Compressive strain in Cu catalysts: Enhancing generation of C2+ products in electrochemical CO2 reduction.

Elastic strain in Cu catalysts enhances their selectivity for the electrochemical CO2 reduction reaction (eCO2RR), particularly toward the formation of multicarbon (C2+) products. However, the reasons for this selectivity and the effect of catalyst precursors have not yet been clarified. Hence, we employed a redox strategy to induce strain on the surface of Cu nanocrystals. Oxidative transformation was employed to convert Cu nanocrystals to CuxO nanocrystals; these were subsequently electrochemically reduced to form Cu catalysts, while maintaining their compressive strain. Using a flow cell configuration, a current density of 1 A/cm2 and Faradaic efficiency exceeding 80% were realized for the C2+ products. The selectivity ratio of C2+/C1 was also remarkable at 9.9, surpassing that observed for the Cu catalyst under tensile strain by approximately 7.6 times. In-situ Raman and infrared spectroscopy revealed a decrease in the coverage of K+ ion-hydrated water (K·H2O) on the compressively strained Cu catalysts, consistent with molecular dynamics simulations and density functional theory calculations. Finite element method simulations confirmed that reducing the coverage of coordinated K·H2O water increased the probability of intermediate reactants interacting with the surface, thereby promoting efficient C-C coupling and enhancing the yield of C2+ products. These findings provide valuable insights into targeted design strategies for Cu catalysts used in the eCO2RR.

Platelet and red cell responses to three North American pit vipers.

We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell activity, we found differential effects of these venoms on these cellular components. Platelet aggregation was most induced by C. adamanteus. Platelet activation was highest with C. atrox. Red blood cells had calcium expression and erythrocyte formation most induced by C. adamanteus and A. piscivorus. These results demonstrate the complex interplay of individual cellular effects with clinical presentations seen in envenomings from these species.

TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

TMEM16F (also known as ANO6), a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes, such as blood coagulation, neurodegeneration, cell-cell fusion and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight the role of intracellular signaling by TMEM16F in endothelial cells but also open new avenues for exploring the regulatory mechanisms for membrane lipid asymmetry and their implications in disease pathogenesis.

Energy Metabolism: From Physiological Changes to Targets in Sepsis-induced Cardiomyopathy.

Sepsis is a systemic inflammatory response syndrome caused by a variety of dysregulated responses to host infection with life-threatening multi-organ dysfunction. Among the injuries or dysfunctions involved in the course of sepsis, cardiac injury and dysfunction often occur and are associated with the pathogenesis of hemodynamic disturbances, also defined as sepsis-induced cardiomyopathy (SIC). The process of myocardial metabolism is tightly regulated and adapts to various cardiac output demands. The heart is a metabolically flexible organ capable of utilizing all classes of energy substrates, including carbohydrates, lipids, amino acids, and ketone bodies to produce ATP. The demand of cardiac cells for energy metabolism changes substantially in septic cardiomyopathy with distinct etiological causes and different times. This review describes changes in cardiomyocyte energy metabolism under normal physiological conditions and some features of myocardial energy metabolism in septic cardiomyopathy, and briefly outlines the role of the mitochondria as a center of energy metabolism in the septic myocardium, revealing that changes in energy metabolism can serve as a potential future therapy for infectious cardiomyopathy.

Niclosamide potentiates TMEM16A and induces vasoconstriction.

The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease (COPD) but was recently found to possess broad-spectrum off-target effects. Here, we show that, under physiological Ca2+ (200-500 nM) and voltages, niclosamide acutely potentiates TMEM16A. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering clinical applications of niclosamide as a TMEM16A inhibitor. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation and provides insights into developing specific TMEM16A modulators to treat human diseases.

Multi-Scale Analysis of the Damage Evolution of Coal Gangue Coarse Aggregate Concrete after Freeze-Thaw Cycle Based on CT Technology.

