the mice with different doses of mangiferin (15, 30, and 60mg/kg, intraperitoneal) for 12 weeks. Liver tissue was assessed to evaluate changes in inflammatory responses, autophagy, and glycolipid metabolism. We found that mangiferin decreased body weight, as well as the levels of triglycerides and total cholesterol in plasma and the liver. It also increased glucose tolerance in HFD-fed mice. In addition, mangiferin decreased inflammatory responses by inhibiting the activities of nuclear factor kappa B and c-Jun N-terminal kinase, regulated autophagy via the AMP-activated protein kinase/mechanistic target of rapamycin signaling pathway, and improved glycolipid metabolism via modulation of the insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B signaling pathway. This study demonstrated that mangiferin significantly ameliorates NAFLD development in HFD-fed mice by inhibiting inflammatory responses, activating autophagy, and improving glycolipid metabolism.

Role of miRNA-1 in regulating connexin 43 in ischemia-reperfusion heart injury: a rat model.

MiRNA-1 may participate in regulating ischemia-reperfusion injury (IRI) by affecting the expression and distribution of connexin 43 (Cx43). The aim of this study is to investigate miR-1 expression and its potential role in regulating Cx43 during ischemic postconditioning (IPOST) in a rat model. Fifty-five Wistar male rats were randomly divided into five groups: N, IR, IPOST, agomir-1, and antagomir-1 group. The hearts were perfused with the Langendorff system. The reperfusion arrhythmia (RA) and myocardial infarct size were observed and recorded. The miRNA-1 expression and the Cx43 expression and distribution were assessed by RT-PCR, immunoblotting, and immunohistochemistry. First, the RA score in the IR group was higher than that in the control group, whereas there was no difference between the IPOST and antagomir-1 groups. Second, the myocardial infarct size was larger in the agomir-1 than in the IPOST group; there was no difference between the antagomir-1 and the IPOST group. Third, the miRNA-1 expression increased by 78% in the agomir-1 group but decreased by 32% in the antagomir-1 group compared with the IPOST group. Fourth, compared with the Control group, the Cx43 expression in the IR group decreased, the Cx43 expression decreased in the agomir-1 group compared with the IPOST group. Fifth, the distribution of Cx43 was irregular and disorganized in the IR and agomir-1 groups. In the IPOST and antagomir-1 groups, Cx43 was neatly distributed in the intercalated disk area. Our findings suggest that IPOST can inhibit the up-regulation of miRNA-1 induced by ischemia-reperfusion and that the down-regulation of miRNA-1 can prevent the decrease and redistribution of Cx43, which will protect the heart from IRI.