Electro-Osmotic Flow and Mass Transfer through a Rough Microchannel with a Modulated Charged Surface.

In this paper, we investigate the electro-osmotic flow (EOF) and mass transfer of a Newtonian fluid propelled by a pressure gradient and alternating current (AC) electric field in a parallel microchannel with sinusoidal roughness and modulated charged surfaces. The two-wall roughness is described by in-phase or out-of-phase sine functions with a small amplitude δ. By employing the method of perturbation expansion, the semi-analytical solutions of the Poisson-Boltzmann (P-B) equation based on the Debye-Hückel approximation and the modified Navier-Stokes (N-S) equation are obtained. The numerical solution of the concentration equation is obtained by the finite difference method. The effects of sinusoidal roughness, modulated charged surface, and the AC electric field on the potential field, velocity field, and concentration field are discussed. Under the influence of the modulated charged surface and sinusoidal roughness, vortices are generated. The velocity oscillates due to the effect of the AC electric field. The results indicate that solute diffusion becomes enhanced when the oscillation Reynolds number is below a specific critical value, and it slows down when the oscillation Reynolds number exceeds this critical value.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Substrate Characterization for Hydrolysis of Multiple Types of Aromatic Esters by Promiscuous Aminopeptidases.

Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.

Distribution and spread of tigecycline resistance gene tet(X4) in Escherichia coli from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.

Global Trends of Antibiotic Resistance Genes in Staphylococcus aureus: A Comprehensive Genomic Analysis.

Staphylococcus aureus (S. aureus) is a pathogen capable of causing severe diseases and exhibiting resistance to multiple antibiotics. However, there is a significant lack of comprehensive research on the global prevalence of its antibiotic resistance genes (ARGs). This study provided a comprehensive analysis of ARGs in S. aureus, using 113,842 S. aureus genome sequences from the National Center for Biotechnology Information database. The results revealed that a significant majority (84%) of these genomes harbored at least one ARG, with a total of 389,464 ARG sequences identified across 19 major types and 103 subtypes. These ARGs exhibited varied abundances and diversities, linked primarily to clinical cases worldwide. ARGs for fluoroquinolones, multidrug resistance, bacitracin, tetracyclines, beta-lactams, and aminoglycosides were notably abundant, ranging from 3.16 × 10-5 to 1.49 copies of ARG per million bp. Variations in the abundance and diversity of ARGs were observed between countries, with middle- and low-income countries showing higher gene abundance but lower diversity compared with high-income countries. Temporal analysis over 30 years showed a fluctuating decline in ARG abundance alongside an increase in diversity, suggesting evolving resistance mechanisms. The study also explored the role of mobile genetic elements in ARG dissemination, finding a substantial proportion of ARG subtypes associated with plasmids and insertion sequence elements, indicating their potential for spread across borders. The global distribution of mobile ARGs was further analyzed, revealing the extensive reach of certain ARGs across countries. This research provides valuable insights into the prevalence and dissemination of antibiotic resistance in S. aureus on a global scale, aiding in the development of effective monitoring and control strategies to combat ARGs in S. aureus and other pathogens.

Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model.

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG-E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1ß, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

A Stable Site-Isolated Mono(phosphine)-Rhodium Catalyst on a Metal-Organic Layer for Highly Efficient Hydrogenation Reactions.

Phosphine-ligated transition metal complexes play a pivotal role in modern catalysis, but our understanding of the impact of ligand counts on the catalysis performance of the metal center is limited. Here we report the synthesis of a low-coordinate mono(phosphine)-Rh catalyst on a metal-organic layer (MOL), P-MOL●Rh, and its applications in the hydrogenation of mono-, di-, and tri-substituted alkenes as well as aryl nitriles with turnover numbers (TONs) of up to 390000. Mechanistic investigations and density functional theory calculations revealed the lowering of reaction energy barriers by the low steric hindrance of site-isolated mono(phosphine)-Rh sites on the MOL to provide superior catalytic activity over homogeneous Rh catalysts. The MOL also prevents catalyst deactivation to enable recycle and reuse of P-MOL●Rh in catalytic hydrogenation reactions.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

A Benzothiadiazole-Based Zn(II) Metal-Organic Framework with Visual Turn-On Sensing for Anthrax Biomarker and Theoretical Calculation.

