Which strategy is better for lung transplantation: Cardiopulmonary bypass or extracorporeal membrane oxygenation?

Background: In lung transplantation surgery, extracorporeal life support (ECLS) is essential for safety. Various support methods, including cardiopulmonary bypass (CPB) and off-pump techniques, are used, with extracorporeal membrane oxygenation (ECMO) gaining prominence. However, consensus on the best support strategy is lacking.Purpose: This article reviews risks, benefits, and outcomes of different support strategies in lung transplantation. By consolidating knowledge, it aims to clarify selecting the most appropriate ECLS modality.Research Design: A comprehensive literature review examined CPB, off-pump techniques, and ECMO outcomes in lung transplantation, including surgical results and complications.Study Sample: Studies, including clinical trials and observational research, focused on ECLS in lung transplantation, both retrospective and prospective, providing a broad evidence base.Data Collection and/or Analysis: Selected studies were analyzed for surgical outcomes, complications, and survival rates associated with CPB, off-pump techniques, and ECMO to assess safety and effectiveness.Results: Off-pump techniques are preferred, with ECMO increasingly vital as a bridge to transplant, overshadowing CPB. However, ECMO entails hidden risks and higher costs. While safer than CPB, optimizing ECMO postoperative use and monitoring is crucial for success.Conclusions: Off-pump techniques are standard, but ECMO's role is expanding. Despite advantages, careful ECMO management is crucial due to hidden risks and costs. Future research should focus on refining ECMO use and monitoring to improve outcomes, emphasizing individualized approaches for LT recipients.

IgLON5 autoimmunity in a patient with Creutzfeldt-Jakob disease: case report and review of literature.

Objective: We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt-Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF. Case report: A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14-3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein. Conclusion: IgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.

Yield-related quantitative trait loci identification and lint percentage hereditary dissection under salt stress in upland cotton.

Salinity is frequently mentioned as a major constraint in worldwide agricultural production. Lint percentage (LP) is a crucial yield-component in cotton lint production. While the genetic factors affect cotton yield in saline soils are still unclear. Here, we employed a recombinant inbred line population in upland cotton (Gossypium hirsutum L.) and investigated the effects of salt stress on five yield and yield component traits, including seed cotton yield per plant, lint yield per plant, boll number per plant, boll weight, and LP. Between three datasets of salt stress (E1), normal growth (E2), and the difference values dataset of salt stress and normal conditions (D-value), 87, 82, and 55 quantitative trait loci (QTL) were detectable, respectively. In total, five QTL (qLY-Chr6-2, qBNP-Chr4-1, qBNP-Chr12-1, qBNP-Chr15-5, qLP-Chr19-2) detected in both in E1 and D-value were salt related QTL, and three stable QTL (qLP-Chr5-3, qLP-Chr13-1, qBW-Chr5-5) were detected both in E1 and E2 across 3 years. Silencing of nine genes within a stable QTL (qLP-Chr5-3) highly expressed in fiber developmental stages increased LP and decreased fiber length (FL), indicating that multiple minor-effect genes clustered on Chromosome 5 regulate LP and FL. Additionally, the difference in LP caused by Gh_A05G3226 is mainly in transcription level rather than in the sequence difference. Moreover, silencing of salt related gene (GhDAAT) within qBNP-Chr4-1 decreased salt tolerance in cotton. Our findings shed light on the regulatory mechanisms underlining cotton salt tolerance and fiber initiation.

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells.

The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.

Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti-Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus.

Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel are investigated using single-cell RNA sequencing. HAS2@DexP-Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP-Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.

Phosphorylation of G3BP1 is involved in the regulation of PDCoV-induced inflammatory response.

Stress granules (SGs), the main component is GTPase-activating protein-binding protein 1 (G3BP1), which are assembled during viral infection and function to sequester host and viral mRNAs and proteins, are part of the antiviral responses. In this study, we found that porcine deltacoronavirus (PDCoV) infection induced stable formation of robust SGs in cells through a PERK (protein kinase R-like endoplasmic reticulum kinase)-dependent mechanism. Overexpression of SGs marker proteins G3BP1 significantly reduced PDCoV replication in vitro, while inhibition of endogenous G3BP1 enhanced PDCoV replication. Moreover, PDCoV infected LLC-PK1 cells raise the phosphorylation level of G3BP1. By overexpression of the G3BP1 phosphorylated protein or the G3BP1 dephosphorylated protein, we found that phosphorylation of G3BP1 is involved in the regulation of PDCoV-induced inflammatory response. Taken together, our study presents a vital aspect of the host innate response to invading pathogens and reveals attractive host targets for antiviral target.

Methodologic Quality and Pharmacotherapy Recommendations for Patient Blood Management Guidelines for Cardiac Surgery on Cardiopulmonary Bypass.

Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.

Functional identification of bacterial spermine, thermospermine, norspermine, norspermidine, spermidine, and N1-aminopropylagmatine synthases.

