Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors.

In early embryonic development, the cross-regulation of transcription factors and signaling pathways are critical in mediating developmental and physiological processes. Additionally, many studies have shown the importance of post-transcriptional regulation of signaling and network components mediated by microRNAs (miRNAs); however, how miRNAs are transcriptionally regulated is poorly understood. miRNAs are critical fine-tuners of many biological processes and their dysregulation leads to a variety of diseases and developmental defects. Previously, we have shown that miRNAs are dynamically expressed throughout sea urchin development, suggesting that miRNAs are likely to be under transcriptional regulation. Here, we used pharmacological inhibitors, genetic constructs, and loss-of-function reagents to assess the impact of key signaling pathways (Wnt, Nodal, MAPK, Sonic Hedgehog, Delta/Notch, VEGF, and BMP) and transcription factors (Alx1, Ets1/2, and Tbr) on the transcript levels of the evolutionarily conserved miR-1, miR-31, miR-92 and miR-124; the invertebrate-specific miR-71; and the echinoderm-specific miR-2002, miR-2007, and miR-2012. We also used computational methods to identify potential transcription factor binding sites of these miRNAs. Lists of binding motifs for transcription factors (TFs) were acquired from the MEME-Suite Motif Database and used as inputs for the algorithm FIMO (Find Individual Motif Occurrences), which detects short nucleotide motifs within larger sequences. Based on experimental data on miRNA expression in conjunction with bioinformatic predictions, we propose that the transcription factors Tbr, Alx1, and Ets1 regulate SpmiR-1, SpmiR-31, and SpmiR-71, respectively. We additionally observed significant effects on miRNA levels as a result of perturbations to Wnt, Nodal, MAPK, and Sonic Hedgehog signaling pathways, while no significant change on miRNA levels were observed with perturbations to Delta/Notch, VEGF, or BMP signaling pathways. Overall, this study provides insights into the transcriptional regulation of miRNAs by signaling pathways and transcription factors and contribute to our overall understanding of the genetic regulation of developmental processes.

miR-153 promotes neural differentiation by activating the cell adhesion/Ca2+ signaling pathway and targeting ion channel activity in HT-22 cells by bioinformatic analysis.

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid ß-protein (Aß) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aß toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.

What we learned from the COVID-19 infection control and what we need in the future, a quantitative and qualitative study on hospital infection prevention and control practitioners (HIPCPs) in Tianjin, China.

BACKGROUND: In December 2022, the epidemic prevention and control policy was upgraded and China came to a different stage of epidemic control. There have been no studies from the perspective of infection prevention and control practitioners (HIPCP) about the historic surge. OBJECTIVE: To understand the needs of the healthcare system during the epidemic and to identify implications for better healthcare supply and infection control in the future. METHODS: A longitudinal quantitative and qualitative study was performed based on two comprehensive questionnaire surveys among 497 HIPCPs before and during the epidemic peak in Tianjin, China. RESULTS: The workload (8.2 hours vs 10.14 hours, P = 0) and self-reported mental health problems (23.5% vs. 61.8%, P < 0.05) among the HIPCPs increased significantly in the peak period. Ward reconstruction and resource coordination were the most needed jobs in hospital infection control, and rapidly increased medical waste during the epidemic needs to be considered in advance. Community support for healthcare personnel and their families, maintaining full PPE to reduce simultaneous infection of medical staff, and clinical training of infectious diseases for medical staff, especially doctors in advance are the most important things we learned. CONCLUSION: Although it has been four years since the first outbreak of COVID-19, more improvements should be made to prepare for the next wave of COVID-19 or other diseases.

In-situ synthesis Fe3C@C/rGO as matrix for high performance lithium-sulfur batteries at room and low temperatures.

