Fabrication of injectable alginate hydrogels with sustained release of 4-octyl itaconate for articular anti-inflammatory.

BACKGROUND: Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE: The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS: In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS: After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 µM 4-OI effectively significantly reduced the expression of TNF-α, IL-1ß, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION: 4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.

[Action mechanism of Huotu Jiji Pellets in the treatment of erectile dysfunction: An exploration based on network pharmacology and molecular docking].

OBJECTIVE: To explore the potential action mechanism of Huotu Jiji Pellets (HJP) in the treatment of erectile dysfunction (ED) based on network pharmacology and molecular docking. METHODS: We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine (TCMIP) and the therapeutic target genes of ED from the databases of Genecards. Then we obtained the common targets of HJP and ED using the Venny software, constructed a protein-protein interaction (PPI) network of HJP acting on ED, and screened out the core targets with the Cytoscape software. Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software. RESULTS: A total of 64 effective compounds, 822 drug-related targets, 1 783 disease-related targets and 320 common targets were obtained in this study. PPI network analysis showed that the core targets of HJP for ED included ESR1, HSP90AA1, SRC, and STAT3. GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus, positive regulation of kinase activity, and positive regulation of MAPK cascade. KEGG pathway enrichment analysis suggested that PI3K-Akt, apoptosis, MAPK, HIF-1, VEGF, autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED. Molecular docking prediction exhibited a good docking activity of the key active molecules of HJP with the core targets. CONCLUSION: This study showed that HJP acted on ED through multi-components, multi-targets and multi-pathways, which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Small extracellular vesicle CA1 as a promising diagnostic biomarker for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.

Metal-Organic Framework with Space-Partition Pores by Fluorinated Anions for Benchmark C2H2/CO2 Separation.

The efficient separation of C2H2 from C2H2/CO2 or C2H2/CO2/CH4 mixtures is crucial for achieving high-purity C2H2 (>99%), essential in producing contemporary commodity chemicals. In this report, we present ZNU-12, a metal-organic framework with space-partitioned pores formed by inorganic fluorinated anions, for highly efficient C2H2/CO2 and C2H2/CO2/CH4 separation. The framework, partitioned by fluorinated SiF62- anions into three distinct cages, enables both a high C2H2 capacity (176.5 cm3/g at 298 K and 1.0 bar) and outstanding C2H2 selectivity over CO2 (13.4) and CH4 (233.5) simultaneously. Notably, we achieve a record-high C2H2 productivity (132.7, 105.9, 98.8, and 80.0 L/kg with 99.5% purity) from C2H2/CO2 (v/v = 50/50) and C2H2/CO2/CH4 (v/v = 1/1/1, 1/1/2, or 1/1/8) mixtures through a cycle of adsorption-desorption breakthrough experiments with high recovery rates. Theoretical calculations suggest the presence of potent "2 + 2" collaborative hydrogen bonds between C2H2 and two hexafluorosilicate (SiF62-) anions in the confined cavities.

A novel hydrophobic carborane-hybrid microporous material for reversed C2H6 adsorption and efficient C2H4/C2H6 separation under humid conditions.

Since ethylene (C2H4) is important feedstock in the chemical industry, developing economical and energy-efficient adsorption separation techniques based on ethane (C2H6)-selective adsorbents to replace the energy-intensive cryogenic distillation is highly demanded, which however remains a daunting challenge. While previous anionic boron cluster hybrid microporous materials display C2H4-selective features, we herein reported that the incorporation of a neutral para-carborane backbone and aliphatic 1,4-diazabicyclo[2.2.2]octane (DABCO) enables the reversed adsorption of C2H6 over C2H4. The generated carborane-hybrid microporous material ZNU-10 (ZNU = Zhejiang Normal University) is highly stable in humid air and maintains good C2H6/C2H4 separation performance under high humidity. Gas loaded single crystal structure and density-functional theory (DFT) calculations revealed that the weakly polarized carborane and DABCO within ZNU-10 induce more specific C-Hδ+⋯Hδ--B dihydrogen bonds and other van der Waals interactions with C2H6, while the suitable pore space allows the high C2H6 uptake. Approximately 14.5 L kg-1 of polymer grade C2H4 can be produced from simulated C2H6/C2H4 (v/v 10/90) mixtures under ambient conditions in a single step, comparable to those of many popular materials.

Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein-Barr virus entry into epithelial cells.

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.

MicroRNA 98-5p Overexpression Contributes to Delayed Fracture Healing via Targeting BMP-2.

MicroRNAs (miRNAs) are related to the regulation of bone metabolism. Delayed fracture healing (DFH) is a common complication after fracture surgery. The study attempted to examine the role of miR-98-5p and bone morphogenetic protein (BMP)-2 with the onset of DFH. A total of 140 patients with femoral neck fracture were recruited, including 80 cases with normal fracture healing (NFH) and 60 cases with DFH. MC3T3-E1 cells were induced cell differentiation for cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to test mRNA levels. Cell proliferation and apoptosis were determined via CCK-8 and flow cytometry assay. Luciferase reporter assay was done to verify the targeted regulatory relationship of miR-98-5p with BMP-2. In comparison with NFH cases, DFH patients owned high levels of serum miR-98-5p and low concentration of BMP-2, and the levels of the two indexes are significantly negatively correlated. Both miR-98-5p and BMP-2 had the ability to predict DFH, while their combined diagnostic value is the highest. BMP-2 was demonstrated to be the target gene of miR-98-5p. Overexpression of BMP-2 reversed the role of miR-98-5p in MC3T3-E1 cell proliferation, apoptosis and differentiation. Increased miR-98-5p and decreased BMP-2 serve as potential biomarkers for the diagnosis of DFH. MiR-98-5p overexpression inhibits osteoblast proliferation and differentiation via targeting BMP-2.

Specific Propyne Trapping Sites within a Robust MOF for Efficient Propyne/Propadiene Separation with Record Propadiene Productivity.

Separating propyne/propadiene to produce pure propadiene is extremely challenging in industry due to their similar properties. Herein, a novel ZrF6 2- anion pillared cage-like metal-organic framework (termed as CuZrF6 -TPA) for highly efficient propyne/propadiene separation is reported. It exhibits high propyne capacity (177.4/188.6 cm3 /cm3 at 0.5/1.0 bar and 298 K), benchmark separation selectivity (6.0), and remarkable separation potential (5.7 mol L-1 ) simultaneously. Record propadiene productivity (≈4.7 mol L-1 ) is achieved through a single adsorption process in breakthrough experiments with excellent recycle stability even under humid conditions. Based on the structure of propyne-loaded single crystals, two binding sites are identified, including a major propyne trapping site at the windows and a minor binding site located in the large cages. Modelling studies further confirm that the contracted cage windows surrounded with rotating Lewis basic F atoms and aromatic rings are the optimal bonding sites to capture propyne with multiple hydrogen bonding and π···π interactions.

A study on molecular mechanism of Xihuang pill in the treatment of glioblastoma based on network pharmacology and validation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. AIM OF THE STUDY: This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. RESULTS: A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1ß, INF-γ was increased and the production of IL-10, TGF-ß1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. CONCLUSION: Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma.

EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma.

This study aimed to develop a model using Epstein-Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis. These 25 genes were used to classify NPC into two subtypes, and six genes (C16orf54, CD27, CD53, CRIP1, RARRES3, and TBC1D10C) were found to be hub genes in NPC related to immune infiltration and cell cycle regulation. It was shown that these genes could be used to predict the prognosis of NPC, with functions related to tumor proliferation and immune infiltration, making them potential therapeutic targets. The findings of this study could aid in the development of screening and prognostic methods for NPC based on EBV-related features.

Topological Design of Unprecedented Metal-Organic Frameworks Featuring Multiple Anion Functionalities and Hierarchical Porosity for Benchmark Acetylene Separation.

Separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) or ethylene (C2 H4 ) is industrially important but still challenging so far. Herein, we developed two novel robust metal organic frameworks AlFSIX-Cu-TPBDA (ZNU-8) with znv topology and SIFSIX-Cu-TPBDA (ZNU-9) with wly topology for efficient capture of C2 H2 from CO2 and C2 H4 . Both ZNU-8 and ZNU-9 feature multiple anion functionalities and hierarchical porosity. Notably, ZNU-9 with more anionic binding sites and three distinct cages displays both an extremely large C2 H2 capacity (7.94 mmol/g) and a high C2 H2 /CO2 (10.3) or C2 H2 /C2 H4 (11.6) selectivity. The calculated capacity of C2 H2 per anion (4.94 mol/mol at 1 bar) is the highest among all the anion pillared metal organic frameworks. Theoretical calculation indicated that the strong cooperative hydrogen bonds exist between acetylene and the pillared SiF6 2- anions in the confined cavity, which is further confirmed by in situ IR spectra. The practical separation performance was explicitly demonstrated by dynamic breakthrough experiments with equimolar C2 H2 /CO2 mixtures and 1/99 C2 H2 /C2 H4 mixtures under various conditions with excellent recyclability and benchmark productivity of pure C2 H2 (5.13 mmol/g) or C2 H4 (48.57 mmol/g).

Ultra-weak photon emission as a potential tool for evaluating the therapeutic effect of traditional Chinese medicine in patients with type 2 diabetes.

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

Highly Efficient CO2/C2H2 Separation by Porous Graphene via Quadrupole Gating Mechanism.

Acetylene (C2H2) is an important and widely used raw material in various industries (such as petrochemical). Generally, a product yield is proportional to the purity of C2H2; however, C2H2 from a typical industrial gas-production process is commonly contaminated by CO2. So far, the achievement of high-purity C2H2 separated from a CO2/C2H2 mixture is still challenging due to their very close molecular dimensions and boiling temperatures. Taking advantage of their quadrupoles with opposite signs, here, we show that the graphene membrane embedded with crown ether nanopores can achieve an unprecedented separation efficiency of CO2/C2H2. Combining the molecular dynamics simulation and the density functional theory (DFT) approaches, we discovered that the electrostatic gas-pore interaction favorably allows the fast transport of CO2 through crown ether nanopores while completely prohibiting C2H2 transport, which yields a remarkable permeation selectivity. In particular, the utilized crown ether pore is capable of allowing the individual transport of CO2 while completely rejecting the passage of C2H2, independent of the applied pressures, fed gases ratios, and exerted temperatures, featuring the superiority and robustness of the crown pore in CO2/C2H2 separation. Further, DFT and PMF calculations demonstrate that the transport of CO2 through the crown pore is energetically more favorable than the transport of C2H2. Our findings reveal the potential application of graphene crown pore for CO2 separation with outstanding performance.

Rapid Adaptation of Chimonobambusa opienensis Leaves to Crown-Thinning in Giant Panda Ecological Corridor, Niba Mountain.

Leaf traits reflect the ecological strategy in heterogeneous contexts and are widely used to explore the adaption of plant species to environmental change. However, the knowledge of short-term effect of canopy management on understorey plant leaf traits is still limited. Here, we studied the short-term effect of crown-thinning on the leaf morphological traits of bamboo (Chimonobambusa opienensis), an important understorey plant and staple food for the giant panda (Ailuropoda melanoleuca) of Niba Mountain. Our treatments were two crown-thinnings (spruce plantation, CS, and deciduous broad-leaved forest, CB) and two controls (broad-leaved forest canopy, FC, and the bamboo grove of clearcutting, BC). The results showed that: the CS enhanced the annual leaf length, width, area, and thickness, CB decreased almost all annual leaf traits, and perennial leaf traits in CS and CB were the opposite. The log-transformed allometric relationships of length vs. width, biomass vs. area were significantly positive while those of specific leaf area vs. thickness were significantly negative, which varied largely in treatments and age. The leaf traits and allometric relationships suggested that the CS created a more suitable habitat for bamboo growth. This study highlighted that the understorey bamboo leaf traits could adapt the improved light environment induced by crown-thinning rapidly.