Spermine synthase is an aminopropyltransferase that adds an aminopropyl group to the essential polyamine spermidine to form tetraamine spermine, needed for normal human neural development, plant salt and drought resistance, and yeast CoA biosynthesis. We functionally identify for the first time bacterial spermine synthases, derived from phyla Bacillota, Rhodothermota, Thermodesulfobacteriota, Nitrospirota, Deinococcota and Pseudomonadota. We also identify bacterial aminopropyltransferases that synthesize the spermine same mass isomer thermospermine, from phyla Cyanobacteriota, Thermodesulfobacteriota, Nitrospirota, Dictyoglomota, Armatimonadota and Pseudomonadota, including the human opportunistic pathogen Pseudomonas aeruginosa. Most of these bacterial synthases were capable of synthesizing spermine or thermospermine from the diamine putrescine, and so possess also spermidine synthase activity. We found that most thermospermine synthases could synthesize tetraamine norspermine from triamine norspermidine, i.e., they are potential norspermine synthases. This finding could explain the enigmatic source of norspermine in bacteria. Some of the thermospermine synthases could synthesize norspermidine from diamine 1,3-diaminopropane, demonstrating that they are potential norspermidine synthases. Of 18 bacterial spermidine synthases identified, 17 were able to aminopropylate agmatine to form N1-aminopropylagmatine, including the spermidine synthase of Bacillus subtilis, a species known to be devoid of putrescine. This suggests that the N1-aminopropylagmatine pathway for spermidine biosynthesis, which bypasses putrescine, may be far more widespread than realized and may be the default pathway for spermidine biosynthesis in species encoding L-arginine decarboxylase for agmatine production. Some thermospermine synthases were able to aminopropylate N1-aminopropylagmatine to form N12-guanidinothermospermine. Our study reveals an unsuspected diversification of bacterial polyamine biosynthesis, and suggests a more prominent role for agmatine.

Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Artificial kagome lattices of Shockley surface states patterned by halogen hydrogen-bonded organic frameworks.

Artificial electronic kagome lattices may emerge from electronic potential landscapes using customized structures with exotic supersymmetries, benefiting from the confinement of Shockley surface-state electrons on coinage metals, which offers a flexible approach to realizing intriguing quantum phases of matter that are highly desired but scarce in available kagome materials. Here, we devise a general strategy to construct varieties of electronic kagome lattices by utilizing the on-surface synthesis of halogen hydrogen-bonded organic frameworks (XHOFs). As a proof of concept, we demonstrate three XHOFs on Ag(111) and Au(111) surfaces, which correspondingly deliver regular, breathing, and chiral breathing diatomic-kagome lattices with patterned potential landscapes, showing evident topological edge states at the interfaces. The combination of scanning tunnelling microscopy and noncontact atomic force microscopy, complemented by density functional theory and tight-binding calculations, directly substantiates our method as a reliable and effective way to achieve electronic kagome lattices for engineering quantum states.

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Background: Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. Materials and methods: We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. Results: The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). Conclusion: FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci.

Backgrounds: Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods: A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results: Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis (p < 5 × 10-5). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion: We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients' prognosis and informing treatment options.

Tuning interfacial oxygen vacancy level of bismuth oxybromide to enhance photocatalytic degradation of bisphenol A.

Oxygen vacancies (OVs) have garnered significant interest for their role as active sites, enhancing the catalytic efficiency of various catalysts. Despite their widespread application in environmental purification processes, the generation of OVs conventionally depends on high-temperature conditions and strong reducing agents for the extraction of surface partial oxygen atoms from catalysts. In this work, bismuth oxybromide (BiOBr) nanosheets with varying levels of OVs were synthesized via a simple and effective solvothermal method. This novel method affords precise control over the conduction band (CB) and valence band (VB) positions of BiOBr. The presence of different OVs exhibited varying photocatalytic efficiencies in the degradation of bisphenol A (BPA) under visible light irradiation, with higher levels of OVs resulting in superior photocatalytic performance. Furthermore, radical scavenger experiments demonstrated that superoxide oxides (O2•-) and holes (h+) were the primary reactive oxygen species for BPA degradation. Additionally, BiOBr-OVs exhibited excellent anti-interference and stability in water matrices containing diverse inorganic anions and organic compounds. This work provides a simple and effective approach for the fine-regulating of catalysts through interfacial defect engineering, paving the way for their practical application in environmental decontamination.

Integrative transcriptomic and metabolomic analyses reveals the toxicity and mechanistic insights of bioformulated chitosan nanoparticles against Magnaporthe oryzae.

