Iron Oxide Clusters as Electron Donors Under Light Enhance Oxygen Reduction Kinetics at Atomically Dispersed Fe for Photocatalytic CH4 Partial Oxidation.

Photocatalytic CH4 oxidation to CH3OH emerges as a promising strategy to sustainably utilize natural gas and mitigate the greenhouse effect. However, there remains a significant challenge for the synthesis of methanol by using O2 at low temperature. Inspired by the catalytic structure in soluble methane monooxygenase (MMO) and the corresponding reaction mechanism, we prepared a biomimetic photocatalysts with the decoration of Fe2O3 nanocluster and satellite Fe single atom immobilized on carbon nitride. The catalyst demonstrates an excellent CH3OH productivity of 5.02 mmol·gcat-1·h-1 with methanol selectivity of 98.5%. Mechanism studies reveal that the synergy between Fe2O3 nanocluster and Fe single atom establishes a dual-Fe site as MMO for O2 activation and subsequent CH4 partial oxidation. Moreover, the light excitation of Fe2O3 nanoclusters with a relative narrow bandgap could deliver the electrons and protons to atomic Fe that facilitating the oxygen reduction kinetics for the robust of methanol synthesis.

ANGPTL4 plays a paradoxical role in gastric cancer through the LGALS7 and Hedgehog pathways.

Gastric cancer (GC) is a malignant disease worldwide. Angiopoietin-like protein 4 (ANGPTL4) plays a role in pathophysiological processes, including metabolic reprogramming, angiogenesis, proliferation, and metastasis. Current evidence shows conflicting findings regarding the role of ANGPTL4 in the progression of GC. ANGPTL4 in GC was confirmed through bioinformatic analysis and immunofluorescence staining. The impact of ANGPTL4 was subsequently validated in GC cell lines using various assays, including 5-ethynyl-2-deoxyuridine (EdU), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow Cytometry (FCM), wound healing, transwell, tube formation, chorioallantoic membrane model, and nude mouse model assays. RNA-seq analysis, polymerase chain reaction (PCR), western blotting (WB), immunofluorescence (IF) and coimmunoprecipitation (co-IP) were conducted to determine the potential downstream mechanism of ANGPTL4. In SNU5 and MKN7 cells, ANGPTL4 was found to augment proliferation, migration, invasion, evasion of apoptosis, and angiogenesis. Conversely, in the AGS cell line, ANGPTL4 was observed to suppress these processes. Notably, the overexpression of ANGPTL4 in AGS cells led to the upregulation of LGALS7, which has emerged as a pivotal factor contributing to the manifestation of an anticancer phenotype induced by ANGPTL4. LGALS7, which is involved in the regulation of the hedgehog pathway and subsequent promotion of GC progression through various processes, such as proliferation, migration, apoptosis evasion, angiogenesis, and lymphangiogenesis, was found to contribute to the contradictory effects of ANGPTL4.

Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND: Currently, there are no reliable methods for predicting and preventing atrial fibrillation (AF) in its early stages. This study aimed to identify plasma proteins associated with AF to discover biomarkers and potential drug targets. METHODS: The UK Biobank Pharma Proteomics Project examined 2923 circulating proteins using the Olink platform, forming the basis of this prospective cohort study. The UK Biobank Pharma Proteomics Project included a randomly selected discovery cohort and the consortium-selected replication cohort. The study's end point was incident AF, identified using International Classification of Diseases, Tenth Revision codes. The association between plasma proteins and incident AF was evaluated using Cox proportional hazard models in both cohorts. Proteins present in both cohorts underwent Mendelian randomization analysis to delineate causal connections, utilizing cis-protein quantitative trait loci as genetic tools. The predictive efficacy of the identified proteins for AF was assessed using the area under the receiver operating characteristic curve, and their druggability was explored. RESULTS: Data from 38 784 participants were included in this study. Incident AF cases were identified in the discovery cohort (1894; 5.5%) within a median follow-up of 14.5 years and in the replication cohort (451; 10.6%) within a median follow-up of 14.4 years. Twenty-one proteins linked to AF were identified in both cohorts. Specifically, COL4A1 (collagen IV α-1; odds ratio, 1.11 [95% CI, 1.04-1.19]; false discovery rate, 0.016) and RET (proto-oncogene tyrosine-protein kinase receptor Ret; odds ratio, 0.96 [95% CI, 0.94-0.98]; false discovery rate, 0.013) demonstrated a causal link with AF, and RET is druggable. COL4A1 improved the short- and long-term predictive performance of established AF models, as evidenced by significant enhancements in the area under the receiver operating characteristic, integrated discrimination improvement, and net reclassification index, all with P values below 0.05. CONCLUSIONS: COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction. Future studies are needed to evaluate the effectiveness of targeting these proteins to reduce AF risk.

