A chromosome-level genome assembly of an avivorous bat species (Nyctalus aviator).

Currently, three carnivorous bat species, namely Ia io, Nyctalus lasiopterus, and Nyctalus aviator, are known to actively prey on seasonal migratory birds (hereinafter referred to as "avivorous bats"). However, the absence of reference genomes impedes a thorough comprehension of the molecular adaptations of avivorous bat species. Herein, we present the high-quality chromosome-scale reference genome of N. aviator based on PacBio subreads, DNBSEQ short-reads and Hi-C sequencing data. The genome assembly size of N. aviator is 1.77 Gb, with a scaffold N50 of 102 Mb, of which 99.8% assembly was anchored into 21 pseudo-chromosomes. After masking 635.1 Mb repetitive sequences, a total of 19,412 protein-coding genes were identified, of which 99.3% were functionally annotated. The genome assembly and gene prediction reached 96.1% and 96.1% completeness of Benchmarking Universal Single-Copy Orthologs (BUSCO), respectively. This chromosome-level reference genome of N. aviator fills a gap in the existing information on the genomes of carnivorous bats, especially avivorous ones, and will be valuable for mechanism of adaptations to dietary niche expansion in bat species.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. Activating transcription factor (ATF) 3 has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 (activating transcription factor 3) in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adenoassociated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II (angiotensin II)-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Dihalogenated nitrophenols in drinking water: Prevalence, resistance to household treatment, and cardiotoxic impact on zebrafish embryo.

Dihalogenated nitrophenols (2,6-DHNPs), an emerging group of aromatic disinfection byproducts (DBPs) detected in drinking water, have limited available information regarding their persistence and toxicological risks. The present study found that 2,6-DHNPs are resistant to major drinking water treatment processes (sedimentation and filtration) and households methods (boiling, filtration, microwave irradiation, and ultrasonic cleaning). To further assess their health risks, we conducted a series of toxicology studies using zebrafish embryos as the model organism. Our findings reveal that these emerging 2,6-DHNPs showed lethal toxicity 248 times greater than that of the regulated DBP, dichloroacetic acid. Specifically, at sublethal concentrations, exposure to 2,6-DHNPs generated reactive oxygen species (ROS), caused apoptosis, inhibited cardiac looping, and induced cardiac failure in zebrafish. Remarkably, the use of a ROS scavenger, N-acetyl-l-cysteine, considerably mitigated these adverse effects, emphasizing the essential role of ROS in 2,6-DHNP-induced cardiotoxicity. Our findings highlight the cardiotoxic potential of 2,6-DHNPs in drinking water even at low concentrations of 19 µg/L and the beneficial effect of N-acetyl-l-cysteine in alleviating the 2,6-DHNP-induced cardiotoxicity. This study underscores the urgent need for increased scrutiny of these emerging compounds in public health discussions.

Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.

Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.

Pulmonary Transit Time Assessment by CEUS in Healthy Rabbits: Feasibility, and the Effects of UCAs Dilution Concentration.

To evaluate the inter-observer variability and the intra-observer repeatability of pulmonary transit time (PTT) measurement using contrast-enhanced ultrasound (CEUS) in healthy rabbits, and assess the effects of dilution concentration of ultrasound contrast agents (UCAs) on PTT. Thirteen healthy rabbits were selected, and five concentrations UCAs of 1:200, 1:100, 1:50, 1:10, and 1:1 were injected into the right ear vein. Five digital loops were obtained from the apical 4-chamber view. Four sonographers obtained PTT by plotting the TIC of right atrium (RA) and left atrium (LA) at two time points (T1 and T2). The frame counts of the first appearance of UCAs in RA and LA had excellent inter-observer agreement, with intra-class correlations (ICC) of 0.996, 0.988, respectively. The agreement of PTT among four observers was all good at five different concentrations, with an ICC of 0.758-0.873. The reproducibility of PTT obtained by four observers at T1 and T2 was performed well, with ICC of 0.888-0.961. The median inter-observer variability across 13 rabbits was 6.5% and the median variability within 14 days for 4 observers was 1.9%, 1.7%, 2.2%, 1.9%, respectively; The PTT of 13 healthy rabbits is 1.01 ± 0.18 second. The difference of PTT between five concentrations is statistically significant. The PTT obtained by a concentration of 1:200 and 1:100 were higher than that of 1:1, while there were no significantly differences in PTT of a concentration of 1:1, 1:10, and 1:50. PTT measured by CEUS in rabbits is feasible, with excellent inter-observer and intra-observer reliability and reproducibility, and dilution concentration of UCAs influences PTT results.

Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in pulmonary arterial hypertension.

BACKGROUND: Extrachromosomal circular DNAs (eccDNAs) have been reported to play a key role in the occurrence and development of various diseases. However, the characterization and role of eccDNAs in pulmonary arterial hypertension (PAH) remain unclear. METHODS: In the discovery cohort, we first explored eccDNA expression profiles by Circle-sequencing analysis. The candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. In the validation cohort, 30 patients with PAH and 10 healthy controls were recruited for qPCR amplification to detect the candidate eccDNAs. Datas at the baseline were collected, including clinical background, biochemical variables, echocardiography and hemodynamic factors. Receiver operating characteristic curve was used to investigate the diagnostic effect of the eccDNA. RESULTS: We identified a total of 21,741 eccDNAs in plasma samples of 3 IPAH patients and 3 individuals in good health, and the expression frequency, GC content, length distribution, and genome distribution of the eccDNAs were thoroughly characterized and analyzed. In the validation cohort, 687 eccDNAs were differentially expressed in patients with IPAH compared with healthy controls (screening threshold: |FC|≥2 and P < 0.05). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the specific eccDNAs in IPAH were significantly enriched in calcium channel activity, the mitogen-activated protein kinase pathway, and the wnt signaling pathway. Verification queue found that the expression of eccDNA-chr2:131208878-131,424,362 in PAH was considerably higher than that in healthy controls and exhibited a high level of accuracy in predicting PAH with a sensitivity of 86.67% and a specificity of 90%. Furthermore, correlation analysis disclosed a significant association between serum eccDNA-chr2:131208878-131,424,362 and mean pulmonary artery pressure (mPAP) (r = 0.396, P = 0.03), 6 min walking distance (6MWD) (r = -0.399, P = 0.029), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = 0.685, P < 0.001) and cardiac index (CI) (r = - 0.419, P = 0.021). CONCLUSIONS: This is the first study to identify and characterize eccDNAs in patients with PAH. We revealed that serum eccDNA-chr2:131208878-131,424,362 is significantly overexpressed and can be used in the diagnosis of PAH, indicating its potential as a novel non-invasive biomarker.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Simultaneously improving the pore structure and electron conductive network of the anode catalyst layer via SnO2 doping for proton exchange membrane water electrolysis.

Proton exchange membrane water electrolysis (PEMWE) is a promising technology for green hydrogen production. However, its large-scale commercial application is limited by its high precious metal loading, because low catalyst loading leads to reduced electron transport channels and decreased water transportation, etc. Herein, we study the electrode level strategy for reducing Ir loading by the optimization of the micro-structure of the anode catalyst layer via SnO2 doping. The pore structure and electron conductive network of the anode catalyst layer can be simultaneously improved by SnO2 doping, under appropriate conditions. Therefore, mass transfer polarization and ohmic polarization of the single cell are reduced. Moreover, the enhanced pore structure and improved electron conduction network collectively contribute to a decreased occurrence of charge transfer polarization. By this strategy, the performance of the single cell with the Ir loading of 1.5 mg cm-2 approaches the single cell with the higher Ir loading of 2.0 mg cm-2, which means that SnO2 doping saves about 25% loading of Ir. This paper provides a perspective at the electrode level to reduce the precious metal loading of the anode in PEMWE.

Observation on the Analgesic Effect of Different Doses of a Combination of Esketamine and Dexmedetomidine Administered for Percutaneous Endoscopic Transforaminal Discectomy: A Randomized, Double-Blind Controlled Trial.

BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.

Integrative informatics analysis identifies that ginsenoside Re improves renal fibrosis through regulation of autophagy.

We previously demonstrated that ginsenoside Re (G-Re) has protective effects on acute kidney injury. However, the underlying mechanism is still unclear. In this study, we conducted a meta-analysis and pathway enrichment analysis of all published transcriptome data to identify differentially expressed genes (DEGs) and pathways of G-Re treatment. We then performed in vitro studies to measure the identified autophagy and fibrosis markers in HK2 cells. In vivo studies were conducted using ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) models to evaluate the effects of G-Re on autophagy and kidney fibrosis. Our informatics analysis identified autophagy-related pathways enriched for G-Re treatment. Treatment with G-Re in HK2 cells reduced autophagy and mRNA levels of profibrosis markers with TGF-ß stimulation. In addition, induction of autophagy with PP242 neutralized the anti-fibrotic effects of G-Re. In murine models with UUO and AAN, treatment with G-Re significantly improved renal function and reduced the upregulation of autophagy and profibrotic markers. A combination of informatics analysis and biological experiments confirmed that ginsenoside Re could improve renal fibrosis and kidney function through the regulation of autophagy. These findings provide important insights into the mechanisms of G-Re's protective effects in kidney injuries.