This study utilized X-ray computed tomography (CT) technology to analyze the meso-structure of concrete at different replacement rates, using a coal gangue coarse aggregate, after experiencing various freeze-thaw cycles (F-Ts). A predictive model for the degradation of the elastic modulus of Coal Gangue coarse aggregate Concrete (CGC), based on mesoscopic damage, was established to provide an interpretation of the macroscopic mechanical behavior of CGC after F-Ts damage at a mesoscopic scale. It was found that after F-Ts, the compressive strength of concrete, with coal gangue replacement rates of 30%, 60%, and 100%, respectively, decreased by 33.76%, 34.89%, and 42.05% compared with unfrozen specimens. The results indicate that an increase in the coal gangue replacement rate exacerbates the degradation of concrete performance during the F-Ts process. Furthermore, the established predictive formula for elastic modulus degradation closely matches the experimental data, offering a reliable theoretical basis for the durability design of CGC in F-Ts environments.

Giant dielectric response and relaxation behavior of Bi3+/W6+ co-doped TiO2 ceramics.

With the rapid development of electronic information technology, dielectric ceramics are widely used in the field of passive devices such as multi-layer ceramic capacitors. In this paper, (Bi2/3W1/3)xTi1-xO2 (BWTOx) ceramics with superior dielectric properties have been prepared by using a traditional solid-state method. Remarkably, at a (Bi2/3W1/3)4+ doping level of 0.01, a (Bi2/3W1/3)0.01Ti0.99O2 ceramic achieved a giant dielectric permittivity of ∼1.5 × 104 and a low loss tangent of ∼0.07 at 1 kHz, as well as a good temperature independence, which could satisfy the operating temperature standards for X9R capacitors. The abnormal dielectric relaxation in the low temperature region can be explained by the interface polarization. Data based on the complex impedance spectroscopy and X-ray photoemission spectroscopy results indicate that the colossal permittivity of BWTOx ceramics is mainly ascribed to the internal barrier layer capacitance effect. The findings of this work could provide valuable insights for achieving large dielectric constants and good temperature stability simultaneously in BWTOx and other related electronic ceramic materials.

Giant Deformation Induced Staggered-Layer Structure Promoting the Thermoelectric and Mechanical Performance in n-Type Bi2(Te, Se)3.

Bismuth telluride has long been recognized as the most promising near-room temperature thermoelectric material for commercial application; however, the thermoelectric performance for n-type Bi2(Te, Se)3-based alloys is far lagging behind that of its p-type counterpart. In this work, a giant hot deformation (GD) process is implemented in an optimized Bi2Te2.694Se0.3I0.006+3 wt%K2Bi8Se13 precursor and generates a unique staggered-layer structure. The staggered-layered structure, which is only observed in severely deformed crystals, exhibits a preferential scattering on heat-carrying phonons rather than charge-carrying electrons, thus resulting in an ultralow lattice thermal conductivity while retaining high-weight carrier mobility. Moreover, the staggered-layer structure is located adjacent to the van der Waals gap in Bi2(Te, Se)3 lattice and is able to strengthen the interaction between anion layers across the gap, leading to obviously improved compressive strength and Vickers hardness. Consequently, a high peak figure of merit ZT of ≈ 1.3 at 423 K, and an average ZT of ≈ 1.2 at 300-473 K can be achieved in GD sample. This study demonstrates that the GD process can successfully decouple the electrical and thermal transports with simultaneously enhanced mechanic performance.

TMEM16 and TMEM63/OSCA proteins share a conserved potential to permeate ions and phospholipids.

The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-activated OSCA/TMEM63 proteins belong to the Transmembrane Channel/Scramblase (TCS) superfamily. Within the superfamily, OSCA/TMEM63 proteins, as well as TMEM16A and TMEM16B, likely function solely as ion channels. However, the remaining TMEM16 members, including TMEM16F, maintain an additional function as scramblases, rapidly exchanging phospholipids between leaflets of the membrane. Although recent studies have advanced our understanding of TCS structure-function relationships, the molecular determinants of TCS ion and lipid permeation remain unclear. Here we show that single lysine mutations in transmembrane helix (TM) 4 allow non-scrambling TCS members to permeate phospholipids. This study highlights the key role of TM 4 in controlling TCS ion and lipid permeation and offers novel insights into the evolution of the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 family maintains a conserved potential to permeate ions and phospholipids.

Chromatin region binning of gene expression for improving embryo cell subtype identification.