Cell cycle checkpoint revolution: targeted therapies in the fight against malignant tumors.

Malignant tumors are among the most important causes of death worldwide. The pathogenesis of a malignant tumor is complex and has not been fully elucidated. Studies have shown that such pathogenesis is related to abnormal cell cycle progression. The expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors as well as functions of the cell cycle checkpoints determine whether the cell cycle progression is smooth. Cell-cycle-targeting drugs have the advantages of high specificity, low toxicity, low side effects, and low drug resistance. Identifying drugs that target the cell cycle and applying them in clinical treatments are expected to promote chemotherapeutic developments against malignant tumors. This article aims to review drugs targeted against the cell cycle and their action mechanisms.

Ibrutinib Promotes Atrial Fibrillation by Disrupting A-Kinase Anchoring Protein 1-Mediated Mitochondrial Quality Surveillance in Cardiomyocytes.

Background: Ibrutinib, a potent Bruton's tyrosine kinase inhibitor with marked efficacy against hematological malignancies, is associated with the heightened risk of atrial fibrillation (AF). Although ibrutinib-induced AF is linked to enhanced oxidative stress, the underlying mechanisms remain unclear. Objective: This research aimed to explore the molecular mechanism and regulatory target in ibrutinib-induced AF. Methods: We performed in vivo electrophysiology studies using ibrutinib-treated mice, and then employed proteomic and single-cell transcriptomic analyses to identify the underlying targets and mechanisms. The effects of A-kinase anchoring protein 1 (AKAP1) depletion on mitochondrial quality surveillance (MQS) were evaluated using both in vivo and ex vivo AKAP1 overexpression models. Results: Atrial AKAP1 expression was significantly reduced in ibrutinib-treated mice, leading to inducible AF, atrial fibrosis, and mitochondrial fragmentation. These pathological changes were effectively mitigated in an overexpression model of ibrutinib-treated mice injected with an adeno-associated virus carrying Akap1. In ibrutinib-treated atrial myocytes, AKAP1 down-regulation promoted dynamin-related protein 1 (DRP1) translocation into mitochondria by facilitating DRP1 dephosphorylation at Ser637, thereby mediating excessive mitochondrial fission. Impaired MQS was also suggested by defective mitochondrial respiration, mitochondrial metabolic reprogramming, and suppressed mitochondrial biogenesis, accompanied by excessive oxidative stress and inflammatory activation. The ibrutinib-mediated MQS disturbance can be markedly improved with the inducible expression of the AKAP1 lentiviral system. Conclusions: Our findings emphasize the key role of AKAP1-mediated MQS disruption in ibrutinib-induced AF, which explains the previously observed reactive oxygen species overproduction. Hence, AKAP1 activation can be employed to prevent and treat ibrutinib-induced AF.

Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of GRP78 in Human Osteosarcoma.

BACKGROUND: Glucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest. OBJECT: This study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78. METHODS: Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)- Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'- deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were analyzed using bioinformatics and electron microscopy. The data were analyzed finally. RESULTS: DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade. CONCLUSION: Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.

From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis.

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host's maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK-STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.

Angiopoietin-4 expression and potential mechanisms in carcinogenesis: Current achievements and perspectives.

As one of the factors regulating tumour angiogenesis, angiopoietin-4 (ANGPT4), which plays an important role in promoting tumour proliferation, survival, expansion and angiogenesis, is highly expressed in some tumours, such as lung adenocarcinoma, glioblastoma and ovarian cancer. This may be related to the fact that ANGPT4 affects the blood vessels and lymphatic system of the tumour. Specifically, ANGPT4 could play an effective role in promoting cancer by affecting the tyrosine kinase receptor TIE2, ERK1/2 and PI3K/AKT signalling pathways. Therefore, ANGPT4 may be an important biomarker for the occurrence and development of cancer and poor prognosis. In addition, the inhibition of ANGPT4 may be a useful cancer treatment. This paper reviews the latest preclinical research on ANGPT4, emphasizes its role in tumourigenesis and broadens our understanding of the carcinogenic function of ANGPT4 and the development of ANGPT4 inhibitors. This is the latest version of the revised version of the previous article.