Krill Oil and Its Bioactive Components as a Potential Therapy for Inflammatory Bowel Disease: Insights from In Vivo and In Vitro Studies.

Krill oil is extracted from krill, a small crustacean in the Antarctic Ocean. It has received growing attention because of krill oil's unique properties and diverse health benefits. Recent experimental and clinical studies suggest that it has potential therapeutic benefits in preventing the development of a range of chronic conditions, including inflammatory bowel disease (IBD). Krill oil is enriched with long-chain n-3 polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, and the potent antioxidant astaxanthin, contributing to its therapeutic properties. The possible underlying mechanisms of krill oil's health benefits include anti-inflammatory and antioxidant actions, maintaining intestinal barrier functions, and modulating gut microbiota. This review aims to provide an overview of the beneficial effects of krill oil and its bioactive components on intestinal inflammation and to discuss the findings on the molecular mechanisms associated with the role of krill oil in IBD prevention and treatment.

Comparison of endoscopic thyroidectomy via the oral vestibule approach and the areola approach for papillary thyroid carcinoma.

BACKGROUND: The endoscopic thyroidectomy areola approach (ETAA) has been widely applied for papillary thyroid carcinoma (PTC), but leaves scars and is not truly minimally invasive. The oral vestibular approach (ETOVA) leaves no scars and is even more minimally invasive. However, there have been few comparative studies of ETAA and ETOVA for PTC. The purpose of our research was to compare two PTC treatment methods in terms of feasibility, safety, efficacy, and cosmetic results. METHODS: A total of 129 patients with PTC underwent thyroidectomy combined with central lymph node dissection by the same surgeon. Among them, 79 patients underwent the ETOVA, and the others underwent the ETAA. We compared the two groups in terms of operative outcomes, postoperative complications, and cosmetic results. RESULTS: No significant differences were found in the clinical characteristics between the ETOVA and ETAA groups. There were no significant differences in the number of removed lymph nodes (P = 0.279) or the number of positive lymph nodes (P = 0.569), but the ETOVA group had a higher number of removed lymph nodes. There was also no significant difference in blood loss volume(P = 0.180), postoperative drainage volume (P = 0.063), length of hospital stay (P = 0.182), transient RLN injury rate (P = 1.000), permanent RLN injury rate (P = 1.000), or recurrence rate (P = 1.000). The ETOVA was a longer operation than the ETAA was (P < 0.01). The ETOVA group had less pain (VAS 1: P < 0.01, VAS 3: P = 0.001), less neck discomfort (1 month after surgery: P = 0.009, 3 months after surgery: P = 0.033), and better cosmetic results (P = 0.001). CONCLUSIONS: The ETOVA is not inferior to the ETAA in terms of safety and curability of PTC and is advantageous in terms of central lymph node dissection, minimal invasiveness, and cosmetic results. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Zhongshan Hospital of Xiamen University (2017 V1.0). No funding was received.

Two-Layer Reinforcement Learning for Output Consensus of Multiagent Systems Under Switching Topology.

In this article, the data-based output consensus of discrete-time multiagent systems under switching topology (ST) is studied via reinforcement learning. Due to the existence of ST, the kernel matrix of value function is switching-varying, which cannot be applied to existing algorithms. To overcome the inapplicability of varying kernel matrix, a two-layer reinforcement learning algorithm is proposed in this article. To further implement the proposed algorithm, a data-based distributed control policy is presented, which is applicable to both fixed topology and ST. Besides, the proposed method does not need assumptions on the eigenvalues of leader's dynamic matrix, it avoids the assumptions in the previous method. Subsequently, the convergence of algorithm is analyzed. Finally, three simulation examples are provided to verify the proposed algorithm.

Dihalogenated nitrophenols exposure induces developmental neurotoxicity in zebrafish embryo.