Targeting exosomes enveloped EBV-miR-BART1-5p-antagomiRs for NPC therapy through both anti-vasculogenic mimicry and anti-angiogenesis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with high incidence in China. The molecular mechanisms of vasculogenic mimicry (VM) and angiogenesis are not fully elucidated in NPC. More specially, it has seldomly been reported that Epstein-Barr virus-encoded miRNA can regulate VM and angiogenesis in NPC. The aim of this study was to investigate the function and molecular mechanism of a targeting exosome system (iRGD-exo-antagomiR) against VM and angiogenesis in NPC, and to provide new approaches for improving the comprehensive treatment of NPC. METHODS: Exosomes were isolated by differential ultracentrifugation. Dynamic light scattering, transmission electron microscopy and western blotting were performed to characterize the exosomes. The 3D-Culture assay, tube formation assay, chicken chorioallantoic membrane assay, Matrigel plug assay, mouse xenograft tumor modeling and immunohistochemical staining were applied to evaluate the anti-VM and anti-angiogenic effects of the targeting exosome system in vitro and in vivo. Western blot was performed to detect the changes of downstream regulated networks following interference and recovery of the target gene. RESULTS: In vitro or in vivo treatment with iRGD-tagged exosome containing antagomiR-BART1-5p specifically suppressed VM and angiogenesis in NPC. EBV-miR-BART1-5p promoted VM and angiogenesis in vitro and in vivo by regulating VEGF, PI3K, Akt, mTOR and HIF1-α in a Spry2-dependent manner. CONCLUSIONS: Our findings demonstrated that targeting exosomes enveloped EBV-miR-BART1-5p-antagomiRs in a Spry2-dependent manner for NPC therapy through both anti-VM and anti-angiogenesis in vitro and in vivo.

Study on the Mechanism of Burr Formation by Simulation and Experiment in Ultrasonic Vibration-Assisted Micromilling.

Due to the strong plasticity of Inconel 718 and the significant size effect of micromachining, a large number of burrs will be produced in traditional processing. The addition of ultrasonic vibration during machining can reduce the burr problem. The mechanism of burr generation in traditional micromilling (TMM) and ultrasonic vibration-assisted micromilling (UVAMM) was analyzed by simulation, and verified by corresponding experiments. It is found that applying high-frequency ultrasonic vibration in the milling feed direction can reduce cutting temperature and cutting force, improve chip breaking ability, and reduce burr formation. When the cutting thickness will reach the minimum cutting thickness hmin, the chip will start to form. When A/ƒz > 1/2, the tracks of the two tool heads start to cut, and the chips are not continuous. Some of the best burr suppression effects were achieved under conditions of low cutting speed (Vc), feed per tooth (ƒz), and large amplitude (A). When A is 6 µm, the size and quantity of burr is the smallest. When ƒz reaches 6 µm, large continuous burrs appear at the top of the groove. The experimental results further confirm the accuracy of the simulation results and provide parameter reference.

Metformin alleviates ethanol-induced cardiomyocyte injury by activating AKT/Nrf2 signaling in an ErbB2-dependent manner.

BACKGROUND: Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were exposed to ethanol for 24 h to establish an ethanol-induced cardiomyocyte injury model, and followed by treatment with metformin in the presence or absence of Lapatinib (an ErbB2 inhibition). CCK8 and LDH assays demonstrated that metformin improved cell viability in cardiomyocytes exposed to ethanol. Furthermore, metformin suppressed cardiomyocyte apoptosis and reduced the expressions of apoptosis-related proteins (Bax and C-CAS-3). In addition, our results showed that metformin activated the AKT/Nrf2 pathway, and then promoted Nrf2 nuclear translocation and the transcription of its downstream antioxidant genes (HO-1, CAT and SOD2), thereby inhibiting oxidative stress. Interestingly, we found that ErbB2 protein expression was significantly inhibited in ethanol-treated cardiomyocytes, which was markedly reversed by metformin. In contrast, Lapatinib largely abrogated the activation of AKT/Nrf2 signaling by metformin, accompanied by the increases in oxidative stress and cardiomyocyte apoptosis, indicating that metformin prevented ethanol-induced cardiomyocyte injury in an ErbB2-dependent manner. CONCLUSION: In summary, our study provides the first evidence that metformin protects cardiomyocyte against ethanol-induced oxidative stress and apoptosis by activating ErbB2-mediated AKT/Nrf2 signaling. Thus, metformin may be a potential novel treatment approach for alcoholic cardiomyopathy.