The role of ESM1 in the lipids metabolic reprogramming and angiogenesis of lung adenocarcinoma cells.

Background: Lung adenocarcinoma (LUAD) is one of the respiratory diseases with high mortality and incidence. As an important angiogenic factor, (Endothelial cell-specific molecule 1) ESM1 plays an important role in the occurrence and development of LUAD. However, the role and molecular mechanism of ESM1 on LUAD metabolic reprogramming and angiogenesis remain unclear. Methods: We used multiple databases to analyze the prognostic significance and potential function of ESM1 in patients with LUAD. The expression of ESM1 in LUAD cells was down-regulated/overexpressed by RNA interference, and the effects of ESM1 on the proliferation, migration, lipid metabolism and angiogenesis of LUAD cells in vitro and in vivo were analyzed using MTT, EdU, wound healing, oil red O, tubule formation, xenograft tumor model and chicken embryo allantoic model. Results: ESM1 is closely associated with poor prognosis in LUAD patients. ESM1 promotes LUAD proliferation, migration, fatty acid synthesis and angiogenesis. It also accelerates the proliferation, migration, lipid synthesis and tubule formation of endothelial cells in the tumor microenvironment in the form of secreted protein. Mechanically, ESM1 can promote the activation of AKT signaling pathway and up-regulate the expression of SCD1 and FASN. Conclusion: Our results suggest that ESM1 promotes the proliferation, migration, lipid reprogramming, and angiogenesis of LUAD cells by activating the AKT signaling pathway, suggesting that ESM1 may be a potential therapeutic target and prognostic marker in LUAD patients.

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

The association of weight-adjusted waist index with the risk of osteoporosis in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: The relationship between obesity and type 2 diabetes with bone health has always been a topic of debate. The weight-adjusted waist index has become a commonly used indicator for assessing central obesity, fat, and muscle mass. However, currently there is no research reporting the association between weight-adjusted waist index and risk of osteoporosis in populations of type 2 diabetes. Therefore, this study aims to provide new information on the association between weight-adjusted waist index and risk of osteoporosis in type 2 diabetes. METHODS: This cross-sectional study involved 963 patients with type 2 diabetes who were admitted to the Department of Endocrinology of Cangzhou Central Hospital. Multivariate logistic regression models were used to assess the association between weight-adjusted waist index and osteoporosis. The potential nonlinear association was evaluated. The effects of interaction between subgroups were assessed using the likelihood ratio test. RESULTS: Weight-adjusted waist index was positively associated with the risk of osteoporosis, regardless of traditional confounding factors. For each 1 unit increased in weight-adjusted waist index, the risk of osteoporosis increased by 67%. Furthermore, there was a nonlinear relationship between weight-adjusted waist index and osteoporosis. The subgroup analysis did not reveal any significant interactions. CONCLUSIONS: Our study indicated a positive association between weight-adjusted waist index and the risk of osteoporosis in adult Chinese type 2 diabetes patients, and this relationship was nonlinear.

Comprehensive Engineering Strategies for Heterologous Production of Zealexin A1 in Saccharomyces cerevisiae.

Zealexin A1 is a nonvolatile sesquiterpene phytoalexin, which not only exhibits extensive antifungal and insecticidal activities but also has the ability to enhance the drought resistance of plants, and thus has potential applications in agricultural and food fields. In this study, the biosynthetic pathway of zealexin A1 was constructed in Saccharomyces cerevisiae for the first time, and the highest production of zealexin A1 reported to date was achieved. First, through screening of sesquiterpene synthases from various plants, BdMAS11 had a stronger (S)-ß-macrocarpene synthesis ability was obtained, and the heterologous synthesis of zealexin A1 was achieved by coexpressing BdMAS11 with cytochrome P450 oxygenase ZmCYP71Z18. Subsequently, after the site-directed mutagenesis of BdMAS11, fusion expression of farnesyl diphosphate synthase ERG20 and BdMAS11, and tailored truncation of BdMAS11 and ZmCYP71Z18, the strain coexpressing the manipulated BdMAS11 and original ZmCYP71Z18 produced 119.31 mg/L of zealexin A1 in shake-flask fermentation. Finally, the production of zealexin A1 reached 1.17 g/L through fed-batch fermentation in a 5 L bioreactor, which was 261.7-fold that of the original strain. This study lays the foundation for the industrial production of zealexin A1 and other terpenoids.