People have been focusing on how to improve the specific capacity and cycling stability of lithium-sulfur batteries at room temperature, however, on some special occasions such as cold cities and aerospace fields, the operating temperature is low, which dramatically hinders the performance of batteries. Here, we report an iron carbide (Fe3C)/rGO composite as electrode host, the Fe3C nanoparticles in the composite have strong adsorption and high catalytic ability for polysulfide. The rGO makes the distribution of Fe3C nanoparticles more disperse, and this specific structure makes the deposition of Li2S more uniform. Therefore, it realizes the rapid transformation and high performance of lithium-sulfur batteries at both room and low temperatures. At room temperature, after 100 cycles at 1C current density, the reversible specific capacity of the battery can be stabilized at 889 ± 7.1 mAh/g. Even at -40 °C, in the first cycle battery still emits 542.9 ± 3.7 mAh/g specific capacity. This broadens the operating temperature for lithium-sulfur batteries and also provides a new idea for the selection of host materials for sulfur in low-temperature lithium-sulfur batteries.

Study on the thermal behaviour of spontaneous combustion of open-pit minerals.

To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.

Combined cardiac, lung, and diaphragm ultrasound for predicting weaning failure during spontaneous breathing trial.

BACKGROUND: Weaning from invasive mechanical ventilation (MV) is a complex and challenging process that involves multiple pathophysiological mechanisms. A combined ultrasound evaluation of the heart, lungs, and diaphragm during the weaning phase can help to identify risk factors and underlying mechanisms for weaning failure. This study aimed to investigate the accuracy of lung ultrasound (LUS), transthoracic echocardiography (TTE), and diaphragm ultrasound for predicting weaning failure in critically ill patients. METHODS: Patients undergoing invasive MV for > 48 h and who were readied for their first spontaneous breathing trial (SBT) were studied. Patients were scheduled for a 2-h SBT using low-level pressure support ventilation. LUS and TTE were performed prospectively before and 30 min after starting the SBT, and diaphragm ultrasound was only performed 30 min after starting the SBT. Weaning failure was defined as failure of SBT, re-intubation, or non-invasive ventilation within 48 h. RESULTS: Fifty-one patients were included, of whom 15 experienced weaning failure. During the SBT, the global, anterior, and antero-lateral LUS scores were higher in the failed group than in the successful group. Receiver operating characteristic curve analysis showed that the areas under the curves for diaphragm thickening fraction (DTF) and global and antero-lateral LUS scores during the SBT to predict weaning failure were 0.678, 0.719, and 0.721, respectively. There was no correlation between the LUS scores and the average E/e' ratio during the SBT. Multivariate analysis identified antero-lateral LUS score > 7 and DTF < 31% during the SBT as independent predictors of weaning failure. CONCLUSION: LUS and diaphragm ultrasound can help to predict weaning failure in patients undergoing an SBT with low-level pressure support. An antero-lateral LUS score > 7 and DTF < 31% during the SBT were associated with weaning failure.

RNA-seq-based comparative transcriptome analysis reveals the role of CsPrx73 in waterlogging-triggered adventitious root formation in cucumber.

Abiotic stressors like waterlogging are detrimental to cucumber development and growth. However, comprehension of the highly complex molecular mechanism underlying waterlogging can provide an opportunity to enhance cucumber tolerance under waterlogging stress. We examined the hypocotyl and stage-specific transcriptomes of the waterlogging-tolerant YZ026A and the waterlogging-sensitive YZ106A, which had different adventitious rooting ability under waterlogging. YZ026A performed better under waterlogging stress by altering its antioxidative machinery and demonstrated a greater superoxide ion (O 2-) scavenging ability. KEGG pathway enrichment analysis showed that a high number of differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis. By pairwise comparison and weighted gene co-expression network analysis analysis, 2616 DEGs were obtained which were categorized into 11 gene co-expression modules. Amongst the 11 modules, black was identified as the common module and yielded a novel key regulatory gene, CsPrx73. Transgenic cucumber plants overexpressing CsPrx73 enhance adventitious root (AR) formation under waterlogging conditions and increase reactive oxygen species (ROS) scavenging. Silencing of CsPrx73 expression by virus-induced gene silencing adversely affects AR formation under the waterlogging condition. Our results also indicated that CsERF7-3, a waterlogging-responsive ERF transcription factor, can directly bind to the ATCTA-box motif in the CsPrx73 promoter to initiate its expression. Overexpression of CsERF7-3 enhanced CsPrx73 expression and AR formation. On the contrary, CsERF7-3-silenced plants decreased CsPrx73 expression and rooting ability. In conclusion , our study demonstrates a novel CsERF7-3-CsPrx73 module that allows cucumbers to adapt more efficiently to waterlogging stress by promoting AR production and ROS scavenging.

CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR-1246/PEG3 signaling.

Ischemia‒reperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.

Identification of cuproptosis-realated key genes and pathways in Parkinson's disease via bioinformatics analysis.

INTRODUCTION: Parkinson's disease (PD) is the second most common worldwide age-related neurodegenerative disorder without effective treatments. Cuproptosis is a newly proposed conception of cell death extensively studied in oncological diseases. Currently, whether cuproptosis contributes to PD remains largely unclear. METHODS: The dataset GSE22491 was studied as the training dataset, and GSE100054 was the validation dataset. According to the expression levels of cuproptosis-related genes (CRGs) and differentially expressed genes (DEGs) between PD patients and normal samples, we obtained the differentially expressed CRGs. The protein-protein interaction (PPI) network was achieved through the Search Tool for the Retrieval of Interacting Genes. Meanwhile, the disease-associated module genes were screened from the weighted gene co-expression network analysis (WGCNA). Afterward, the intersection genes of WGCNA and PPI were obtained and enriched using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the key genes were identified from the datasets. The receiver operating characteristic curves were plotted and a PPI network was constructed, and the PD-related miRNAs and key genes-related miRNAs were intersected and enriched. Finally, the 2 hub genes were verified via qRT-PCR in the cell model of the PD and the control group. RESULTS: 525 DEGs in the dataset GSE22491 were identified, including 128 upregulated genes and 397 downregulated genes. Based on the PPI network, 41 genes were obtained. Additionally, the dataset was integrated into 34 modules by WGCNA. 36 intersection genes found from WGCNA and PPI were significantly abundant in 7 pathways. The expression levels of the genes were validated, and 2 key genes were obtained, namely peptidase inhibitor 3 (PI3) and neuroserpin family I member 1 (SERPINI1). PD-related miRNAs and key genes-related miRNAs were intersected into 29 miRNAs including hsa-miR-30c-2-3p. At last, the qRT-PCR results of 2 hub genes showed that the expressions of mRNA were up-regulated in PD. CONCLUSION: Taken together, this study demonstrates the coordination of cuproptosis in PD. The key genes and miRNAs offer novel perspectives in the pathogenesis and molecular targeting treatment for PD.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes.

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.

The detection methods currently available for protein aggregation in neurological diseases.

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

COAP-Pd Catalyzed Asymmetric Formal [3+2] Cycloaddition for Optically Active Multistereogenic Spiro Cyclopentane-Indandiones Bearing Cyclic N-Sulfonyl Ketimine Skeletons.

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

Ultrafast polarization characterization with Mueller matrix based on optical time-stretch and spectral encoding.

High-speed optical polarization characterization is highly desirable for a wide range of applications, including remote sensing, telecommunication, and medical diagnosis. The utilization of the Mueller matrix provides a superior systematic and comprehensive approach to represent polarization attributes when matter interacts with optical beams. However, the current measurement speed of Mueller matrix is limited to only seconds or milliseconds. In this study, we present an ultrafast Mueller matrix polarimetry (MMP) technique based on optical time-stretch and spectral encoding that enables us to achieve an impressive temporal resolution of 4.83 nanoseconds for accurate Mueller matrix measurements. The unique feature of optical time-stretch technology enables continuous, ultrafast single-shot spectroscopy, resulting in a remarkable speed of up to 207 MHz for spectral encoding Mueller matrix measurement. We have employed an effective Mueller linear reconstruction algorithm based on the measured modulation matrix, accounting for all potential non-ideal effects of polarization components like retardance error and azimuth error. To ensure high precision, prior to the actual measurement, high-order dispersion induced by time-stretch requires adjustment through proper modulation matrix design. Upon such correction, both the results of static and rapid dynamic samples measurements exhibit exceptional accuracy with root-mean-square error (RMSE) approximately equal to 0.04 and 0.07 respectively. This presented ultrafast MMP provides a significant advance over preceding endeavors, enabling superior accuracy and increased speed concurrently.