Mammalian embryonic development is a complex process, characterized by intricate spatiotemporal dynamics and distinct chromatin preferences. However, the quick diversification in early embryogenesis leads to significant cellular diversity and the sparsity of scRNA-seq data, posing challenges in accurately determining cell fate decisions. In this study, we introduce a chromatin region binning method using scChrBin, designed to identify chromatin regions that elucidate the dynamics of embryonic development and lineage differentiation. This method transforms scRNA-seq data into a chromatin-based matrix, leveraging genomic annotations. Our results showed that the scChrBin method achieves high accuracy, with 98.0% and 89.2% on two single-cell embryonic datasets, demonstrating its effectiveness in analyzing complex developmental processes. We also systematically and comprehensively analysis of these key chromatin binning regions and their associated genes, focusing on their roles in lineage and stage development. The perspective of chromatin region binning method enables a comprehensive analysis of transcriptome data at the chromatin level, allowing us to unveil the dynamic expression of chromatin regions across temporal and spatial development. The tool is available as an application at https://github.com/liameihao/scChrBin.

Mesenchymal stem cell-derived exosomes in myocardial infarction: Therapeutic potential and application.

Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects. These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome-carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell-free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC-derived exosomes and employing transgenic MSC-derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

ABSTRACT: Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity, activation mechanism, and role in RBC biology and disease remain elusive. Here, we demonstrate that TMEM16F, the long-sought-after RBC CaPLSase, is activated by calcium influx through the mechanosensitive channel PIEZO1 in RBCs. PIEZO1-TMEM16F functional coupling is enhanced in RBCs from individuals with hereditary xerocytosis (HX), an RBC disorder caused by PIEZO1 gain-of-function channelopathy. Enhanced PIEZO1-TMEM16F coupling leads to an increased propensity to expose PS, which may serve as a key risk factor for HX clinical manifestations including anemia, splenomegaly, and postsplenectomy thrombosis. Spider toxin GsMTx-4 and antigout medication benzbromarone inhibit PIEZO1, preventing force-induced echinocytosis, hemolysis, and PS exposure in HX RBCs. Our study thus reveals an activation mechanism of TMEM16F CaPLSase and its pathophysiological function in HX, providing insights into potential treatment.

Deciphering the decisive factors driving fate bifurcations in somatic cell reprogramming.

Single-cell studies have demonstrated that somatic cell reprogramming is a continuous process of cell fates transition. Only partial reprogramming intermediates can overcome the molecular bottlenecks to acquire pluripotency. To decipher the underlying decisive factors driving cell fate, we identified induced pluripotent stem cells or stromal-like cells (iPSCs/SLCs) and iPSCs or trophoblast-like cells (iPSCs/TLCs) fate bifurcations by reconstructing cellular trajectory. The mesenchymal-epithelial transition and the activation of pluripotency networks are the main molecular series in successful reprogramming. Correspondingly, intermediates diverge into SLCs accompanied by the inhibition of cell cycle genes and the activation of extracellular matrix genes, whereas the TLCs fate is characterized by the up-regulation of placenta development genes. Combining putative gene regulatory networks, seven (Taf7, Ezh2, Klf2, etc.) and three key factors (Cdc5l, Klf4, and Nanog) were individually identified as drivers of the successful reprogramming by triggering downstream pluripotent networks during iPSCs/SLCs and iPSCs/TLCs fate bifurcation. Conversely, 11 factors (Cebpb, Sox4, Junb, etc.) and four factors (Gata2, Jund, Ctnnb1, etc.) drive SLCs fate and TLCs fate, respectively. Our study sheds new light on the understanding of decisive factors driving cell fate, which is helpful for improving reprogramming efficiency through manipulating cell fates to avoid alternative fates.

Endothelial TMEM16F lipid scramblase regulates angiogenesis.

Dynamic loss of lipid asymmetry through the activation of TMEM16 Ca2+-activated lipid scramblases (CaPLSases) has been increasingly recognized as an essential membrane event in a wide range of physiological and pathological processes, including blood coagulation, microparticle release, bone development, pain sensation, cell-cell fusion, and viral infection. Despite the recent implications of TMEM16F CaPLSase in vascular development and endothelial cell-mediated coagulation, its signaling role in endothelial biology remains to be established. Here, we show that endothelial TMEM16F regulates in vitro and in vivo angiogenesis through intracellular signaling. Developmental retinal angiogenesis is significantly impaired in TMEM16F deficient mice, as evidenced by fewer vascular loops and larger loop areas. Consistent with our in vivo observation, TMEM16F siRNA knockdown in human umbilical vein endothelial cells compromises angiogenesis in vitro. We further discovered that TMEM16F knockdown enhances VE-cadherin phosphorylation and reduces its expression. Moreover, TMEM16F knockdown also promotes Src kinase phosphorylation at tyrosine 416, which may be responsible for downregulating VE-cadherin expression. Our study thus uncovers a new biological function of TMEM16F in angiogenesis and provides a potential mechanism for how the CaPLSase regulates angiogenesis through intracellular signaling.