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.

Losartan May Not Prevent Vestibular Schwannoma Growth or Related Hearing Loss During Observation.

OBJECTIVE: To evaluate the impact of losartan on vestibular schwannoma (VS) growth and related hearing loss during observation. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Sporadic VS patients undergoing initial observation with at least two magnetic resonance imaging and audiologic examinations. INTERVENTION: Losartan. MAIN OUTCOME MEASURES: Endpoints included VS growth, quantitative audiologic changes, survival free of tumor growth, and survival free of nonserviceable hearing. Patient characteristics and endpoints were compared by losartan use. RESULTS: Seventy-nine patients were included, of which 33% were taking losartan. Tumor growth was observed in 50% of patients in the losartan group and 36% in the non-losartan group (p = 0.329). Survival analysis failed to show a significant difference in the hazard rate of VS growth between groups (hazard ratio, 1.38; 95% confidence interval, 0.70-2.70; p = 0.346). Throughout observation, mean decreases in normalized pure-tone average were 5.5 and 9.3 dB in the losartan and non-losartan groups, respectively (p = 0.908). Mean decreases in normalized word recognition score were 11.0 and 16.6% in the losartan and non-losartan groups, respectively (p = 0.757). Nonserviceable hearing developed in 19% of patients in the losartan group and 28% in the non-losartan group (p = 0.734). Survival analysis did not demonstrate a significant difference in the hazard rate of developing nonserviceable hearing between groups (hazard ratio, 1.71; 95% confidence interval, 0.56-5.21; p = 0.337). CONCLUSIONS: Losartan use may not reduce the risk of VS growth or hearing loss during observation. A randomized trial would be ideal to further identify the true effect on growth and hearing.

Caregivers' experiences in helping individuals with severe and enduring mental health challenges integrate into the community: A qualitative descriptive study in Singapore.

WHAT IS KNOWN ABOUT THE SUBJECT: Individuals with severe and enduring mental health challenges continued to consume mental health services for an average of 13 years as they needed multiple acute psychiatric admissions due to the challenges they experienced in their everyday activities. As caregivers of individuals with severe and enduring mental health challenges, they often bear the brunt of caregiving through their assistance with activities of daily living (ADL), providing emotional support and ensuring medication compliance for their loved ones. When caring for their loved ones, caregivers often reported psychological stress, social isolation and emotional exhaustion due to stressors such as uncertainty of the future, the lack of support from professional services and the isolation from their own social network and support mechanism. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Insights from this study revealed that caregivers for individuals with severe and enduring mental health challenges went through a lonely and exhausting journey fraught with psychological, physical, social and financial challenges, echoing the caregiving needs and the prevalence of the caregiver burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Insights shared by the caregivers demonstrated the need for a centralised point of contact to navigate Singapore's fragmented mental healthcare sector. Peer-support groups should be further promoted because they offer the benefits of information exchange, mutual support and a sense of empowerment and hopefulness, which may help ease the caregiver burden. Life skills training, such as teaching how to communicate empathetically with family members, resolve conflicts using open communication, maintain a structured daily routine and solve pragmatic problems in daily life, is more critical for individuals with severe and enduring mental health challenges. This will help them learn how to manage their well-being, live independently, and stabilise their conditions. Lastly, public awareness campaigns should honour caregivers by highlighting their strength, resilience, and dedication. The state can provide financial assistance in the form of tax relief for their income per annum or caregiver allowance to alleviate the financial stress that caregivers are facing. ABSTRACT: Introduction The progressive deinstitutionalisation of mental healthcare has increasingly shifted care responsibilities from healthcare professionals to family caregivers for individuals with severe mental illness. Caregivers must balance many obligations, which often compromise their overall health and well-being, while helping their loved ones integrate into the community. Aim To identify and understand caregivers' needs and challenges as they help individuals with severe and enduring mental health challenges integrate into the community. Methods This study used a descriptive qualitative approach to explore the experiences and challenges of caregivers for individuals with severe and enduring mental health challenges when integrating back into the community. A semi-structured guide was used during the video-conferencing interviews conducted between December 2021 and November 2022. This study was reported according to the 32-item Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Findings Fourteen caregivers were individually interviewed by the primary author. Most caregivers were female, with an average of 15 years of experience caring for their loved ones. Using Braun and Clark's six-phase thematic framework, we inductively generate the themes and subthemes from the data. The two themes were (i) challenges (whose subthemes included personal challenges in caregiving, the lack of awareness, and stigma and employment) and (ii) support (whose subthemes included the importance of socialisation for individuals with mental health conditions, existing avenues of support and potential areas for support). Discussion Our findings informed the contemporary needs of caregivers caring for individuals with severe and enduring mental health challenges integrating into the community. Like the global challenges for people with mental health issues, psychosocial support and other supplementary support are still common themes in mental health settings. The findings further specifically highlighted the importance of accessible points of contact as resources and employment-enabling and sustaining initiatives to help manage caregivers' emotional and system challenges, which addresses the gaps identified in the findings. Caregivers' peer-support groups, life skills training and public mental health awareness are also necessitated by the caregivers' voices. Implications for Practice Priority areas include having a centralised point of contact within the community for caregivers. Government or not-for-profit organisations can take the lead by initiating employment-enabling initiatives for individuals with severe and enduring mental health challenges and their caregivers.