Local CO Generator Enabled by a CO-Producing Core for Kinetically Enhancing Electrochemical CO2 Reduction to Multicarbon Products.

CO plays a crucial role as an intermediate in electrochemical CO2 conversion to generate multicarbon (C2+) products. However, optimizing the coverage of the CO intermediate (*CO) to improve the selectivity of C2+ products remains a great challenge. Here, we designed a hierarchically structured double hollow spherical nanoreactor featuring atomically dispersed nickel (Ni) atoms as the core and copper (Cu) nanoparticles as the shell, which can greatly improve the catalytic activity and selectivity for C2+ compounds. Within this configuration, CO generated at the active Ni sites on the inner layer accumulates in the cavity before spilling over neighboring Cu sites on the outer layer, thus enhancing CO dimerization within the cavity. Notably, this setup achieves a sustained faradaic efficiency of 74.4% for C2+ production, with partial current densities reaching 337.4 mA cm-2. In situ Raman spectroscopy and finite-element method (FEM) simulations demonstrate that the designed local CO generator can effectively increase the local CO concentration and restrict CO evolution, ultimately boosting C-C coupling. The hierarchically ordered architectural design represents a promising solution for achieving highly selective C2+ compound production in the electroreduction of CO2.

Magnetism and electronic properties of ConMoP (n = 1 ~ 5) cluster: a DFT study.

CONTEXT: Hydrogen has emerged as a promising clean energy carrier, underscoring the imperative need to comprehend its adsorption mechanisms. This study delves into the magnetic and electronic properties of Co-Mo-P clusters, aiming to unveil their catalytic potential in hydrogen production. Employing density functional theory (DFT), we optimized cluster configurations and scrutinized their magnetic behaviors. Our investigation unveiled 16 stable configurations of the ConMoP (n = 1 ~ 5) cluster, predominantly in steric forms. The magnetic attributes were primarily ascribed to the d orbitals of Co metal atoms, with Co3MoP exhibiting exceptional magnetic characteristics. Analysis of density of state diagrams revealed the prevalence of spin-up α-electrons in d orbitals, while spin-down ß-electrons attenuated overall magnetic properties. Localized orbital (LOL) analysis highlighted stable covalent bonds within the clusters, affirming their catalytic potential. Orbital delocalization index (ODI) analysis revealed diverse spatial distribution ranges for orbitals across different configurations, suggesting a progressive attenuation of off-domain properties with increasing cluster size. Furthermore, infrared spectroscopy unveiled distinct vibrational peaks in various configurations, indicative of unique infrared activities. These findings contribute to a nuanced theoretical understanding of Co-Mo-P clusters and pave the path for future research aimed at augmenting their catalytic efficiency in hydrogen production. This study underscores the viability of Co-Mo-P clusters as alternatives to conventional Pt catalysts, offering insights into the design of novel materials for sustainable energy applications. Further research is warranted to explore the behavior of the Co-Mo-P system under diverse reaction conditions, fostering advancements in materials and energy science. METHODS: In this study, we harnessed the ConMoP (n = 1 ~ 5) cluster as a simulation platform for probing the local structure of the material. Our aim was to scrutinize the magnetism, electronic characteristics influenced by the varying metal atoms within these clusters. A systematic exploration involved incrementing the number of metal atoms and expanding the cluster size to elucidate the corresponding property variations. Density functional theory (DFT) calculations were pivotal to our methodology, employing the B3LYP hybrid functional implemented in the Gaussian 16 software package. The ConMoP (n = 1 ~ 5) cluster underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, yielding optimized configurations with diverse spin multiplet degrees. To comprehensively characterize and visually represent the stability, electronic features, and catalytic attributes of these configurations, we employed a suite of computational tools. Specifically, quantum chemistry software GaussView and wave function analysis software Multiwfn played integral roles. Through the integrated use of these computational tools, we acquired valuable insights into the magnetism, electronic characteristics of the ConMoP (n = 1 ~ 5) cluster, shedding light on their dependency on distinct metal atoms.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia with severe clinical sequelae, but its genetic characteristic implicated in pathogenesis has not been completely clarified. Accumulating evidence has indicated that circulating exosomes and their carried cargoes, such as long non-coding RNAs (lncRNAs), involve in the progress of multiple cardiovascular diseases. However, their potential role as clinical biomarkers in AF diagnosis and prognosis remains unknown. Methods: Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients. Results: A total of 53 differentially expressed lncRNAs were identified, and a total of 6 significantly changed lncRNAs (fold change > 2.0), including NR0046235, NR003045, NONHSAT167247.1, NONHSAT202361.1, NONHSAT205820.1 and NONHSAT200958.1, were verified by qRT-PCR in 215 participants. Moreover, these circulating exosome lncRNA levels were different between paroxysmal and persistent AF patients, which were dramatically associated with abnormal hemodynamics and atrial diameter. Furthermore, we observed that the area under ROC curve (AUC) of six lncRNAs combination for diagnosis of persistent AF was 80.34%. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analysis indicated these exosome lncRNAs mainly concerning response to chemokine-chemokine receptor interaction, which induced activated inflammation and structural remodeling. In addition, increased plasma levels of CXCR3 ligands, including CXCL4, CXCL9, CXCL10 and CXCL11, were accumulated in AF patient tissues. Conclusion: Our study provides the transcriptome profile revealing pattern of circulating exosome lncRNAs in atrial structural remodeling, which bring valuable insights into improving prognosis and therapeutic targets for AF.