Rice blast, an extremely destructive disease caused by the filamentous fungal pathogen Magnaporthe oryzae, poses a global threat to the production of rice (Oryza sativa L.). The emerging trend of reducing dependence on chemical fungicides for crop protection has increased interest in exploring bioformulated nanomaterials as a sustainable alternative antimicrobial strategy for effectively managing plant diseases. Herein, we used physiomorphological, transcriptomic, and metabolomic methods to investigate the toxicity and molecular action mechanisms of moringa-chitosan nanoparticles (M-CNPs) against M. oryzae. Our results demonstrate that M-CNPs exhibit direct antifungal properties by impeding the growth and conidia formation of M. oryzae in a concentration-dependent manner. Propidium iodide staining indicated concentration-dependent significant apoptosis (91.33%) in the fungus. Ultrastructural observations revealed complete structural damage in fungal cells treated with 200 mg/L M-CNPs, including disruption of the cell wall and destruction of internal organelles. Transcriptomic and metabolomic analyses revealed the intricate mechanism underlying the toxicity of M-CNPs against M. oryzae. The transcriptomics data indicated that exposure to M-CNPs disrupted various processes integral to cell membrane biosynthesis, aflatoxin biosynthesis, transcriptional regulation, and nuclear integrity in M. oryzae., emphasizing the interaction between M-CNPs and fungal cells. Similarly, metabolomic profiling demonstrated that exposure to M-CNPs significantly altered the levels of several key metabolites involved in the integral components of metabolic pathways, microbial metabolism, histidine metabolism, citrate cycle, and lipid and protein metabolism in M. oryzae. Overall, these findings demonstrated the potent antifungal action of M-CNPs, with a remarkable impact at the physiological and molecular level, culminating in substantial apoptotic-like fungal cell death. This research provides a novel perspective on investigating bioformulated nanomaterials as antifungal agents for plant disease control.

Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination.

Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis. Genetic analysis indicated that these viruses belonged to a single genotype previously detected in poultry. Antigenic analysis indicated that 12 of the 16 viruses were antigenically close to the H7-Re4 vaccine virus that has been used since January 2022, and the other four viruses showed reduced reactivity with the vaccine. Animal studies indicated that all 16 viruses were nonlethal in mice, and four of six viruses showed reduced virulence in chickens upon intranasally inoculation. Importantly, the H7N9 viruses detected in this study exclusively bound to the avian-type receptors, having lost the capacity to bind to human-type receptors. Our study shows that vaccination slows the evolution of H7N9 virus by preventing its reassortment with other viruses and eliminates a harmful characteristic of H7N9 virus, namely its ability to bind to human-type receptors.

Design, Synthesis, and Biological Evaluation of ß-Trifluoroethoxydimethyl Selenides as Potent Antiosteoporosis Agents.

An efficient protocol for the synthesis of ß-trifluoroethoxydimethyl selenides was achieved under mild reaction conditions, and 39 compounds were prepared. All compounds were evaluated for their abilities to inhibit RANKL-induced osteoclastogenesis, compound 4aa exhibited the most potent activity. Further investigations revealed that 4aa could inhibit F-actin ring generation, bone resorption, and osteoclast-specific gene expression in vitro. Western blot analyses demonstrated that compound 4aa abrogated the RANKL-induced mitogen-activated protein kinase and NF-kB-signaling pathways. In addition, 4aa also displayed a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. In vivo experiments revealed that compound 4aa significantly ameliorated bone loss in an ovariectomized (OVX) mice model. Furthermore, the surface plasmon resonance experiment results revealed that 4aa probably bound to RANKL. Collectively, the above-mentioned findings suggested that compound 4aa as a potential RANKL inhibitor averted OVX-triggered osteoporosis by regulating the inhibition of osteoclast differentiation and stimulation of osteoblast differentiation.

Nitrogen-Based Gas Molecule Adsorption on a ReSe2 Monolayer via Single-Atom Doping: A First-Principles Study.

Two-dimensional materials have shown immense promise for gas-sensing applications due to their remarkable surface-to-volume ratios and tunable chemical properties. However, despite their potential, the utilization of ReSe2 as a gas-sensing material for nitrogen-containing molecules, including NO2, NO, and NH3, has remained unexplored. The choice of doping atoms in ReSe2 plays a pivotal role in enhancing the gas adsorption and gas-sensing capabilities. Herein, the adsorption properties of nitrogen-containing gas molecules on metal and non-metal single-atom (Au, Pt, Ni, P, and S)-doped ReSe2 monolayers have been evaluated systematically via ab initio calculations based on density functional theory. The findings strongly suggest that intrinsic ReSe2 has better selectivity toward NO2 than toward NO and NH3. Moreover, our results provide compelling evidence that all of the dopants, with the exception of S, significantly enhance both the adsorption strength and charge transfer between ReSe2 and the investigated molecules. Notably, P-decorated ReSe2 showed the highest adsorption energy for NO2 and NO (-1.93 and -1.52 eV, respectively) with charge transfer above 0.5e, while Ni-decorated ReSe2 exhibited the highest adsorption energy for NH3 (-0.76 eV). In addition, on the basis of transition theory, we found that only Au-ReSe2 and Ni-ReSe2 can serve as reusable chemiresisitve gas sensors for reliable detection of NO and NH3, respectively. Hence, our findings indicate that gas-sensing applications can be significantly improved by utilizing a single-atom-doped ReSe2 monolayer.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.