Theoretical Study on the O-H Fracture of Methanol on PtnCu4-n (n = 1, 2, 3) Catalysts with Different Coverages.

Direct methanol fuel cells (DMFCs) have attracted increasing attention as a very promising and important energy source. In this paper, density functional theory (DFT) is used to study the structure and O-H fracture mechanism of methanol adsorption on PtnCu4-n (111) (n = 1, 2, 3) binary metal catalyst surfaces under different coverages. By comparing the adsorption energy and dehydrogenation energy barriers of methanol, it is found that the adsorption strength and dehydrogenation energy barriers of methanol on Pt and Cu sites decreased with increasing coverage. At the same Pt and Cu ratio, methanol is more easily adsorbed on Cu sites. When Pt/Cu = 3:1 and 1:3, the PtCu binary catalyst has a significant impact on the energy barrier of breaking the O-H bond in methanol with the increase of coverage. Especially when Pt/Cu = 1:3 and the coverage is 1/4 ML, the energy barriers of O-H bond breaking in methanol on Pt and Cu sites are 0.63 and 0.61 eV, respectively, which are lower than that on pure Pt. It means that the Cu sites played a very important role in reducing the O-H fracture energy barrier of methanol. When Pt/Cu = 1:1, the change in the dehydrogenation energy barrier of methanol on Pt sites and Cu sites is not significant, indicating that the coverage has little effect on it.

Phytohabitans maris sp. nov., isolated from marine sediment.

A novel actinobacterium, strain ZYX-F-186T, was isolated from marine sediment sampled on Yongxing Island, Hainan Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain ZYX-F-186T belongs to the genus Phytohabitans, with high similarity to Phytohabitans kaempferiae KK1-3T (98.3 %), Phytohabitans rumicis K11-0047T (98.1 %), Phytohabitans flavus K09-0627T (98.1 %), Phytohabitans houttuyneae K11-0057T (97.9 %), Phytohabitans suffuscus K07-0523T (97.7 %), and Phytohabitans aurantiacus RD004123T (97.7 %). Phylogenetic analysis of 16S rRNA gene sequences showed that the strain formed a single subclade in the genus Phytohabitans. The novel isolate contained meso-diaminopimelic acid, d-glutamic acid, glycine, d-alanine, and l-lysine in the cell wall. The whole-cell sugars were xylose, arabinose, ribose, and rhamnose. The predominant menaquinones were MK-9(H8), MK-9(H6), and MK-9(H4). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylglycerol, and an unknown phospholipid. The major fatty acids (>5 %) were iso-C16 : 0, anteiso-C17 : 0, and iso-C18 : 0. Genome sequencing showed a DNA G+C content of 71.9 mol%. Low average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values demonstrated that strain ZYX-F-186T could be readily distinguished from its closely related species. Based on its phylogenetic, chemotaxonomic, and physiological characteristics, strain ZYX-F-186T represents a novel species of the genus Phytohabitans, for which the name Phytohabitans maris sp. nov. is proposed. The type strain is ZYX-F-186T (=CGMCC 4.8025T=CCTCC AA 2023025T=JCM 36507T).