Sex Differences in 'Life's Essential 8' cardiovascular health and Type 2 Diabetes Mellitus Risk Across Menopause Stages.

AIM: The purpose of this paper is to explore sex-based differences in cardiovascular health (CVH) and the incidence of type 2 diabetes mellitus (T2DM) among women at different menopausal stages and men. METHODS: A prospective cohort study was conducted, involving 126,818 participants without pre-existing T2DM from the UK Biobank. CVH was assessed using the Life's Essential 8. Absolute risks (ARs) and hazard ratios (HRs) were separately employed to assess the association between increased CVH and T2DM risk. The Accelerated Failure Time model assessed the impact of CVH on the time to T2DM onset. RESULTS: Over a mean follow-up of 168 months, 4,315 cases of T2DM were documented. In men, each one-point increase in CVH was associated with a 0.268% decrease in AR and a 6.4% decrease in HR for T2DM. In premenopausal, perimenopausal and postmenopausal women, each unit increase in CVH resulted in a 0.105%, 0.180% and 0.166% decrease in AR and a 7.7%, 5.2% and 6.4% decrease in HR of T2DM. The adjusted median time to T2DM onset was delayed by 12.46, 9.83, 11.5 and 21.43 months in the highest quintile of men, premenopausal, perimenopausal and postmenopausal women, respectively, compared with the lowest CVH quintile. CONCLUSIONS: As CVH improved, the reduction in AR for T2DM was more prominent in men than in women. HR trends for CVH and T2DM were similar in men and postmenopausal women. Increased CVH delayed the onset of T2MD in both men and women, with the most significant delay observed in postmenopausal women.

ZnIn2Se4 nanoparticles photocatalyst for efficient solar fuel production.

Selecting a suitable photocatalyst to establish the Z-scheme heterojunction which is accompanied by effective photogenerated hole and electron separation, is one of the advantageous strategies for efficient photocatalytic solar energy conversion. Therefore, we prepared a ZnIn2Se4 nanoparticles photocatalyst to build a double Z-scheme heterojunction with mixed-phase TiO2 nanofibers, boosting photocatalytic solar fuel preparation. The result of X-ray photoelectron spectroscopy confirmed the existence of interfacial chemical bonds and internal electric fields. The interfacial Ti-Se bond is regarded as a channel and the internal electric field serves as the driving force for electron transfer. And the composite photocatalyst exhibits a great hydrogen evolution rate of 0.11 mmol g-1 h-1. From a forward-working perspective, this work proposes a ZnIn2Se4 nanoparticles photocatalyst for efficient solar fuel conversion, promoting the application of bimetallic selenide photocatalyst in the field of photocatalysis.

Manipulation of Multimodal and Multicolor Luminescence via Interplay of Traps and Rare Earth Emission Centers in Calcium Tungstate.

Multimodal luminescence involves color-tunable and wavelength manageable photon emissions upon variable luminescence pathways in response to different external stimuli, which provides clear visualization and high-level confidentiality for information encryption technologies. Integrating multimodal luminescence into a single matrix is regarded as a feasible strategy but remains a big challenge. In this work, multimodal (photoluminescence, persistent luminescence, upconversion luminescence, and thermally stimulated luminescence) and multicolor luminescence (green, yellow, orange, pink to red) is achieved in CaWO4:Yb3+,Er3+,Eu3+ phosphor by employing an interplay of traps and rare earth emission centers. Bright emission in a wide color gamut is achieved dynamically in response to thermal disturbance and light illumination, which further allows for on-demand emission manipulation in space and time dimensions. The compatible coexistence of multiple rare earth emissive centers together with abundant photoactive traps contributes to the excellent integration of multimodal photon emissions in calcium tungstate. This work provides a good example of integrating multimodal luminescence into one single matrix and indicates potential in advanced high-level information encryption applications.

Development of starch-cellulose composite films with antimicrobial potential.