Niclosamide potentiates TMEM16A and induces vasoconstriction.

The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered as a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease, but was recently found to possess broad-spectrum off-target effects. Here we show that, under physiological conditions, niclosamide acutely potentiates TMEM16A without having any inhibitory effect. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering niclosamide as a TMEM16A inhibitor to treat diseases such as asthma, COPD, and hypertension. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation, shining light on developing specific TMEM16A modulators to treat human diseases.

NUCLEOLIN PROMOTES AUTOPHAGY THROUGH PGC-1Α IN LPS-INDUCED MYOCARDIAL INJURY.

ABSTRACT: As a multifunctional protein, nucleolin can participate in a variety of cellular processes. Nucleolin also has multiple protective effects on heart disease. Previous studies have shown that nucleolin could not only resist oxidative stress damage and inflammatory damage, but also regulate autophagy to play a protective role in cardiac ischemia. However, the specific mechanism has not been fully elucidated in LPS-induced myocardial injury. Therefore, the aim of this study is to explore the underlying mechanism by which nucleolin regulates autophagy to protect against LPS-induced myocardial injury in vivo and in vitro . In our study, we found that nucleolin could bind to PGC-1α, and we predicted that this interaction could promote autophagy and played a role in inhibiting cardiomyocyte apoptosis. Downregulation of nucleolin in H9C2 cells resulted in decreased autophagy and increased cell apoptosis during LPS-induced myocardial injury, while upregulation of PGC-1α had the opposite protective effect. Upregulation of nucleolin expression in cardiomyocytes could increase the level of autophagy during LPS-induced myocardial injury. In contrast, interference with PGC-1α expression resulted in a decrease in the protective effect of nucleolin, leading to reduced autophagy and thus increasing apoptosis. By using tandem fluorescent-tagged LC3 autophagic flux detection system, we observed autophagic flux and determined that PGC-1α interference could block autophagic lysosomal progression. We further tested our hypothesis in the nucleolin cardiac-specific knockout mice. Finally, we also found that inhibition of autophagy can reduce mitochondrial biogenesis as well as increase apoptosis, which demonstrated the importance of autophagy. Therefore, we can speculate that nucleolin can protect LPS-induced myocardial injury by regulating autophagy, and this protective effect may be mediated by the interaction with PGC-1α, which can positively regulate the ULK1, an autophagy-related protein. Our study provides a new clue for the cardioprotective effect of nucleolin, and may provide new evidence for the treatment of LPS-induced myocardial injury through the regulation of autophagy.

Integrated analysis of ovarian cancer patients from prospective transcription factor activity reveals subtypes of prognostic significance.

Transcription factors are protein molecules that act as regulators of gene expression. Aberrant protein activity of transcription factors can have a significant impact on tumor progression and metastasis in tumor patients. In this study, 868 immune-related transcription factors were identified from the transcription factor activity profile of 1823 ovarian cancer patients. The prognosis-related transcription factors were identified through univariate Cox analysis and random survival tree analysis, and two distinct clustering subtypes were subsequently derived based on these transcription factors. We assessed the clinical significance and genomics landscape of the two clustering subtypes and found statistically significant differences in prognosis, response to immunotherapy, and chemotherapy among ovarian cancer patients with different subtypes. Multi-scale Embedded Gene Co-expression Network Analysis was used to identify differential gene modules between the two clustering subtypes, which allowed us to conduct further analysis of biological pathways that exhibited significant differences between them. Finally, a ceRNA network was constructed to analyze lncRNA-miRNA-mRNA regulatory pairs with differential expression levels between two clustering subtypes. We expected that our study may provide some useful references for stratifying and treating patients with ovarian cancer.