Social media use and its impact on adult's mental health and well-being: A scoping review.

BACKGROUND: Social media use has grown in importance and prevalence, with its estimated number of users at 4.9 billion worldwide. Social media use research has revealed positive and negative impacts on users' mental health and well-being. However, such impacts among adults have not been examined in any reviews. METHODS: A scoping review was conducted based on the framework by Arksey and O'Malley and reported based on the PRISMA-ScR guidelines. Eight databases were searched from 2005 to December 2021. Articles were included after being reviewed by three independent teams, with discrepancies resolved through consensus with the senior author. Publication-related information (i.e., authors, year of publication, aims, study population, methodology, interventions, comparisons, outcome measures and key findings) were extracted from each study. Thematic analysis was conducted to answer the research questions. RESULTS: Among the 114 eligible articles, young adults (69.6%) represented the main age group. Most studies (78.6%) focused on the negative impacts of social media use on mental health and well-being, with nearly a third (32.1%) assessing such impacts on depression. Notably, this scoping review found that more than three-quarters (78.6%) of the included studies revealed that excessive and passive social media use would increase depression, anxiety, mood, and loneliness. Nevertheless, a third (33.0%) also reported positive impacts, where positive and purposeful use of social media would contribute to improvements in mental health and well-being, such as increased perceived social support and enjoyment. LINKING EVIDENCE TO ACTION: This review has provided an overview of the existing knowledge on how social media use would affect adults and identified areas of research that merit investigations in future studies. More attention should be given to maximizing the positive impacts of social media use on mental health and well-being among adults.

Clinical Presentations and Intense FDG-avidity in Pulmonary Angiomatoid Fibrous Histiocytoma with Potential Diagnostic Pitfalls: A Case Report and Literature Review.

INTRODUCTION: Angiomatoid fibrous histiocytoma (AFH) is a borderline tumor usually affecting the the children or young adults. 18F-Fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) investigations of pulmonary AFH are rare, and there are currently no reports of intense FDG uptake in AFH. CASE REPORT: We report an AFH that occurred in the lung of a 57-year-old woman. She presented with paroxysmal cough and occasional bloodshot sputum. 18FFDG PET/CT revealed a right parahilar nodule with intense FDG-avidity, middle lobe atelectasis, and several bilateral axillary lymph nodes with mild hypermetabolic activity. This patient underwent a right middle lobe lobectomy via video-assisted thoracoscopy. Histopathologically, the diagnosis was pulmonary AFH. She had an uneventful postoperative course, and the bilateral axillary lymph nodes regressed during postoperative follow-up. CONCLUSIONS: The clinical presentation and image findings of patients with primary pulmonary AFH may be potential diagnosis pitfalls. The diagnosis of lymph nodes or distant metastases should be approached with caution. To avoid misdiagnosis, biopsy with histological examination and immunohistochemichal staining should be performed as early as possible.

Cage-rearranged and cage-intact syntheses of azido-functionalized larger T10 and T12 POSSs.

Herein, we investigate the product type and distribution during the synthesis of azido-functionalized larger polyhedral oligomeric silsesquioxanes (POSSs) using 3-chloropropyl- and chloromethyldimethylsilylethyl-functionalized T8, T10, and T12 POSSs as precursors. Our findings indicate that cage rearrangement occurs for the 3-chloropropyl-functionalized POSS cages with a stability order of T12 > T10 > T8, while the chloromethyldimethylsilylethyl-functionalized POSS cages remain structurally intact after the nucleophilic substitution.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Balanced opioid-free anesthesia with lidocaine and esketamine versus balanced anesthesia with sufentanil for gynecological endoscopic surgery: a randomized controlled trial.

In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 µg/kg) and saline, followed by sufentanil (0.1 µg/kg∙h) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kg∙h) and lidocaine (1.5 mg/kg∙h). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06-1.58) and 1.09 (0.70) (95% CI 0.87-1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was - 0.23 (95% CI - 0.58 - 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.