2,6-Dihalogenated nitrophenols (2,6-DHNPs) are emerging halogenated nitroaromatic pollutants that have been detected in various water environments. However, there is currently limited research available regarding their potential impacts on locomotion behavior and neurotoxicity. Therefore, this study utilized zebrafish embryos to investigate the potential neurotoxic effects of 2,6-DHNPs by examining their impact on the nervous system at a concentration defined as 10% of the median lethal concentration. Our findings demonstrated that exposure to 2,6-DHNPs resulted in a significant 30 % decrease in the total swimming distance of zebrafish larvae, accompanied by notable impairments in motor neuron development and central nervous system. These effects were evidenced by a substantial 25% decrease in axonal growth, as well as disruptions in synapse formation and neuronal differentiation. Additionally, neurotransmitter analysis revealed marked decreases of 40%, 35%, and 30% in dopamine, 5-hydroxytryptamine, and acetylcholine levels respectively, highlighting disturbances in their synthesis, transport, and degradation mechanisms. These results emphasize the considerable neurotoxicity of 2,6-DHNPs at concentrations previously considered safe; thus necessitating a re-evaluation of environmental risk assessments and regulatory standards for such emerging contaminants.

Biomineralized manganese oxide mediated nitrogen-contained wastewater treatment.

In recent years, manganese (Mn) has emerged as an accelerator for nitrogen metabolism. However, the bioactivity of manganese is limited by the restricted contact between microbes and manganese minerals in the solid phase and by the toxicity of manganese to microbes. To enhance the bioactivity of solid-phase manganese, biomineralized manganese oxide (MnOx) modified by Lactobacillus was introduced. Nitrogen removal performance have confirmed the effective role of biomineralized MnOx in accelerating the removal of total inorganic nitrogen (TIN). Metagenomic analysis has confirmed the enhancement of the nitrogen metabolic pathway and microbial extracellular electron transfer (MEET) in biomineralized MnOx treatment group (BIOA group). Additionally, the enrichment of manganese oxidation and denitrification genus indicates a coupling between nitrogen metabolism and manganese metabolism. One point of views is that biomineralized MnOx-mediated nitrogen transformation processes could serve as a substitute for traditional nitrogen removal processes.

Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.

CD47 blockade reduces ischemia/reperfusion injury in murine heart transplantation and improves donor heart preservation.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts. METHODS: We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h. RESULTS: At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers. CONCLUSION: The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.

Plastron effect enhanced electrochemical CO2 reduction activity over hydrophobic three-dimensional nanoporous silver.

The electrochemical reduction of CO2 on catalyst surfaces is hindered by the inefficient mass transfer of CO2 in aqueous solutions. In this study, we employed an electrochemical reduction approach to fabricate a hydrophobic three-dimensional nanoporous silver catalyst with a plastron effect, aiming to enhance the CO2 diffusion. The resulting catalyst exhibited an exceptional performance with the FECO peaking at 95% at -0.65 V (vs. RHE) and demonstrated remarkable stability during continuous electrolysis for 48 hours. Control experiments, together with Tafel analysis, EIS measurements, and contact angle results, confirmed that the notable enhancement of performance was attributed to the hydrophobic porous structure that facilitated efficient storage and rapid mass transfer of low-solubility CO2 gas reactants.

Circular RNA Expression of Peripheral Blood Mononuclear Cells Associated with Risk of Acute Exacerbation in Smoking Chronic Obstructive Pulmonary Disease.

Purpose: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P<0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P<0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P<0.0001) as well as the year after (r=0.72, P<0.0001). AUC: 0.79, 95% CI: 0.1210-0.3209, P<0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: -0.1972--0.0739 (P <0.0001). Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.

ECM stiffness affects cargo sorting into MSC-EVs to regulate their secretion and uptake behaviors.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered extensive attention as natural product-based nanomedicines and potential drug delivery vehicles. However, the specific mechanism for regulating MSC-EVs secretion and delivery remains unclear. Here, we demonstrate that extracellular matrix (ECM) stiffness regulates the secretion and delivery of EVs by affecting MSCs' cargo sorting mechanically. Using multi-omics analysis, we found that a decrease in ECM stiffness impeded the sorting of vesicular transport-related proteins and autophagy-related lipids into MSC-EVs, impairing their secretion and subsequent uptake by macrophages. Hence, MSC-EVs with different secretion and uptake behaviors can be produced by changing the stiffness of culture substrates. This study provides new insights into MSC-EV biology and establishes a connection between MSC-EV behaviors and ECM from a biophysical perspective, providing a basis for the rational design of biomedical materials.