Authentication of Asini Corii Colla and Taurus Corii Colla based on UPLC-MS/MS and the discovery of antioxidant peptides associated with the PI3K-AKT pathway.

Asini Corii Colla (ACC) and Taurus Corii Colla (TCC) are well-known for their high nutritional value, especially for medicinal purposes. However, the aforementioned are also potential candidates for adulteration because of their low yield and high price. A UPLC-MS/MS approach based on the specific peptide was proposed to detect adulterated gelatin with possible mixed animal species. To explore the antioxidant activity, the peptides were separated to evaluate their effect on ·OH radical and DPPH· scavenging activity, together with PI3K-AKT pathway activation. The results showed that the peptides had excellent DPPH· and ·OH radical scavenging effects, and could alleviate H2O2-induced oxidative stress by promoting the phosphorylation of PI3K and AKT. According to the results of MALDI-TOF/MS, the shared mass-to-charge ratio (m/z) 1466, 1744 and 2382 may serve as a material basis for the antioxidant activity of both ACC and TCC, and contribute to their traditional tonic effects.

Insights into the thermodynamic-kinetic synergistic separation of propyne/propylene in anion pillared cage MOFs with entropy-enthalpy balanced adsorption sites.

Propyne/propylene (C3H4/C3H6) separation is an important industrial process yet challenged by the trade-off of selectivity and capacity due to the molecular similarity. Herein, record C3H4/C3H6 separation performance is achieved by fine tuning the pore structure in anion pillared MOFs. SIFSIX-Cu-TPA (ZNU-2-Si) displays a benchmark C3H4 capacity (106/188 cm3 g-1 at 0.01/1 bar and 298 K), excellent C3H4/C3H6 IAST selectivity (14.6-19.3) and kinetic selectivity, and record high C3H4/C3H6 (10/90) separation potential (36.2 mol kg-1). The practical C3H4/C3H6 separation performance is fully demonstrated by breakthroughs under various conditions. 37.8 and 52.9 mol kg-1 of polymer grade C3H6 can be produced from 10/90 and 1/99 C3H4/C3H6 mixtures. 4.7 mol kg-1 of >99% purity C3H4 can be recovered by a stepped desorption process. Based on the in situ single crystal analysis and DFT calculation, an unprecedented entropy-enthalpy balanced adsorption pathway is discovered. MD simulation further confirmed the thermodynamic-kinetic synergistic separation of C3H4/C3H6 in ZNU-2-Si.

Benchmark single-step ethylene purification from ternary mixtures by a customized fluorinated anion-embedded MOF.

Ethylene (C2H4) purification from multi-component mixtures by physical adsorption is a great challenge in the chemical industry. Herein, we report a GeF62- anion embedded MOF (ZNU-6) with customized pore structure and pore chemistry for benchmark one-step C2H4 recovery from C2H2 and CO2. ZNU-6 exhibits significantly high C2H2 (1.53 mmol/g) and CO2 (1.46 mmol/g) capacity at 0.01 bar. Record high C2H4 productivity is achieved from C2H2/CO2/C2H4 mixtures in a single adsorption process under various conditions. The separation performance is retained over multiple cycles and under humid conditions. The potential gas binding sites are investigated by density functional theory (DFT) calculations, which suggest that C2H2 and CO2 are preferably adsorbed in the interlaced narrow channel with high aff0inity. In-situ single crystal structures with the dose of C2H2, CO2 or C2H4 further reveal the realistic host-guest interactions. Notably, rare C2H2 clusters are formed in the narrow channel while two distinct CO2 adsorption locations are observed in the narrow channel and the large cavity with a ratio of 1:2, which accurately account for the distinct adsorption heat curves.