This study explored the structure and performance of starch-based antibacterial films reinforced with black tea cellulose nanocrystals (BT-CNCs). The optimal addition amount of BT-CNCs is 5 % (w/w Starch). This nanocrystal-infused film, incorporating chitosan (CS), ε-polylysine (ε-PL), and zinc oxide nanoparticles (ZnONP) as antibacterial agents, exhibited a smooth, continuous surface. The addition of BT-CNCs and antibacterial agents did not change the group characteristic peaks of the film, but changed the crystallinity slightly. The films, namely St, St/CNCs, St/CNCs/CS, and St/CNCs/ε-P, maintained high light transmittance (above 80 %), except for the St/CNCs/ZnONP film, which effectively shielded UV radiation. The combined use of antibacterial agents and BT-CNCs enhanced the water and oxygen barrier properties of the film. Notably, the St/CNCs/CS film exhibited the lowest solubility (17.74 % ± 0.36) and the highest tensile strength (14.23 ± 0.16 MPa). The antibacterial efficacy of the films decreased in the order of St/CNCs/ZnONP, St/CNCs/ε-PL, and St/CNCs/CS, with a more pronounced inhibitory effect on E. coli compared to S. aureus. This study marries natural waste recycling with cutting-edge food packaging technology, setting a new benchmark for the development of sustainable packaging materials.

Liraglutide reduces bone marrow adipogenesis by miR-150-5p/ GDF11 axis in diabetic rats.

In recent years, a common-used antidiabetic drug, liraglutide, was identified with extra effects on lipid metabolism. Its effects against excessive lipid deposition in bone marrow were gained much attention but not well established. Our aim in the present study is to explore the interaction of miRNAs-mRNAs altered by liraglutide administration during bone marrow adipogenesis in diabetes. To establish the diabetic animal model, rats were treated with high fat diet (HFD) and STZ injection. We then identified the lowering effect of liraglutide on lipids metabolism in the diabetes. During this process, high-throughput sequencing and bioinformatics analyses on miRNAs extracted from bone marrow mesenchymal stem cells (BMSCs) were conducted after liraglutide administration. We then identified five differentially expressed miRNAs (miRNA-150-5p, miRNA-129-5p, miRNA-201-3p, miRNA-201-5p, and miRNA-214-5p). The expressions of the DE miRNAs were verified as temporal specific expression patterns in Day 3 and in Day 7. Among them, miRNA-150-5p expression was more stable and consistent with the sequencing data. Of interest, miR-150-5p overexpression facilitated adipogenesis of BMSCs. But this promotion was alleviated by liraglutide. The predicted target gene of miR-150-5p, GDF11, was validated to be involved in liraglutide alleviated BMSCs' lipid accumulation in diabetes. In vitro, liraglutide increased the GDF11 expression, rescued its down-expression by siGDF11 and inhibit the adipogenesis of BMSCs cultured in high glucose medium. In vivo, liraglutide reversed the HFD-STZ induced excessive lipid droplets by up-regulation of GDF11 expression, which was discounted by agomiR-150-5p injection. Above all, liraglutide might alleviate bone marrow fat accumulation via inactivating miR-150-5p/GDF11 axis in diabetes.

A Universal Electronic Structure Modulation Strategy: Is Strong Adsorption Always Correlated with High Catalysis?

Unveiling the inherent link between polysulfide adsorption and catalytic activity is key to achieving optimal performance in Lithium-sulfur (Li-S) batteries. Current research on the sulfur reaction process mainly relies on the strong adsorption of catalysts to confine lithium polysulfides (LiPSs) to the cathode side, effectively suppressing the shuttle effect of polysulfides. However, is strong adsorption always correlated with high catalysis? The inherent relationship between adsorption and catalytic activity remains unclear, limiting the in-depth exploration and rational design of catalysts. Herein, the correlation between "d-band center-adsorption strength-catalytic activity" in porous carbon nanofiber catalysts embedded with different transition metals (M-PCNF-3, M = Fe, Co, Ni, Cu) is systematically investigated, combining the d-band center theory and the Sabatier principle. Theoretical calculations and experimental analysis results indicate that Co-PCNF-3 electrocatalyst with appropriate d-band center positions exhibits moderate adsorption capability and the highest catalytic conversion activity for LiPSs, validating the Sabatier relationship in Li-S battery electrocatalysts. These findings provide indispensable guidelines for the rational design of more durable cathode catalysts for Li-S batteries.

MUC21: a new target for tumor treatment.

MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a transmembrane domain and a cytoplasmic tail. MUC21 is expressed is observed in normal tissues in organs like the thymus, testes, lungs, and large intestine. Research has shown that MUC21 is expressed in esophageal squamous cell carcinoma, lung adenocarcinoma, glioblastoma, thyroid cancer, melanoma, and various other malignant tumors in distinctive manner. Additionally, tumor invasion, metastasis, and poor prognosis are linked to it. Some researchers believe that MUC21 has the potential to become a new target in cancer treatment. This review aims to deliver a comprehensive overview of the glycosylation, function, and research progress of MUC21 in multiple types of cancer and infectious diseases.