Kilogram-scale fabrication of TiO2 nanoparticles modified with carbon dots with enhanced visible-light photocatalytic activity.

Incorrect discharge of dye wastewater will cause environment pollution and be very harmful to human health. Visible-light photocatalysis over large-scale synthesized semiconductor materials can become one of the feasible solutions for the practical application of purifying dye wastewater. As a new candidate, carbon dots (CDs) with unique fluorescence were fabricated on a tens of grams scale and then further applied to the kilogram-scale synthesis of a CDs/TiO2 composite by one-step heat treatment. Compared with single TiO2 nanoparticles (NPs), the CDs/TiO2 composite with a large specific surface area exhibits enhanced photo-degradation performance for methyl orange (MO). This phenomenon can be attributed to the loading of CDs in the TiO2 NPs, which is conducive to broadening the light absorption spectrum and improving absorption intensity, narrowing the band gap, charge carrier trapping, up-converting properties, and charge separation. The kilogram-scale synthesis of the CDs/TiO2 photocatalyst does not affect the morphology, structure, optical properties and photocatalytic performance of the composite, which opens up a new avenue to construct elaborate heterostructures for enhanced photocatalytic performance using visible light as the light source.

A deep capsule neural network with data augmentation generative adversarial networks for single and simultaneous fault diagnosis of wind turbine gearbox.

The fault diagnosis (FD) of wind turbine gearbox (WTG) is of special importance for keeping the wind turbine drivetrain working normally and safely. However, owing to the limited training data and the mutual interference of various mechanical parts, it is of great difficulty to realize the simultaneous-fault monitoring task of WTG using existing intelligent FD methods or manual inspection-based approaches. To tackle the issue, a deep capsule neural network with data augmentation generative adversarial networks, named ST-DAGANs-CapNet, is developed for the single and simultaneous FD of WTG by integrating capsule neural network (CapsNet) with Stockwell transform (ST) and data augmentation generative adversarial networks (DAGANs). The proposed ST-DAGANs-CapNet method mainly consists of three steps. First of all, ST is adopted to extract two-dimension (2-d) image features of time-frequency domain from raw time-domain vibration signals of WTG. Then, DAGANs are employed for generating more fake image samples to address the problem of lacking training data. At last, the built CapsNet model is utilized to diagnose the single and compound faults of WTG by the primary 2-d feature images and the made fake 2-d feature images in training set. Two experimental studies are implemented to prove the effectiveness of the proposed method, and the result is compared with some existing intelligent FD of WTG. It indicates that DAGANs are effective in helping to tackle the issue of limited and unbalanced training samples in real FD of WTG, and the diagnosis result of the proposed approach in test sample set is better than that of several commonly used FD methods in literatures.

ZnO Nanoparticles Modified by Carbon Quantum Dots for the Photocatalytic Removal of Synthetic Pigment Pollutants.

Synthetic pigment pollutants caused by the rapid development of the modern food industry have become a serious threat to people's health and quality of life. Environmentally friendly ZnO-based photocatalytic degradation exhibits satisfactory efficiency, but some shortcomings of large band gap and rapid charge recombination reduce the removal of synthetic pigment pollutants. Here, carbon quantum dots (CQDs) with unique up-conversion luminescence were applied to decorate ZnO nanoparticles to effectively construct the CQDs/ZnO composites via a facile and efficient route. The ZnO nanoparticles with a spherical-like shape obtained from a zinc-based metal organic framework (zeolitic imidazolate framework-8, ZIF-8) were coated by uniformly dispersive quantum dots. Compared with single ZnO particles, the obtained CQDs/ZnO composites exhibit enhanced light absorption capacity, decreased photoluminescence (PL) intensity, and improved visible-light degradation for rhodamine B (RhB) with the large apparent rate constant (k app). The largest k app value in the CQDs/ZnO composite obtained from 75 mg of ZnO nanoparticles and 12.5 mL of the CQDs solution (∼1 mg·mL-1) was 2.6 times that in ZnO nanoparticles. This phenomenon may be attributed to the introduction of CQDs, leading to the narrowed band gap, an extended lifetime, and the charge separation. This work provides an economical and clean strategy to design visible-light-responsive ZnO-based photocatalysts, which is expected to be used for the removal of synthetic pigment pollutants in food industry.