ABSTRACT
Catalysts are the primary facilitator in many dynamic processes. Therefore, a thorough understanding of these processes has vast implications for a myriad of energy systems. The scanning/transmission electron microscope (S/TEM) is a powerful tool not only for atomic-scale characterization but also in situ catalytic experimentation. Techniques such as liquid and gas phase electron microscopy allow the observation of catalysts in an environment conducive to catalytic reactions. Correlated algorithms can greatly improve microscopy data processing and expand multidimensional data handling. Furthermore, new techniques including 4D-STEM, atomic electron tomography, cryogenic electron microscopy, and monochromated electron energy loss spectroscopy (EELS) push the boundaries of our comprehension of catalyst behavior. In this review, we discuss the existing and emergent techniques for observing catalysts using S/TEM. Challenges and opportunities highlighted aim to inspire and accelerate the use of electron microscopy to further investigate the complex interplay of catalytic systems.
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BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) is prone to cause early recurrent stroke (ERS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels and prevent cardiovascular events. This multicentre, hospital-based prospective cohort study was designed to investigate whether PCSK9 inhibitors would prevent ERS in patients with symptomatic ICAS. METHODS: From 1 October 2020 to 30 September 2022, consecutive patients with acute ischaemic stroke attributed to ICAS admitted within 1 week after onset were enrolled and followed up for 1 month. Patients were divided into two groups, the PCSK9 inhibitors group receiving PCSK9 inhibitors add-on therapy, and the control group receiving statins and/or ezetimibe. The primary outcome was ERS. Cox proportional hazard models and Kaplan-Meier survival curve were used to estimate the association between PCSK9 inhibitors and ERS. RESULTS: At the end of follow-up, the LDL-C levels were further lowered by PCSK9 inhibitors add-on therapy (n=232, from 3.06±1.16 mmol/L to 2.12±1.19 mmol/L) than statins and/or ezetimibe treatment (n=429, from 2.91±1.05 mmol/L to 2.64±0.86 mmol/L, p<0.001). The Kaplan-Meier survival curves showed that PCSK9 inhibitors add-on therapy significantly reduced ERS (5.59%, 24/429, vs 2.16%, 5/232; log-rank test, p=0.044). The multivariate Cox regression analysis revealed that, after adjusting for confounders with a p value less than 0.05 in univariate analysis or of particular importance, the HR was 0.335 (95% CI 0.114 to 0.986, p=0.047), compared with the control group. CONCLUSIONS: In our study, PCSK9 inhibitors add-on therapy further reduced LDL-C levels and ERS in patients with symptomatic ICAS.
Subject(s)
Ezetimibe , Intracranial Arteriosclerosis , PCSK9 Inhibitors , Humans , Male , Female , Intracranial Arteriosclerosis/drug therapy , Intracranial Arteriosclerosis/complications , Middle Aged , Aged , Ezetimibe/therapeutic use , Prospective Studies , Cholesterol, LDL/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Recurrence , Anticholesteremic Agents/therapeutic use , Ischemic Stroke/drug therapy , Ischemic Stroke/complications , Stroke/drug therapy , Secondary PreventionABSTRACT
In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (â3-α-L-fucp(2-SO3-)-1â4-α-L-fucp(2,3-SO3-)-1âsection), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.
Subject(s)
Acetylcholinesterase , Alzheimer Disease , Cholinesterase Inhibitors , Molecular Docking Simulation , Oligosaccharides , Sargassum , Sargassum/chemistry , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/therapeutic use , Mice , Acetylcholinesterase/metabolism , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/isolation & purification , Male , Sulfates/chemistry , Sulfates/pharmacology , Butyrylcholinesterase/metabolism , Maze Learning/drug effects , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Dose-Response Relationship, DrugABSTRACT
The elevation of the low-temperature oxidation activity for Pt/CeO2 catalysts is challenging to meet the increasingly stringent requirements for effectively eliminating carbon monoxide (CO) from automobile exhaust. Although reducing activation is a facile strategy for boosting reactivity, past research has mainly concentrated on applying H2 as the reductant, ignoring the reduction capabilities of CO itself, a prevalent component of automobile exhaust. Herein, atomically dispersed Pt/CeO2 was fabricated and activated by CO, which could lower the 90% conversion temperature (T90) by 256 °C and achieve a 20-fold higher CO consumption rate at 200 °C. The activated Pt/CeO2 catalysts showed exceptional catalytic oxidation activity and robust hydrothermal stability under the simulated working conditions for gasoline or diesel exhausts. Characterization results illustrated that the CO activation triggered the formation of a large portion of Pt0 terrace sites, acting as inherent active sites for CO oxidation. Besides, CO activation weakened the Pt-O-Ce bond strength to generate a surface oxygen vacancy (Vo). It served as the oxygen reservoir to store the dissociated oxygen and convert it into active dioxygen intermediates. Conversely, H2 activation failed to stimulate Vo, but triggered a deactivating transformation of the Pt nanocluster into inactive PtxOy in the presence of oxygen. The present work offers coherent insight into the upsurging effect of CO activation on Pt/CeO2, aiming to set up a valuable avenue in elevating the efficiency of eliminating CO, C3H6, and NH3 from automobile exhaust.