Hemodynamic Effects of Tortuosity and Stenosis in Superficial Temporal Artery-Middle Cerebral Artery Bypass for Moyamoya Disease.

BACKGROUND: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery has been widely adopted in treating moyamoya disease (MMD). Geometric variations including high tortuosity and stenosis exist in many cases, but the hemodynamic effects have not been comprehensively evaluated. We aim to evaluate the hemodynamic effects of bypass geometry variations based on patient-specific data. METHODS: In total, 17 patients with MMD who underwent STA-MCA bypass surgery with highly tortuous bypass geometry were included. For each patient, the original 3-dimensional structure of STA-MCA bypass was reconstructed from clinical imaging data. The bypass structure was virtually improved by removing the tortuosity and stenosis. Computational fluid dynamics simulation was performed on both bypass structures under identical patient-specific condition. The simulated hemodynamic parameters of the bypass and its distal branches were compared between the original and virtually improved bypass geometries in all cases using paired t-test or Wilcoxon signed-rank test. The changes of hemodynamic parameters were compared between the cases with and without mild-to-moderate stenosis (44.0-70.3% in diameter) in the bypass using t-test or Mann-Whitney U test. RESULTS: The virtual improvement of bypass geometry significantly increased the flow rate of the bypass and its distal branches (P < 0.05) and decreased the transcranial flow resistance (P < 0.05). The hemodynamic changes in cases with stenosis removal were significantly greater than those without stenosis (P < 0.05). CONCLUSIONS: High tortuosity and stenosis can significantly change the hemodynamics of STA-MCA bypass, and the optimization of bypass geometry deserves further consideration.

Rational design of soluble expressed human aldehyde dehydrogenase 2 with high stability and activity in pepsin and trypsin.

Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme in alcohol metabolism, and oral administration of ALDH2 is a promising method for alcohol detoxification. However, recombinant ALDH2 is susceptible to hydrolysis by digestive enzymes in the gastrointestinal tract and is expressed as inactive inclusion bodies in E. coli. In this study, we performed three rounds of rational design to address these issues. Specifically, the surface digestive sites of pepsin and trypsin were replaced with other polar amino acids, while hydrophobic amino acids were incorporated to reshape the catalytic cavity of ALDH2. The resulting mutant DE2-852 exhibited a 45-fold increase in soluble expression levels, while its stability against trypsin and pepsin increased by eightfold and twofold, respectively. Its catalytic efficiency (kcat/Km) at pH 7.2 and 3.2 improved by more than four and five times, respectively, with increased Vmax and decreased Km values. The enhanced properties of DE2-852 were attributed to the D457Y mutation, which created a more compact protein structure and facilitated a faster collision between the substrate and catalytic residues. These results laid the foundation for the oral administration and mass preparation of highly active ALDH2 and offered insights into the oral application of other proteins.