Subject(s)
Carbon Monoxide , Oxidation-Reduction , Catalysis , Carbon Monoxide/chemistry , Vehicle Emissions , Platinum/chemistry , Cerium/chemistryABSTRACT
OBJECTIVES: With the increasing demand and application of lymphocyte subsets detection in clinical laboratories, different single-platform flow cytometer (FCM) systems have been developed. There is an urgent need to establish the reference intervals (RIs) for different single-platform FCMs and transferring them from one FCM system to another provides a much more feasible and convenient approach. This study aimed to explore the transferability of RIs for lymphocyte subsets across different flow cytometry platforms. METHODS: We first conducted the pairwise method comparison across four FCM platforms, including NovoCyte, BriCyteE6, DxFLEX, and FACSCantoII systems. Next, the transferability of RIs of lymphocyte subsets was evaluated. Furthermore, we conducted the RIs transference based on the FACSCantoII system, BriCyteE6 system and DxFLEX system, except for NK cells. The transferred RIs were further verified by calculating the bias (CV) between the established ones. RESULTS: The results of lymphocyte subsets detection based on the NovoCyte, BriCyteE6, DxFLEX, and FACSCantoII systems were comparable and it was feasible to transfer the RIs of lymphocyte subsets detected by the four FCM systems. The RIs of lymphocyte subsets detection using FACSCantoII, DxFLEX, and BriCyteE6 systems were established. Upon transferring the RIs of lymphocyte subsets from the FACSCantoII system to the BriCyteE6 system, and DxFLEX system except for NK cells, the CV between the transferred RIs and the established ones was below 20â¯% for all parameters. CONCLUSIONS: The present study illustrated that the RIs of lymphocyte subsets could be transferred across different flow cytometry systems except for NK cells with different definition strategies.
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BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.
Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Female , Adolescent , Young Adult , Adult , Homosexuality, Male , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , Tenofovir/therapeutic use , Depression/epidemiology , Anti-HIV Agents/therapeutic use , Medication Adherence , Sexual Behavior , Anxiety/epidemiology , China/epidemiologyABSTRACT
BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/mortality , Male , Female , Middle Aged , China/epidemiology , Aged , Risk Factors , Hospitalization/statistics & numerical data , Adult , Prognosis , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Age Factors , Logistic Models , Neutrophils , Blood Urea Nitrogen , L-Lactate Dehydrogenase/bloodABSTRACT
BACKGROUND: To date, no randomized controlled trials have specifically addressed behavior changes after HIV self-testing (HIVST) among transgender women. OBJECTIVE: This study aims to evaluate the effects of HIVST on changes in HIV testing behavior, frequency of condomless sex, and partner numbers among transgender women in China. METHODS: Participants were recruited from 2 Chinese cities using both online and offline methods. Transgender women were randomly assigned to receive an HIVST intervention. Data from the previous 3 months were collected at baseline, 3 months, and 6 months. The primary outcome was the mean change in the number of HIV tests among transgender women during the 6-month follow-up. An intention-to-treat analysis was conducted. The statistical analysis used analysis of covariance and linear mixed-effects models. RESULTS: From February to June 2021, and 255 transgender women were recruited, of which only 36.5% (93/255) had a steady job, and 27.1% (69/255) earned less than US $414.9 of income per month. They were randomly assigned to the intervention (n=127) and control (n=128) groups. At 6 months, the mean number of HIV tests was 2.14 (95% CI 1.80-2.48) in the intervention group and 1.19 (95% CI 0.99-1.40) in the control group (P<.001), with increases of 0.84 (95% CI 0.54-1.14) and 0.11 (95% CI -0.19-0.41) over 6 months, respectively. The net increase was 0.73 (95% CI 0.31-1.15; P<.001), with a similar adjusted result. No significant differences in the frequency of condomless sex or partner numbers were observed between the 2 groups. CONCLUSIONS: HIVST is an effective strategy for enhancing regular HIV testing behavior among transgender women in China. This strategy should be combined with measures to address the financial vulnerability of the transgender women community to reduce subsequent risk behaviors, including condomless sex. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039766; https://www.chictr.org.cn/showproj.html?proj=61402.
Subject(s)
HIV Infections , Self-Testing , Transgender Persons , Humans , Transgender Persons/psychology , Transgender Persons/statistics & numerical data , Female , China , Adult , HIV Infections/diagnosis , HIV Infections/prevention & control , HIV Infections/psychology , Male , Risk Reduction Behavior , Young Adult , HIV Testing/methods , HIV Testing/statistics & numerical dataABSTRACT
A novel compound streptothiomycin F (1), and a new natural product, N-(5-nitropentyl)acetamide (2), were discovered alongside ten previously identified compounds (3-12) through solid fermentation of marine-derived Streptomyces sp. ZS-A31 based on rice. The chemical structures of compounds 1-2 were elucidated using 1D and 2D NMR, as well as HRESIMS data analysis. Evaluation of all isolated compounds for their antibiofilm and antibacterial activities against P. aeruginosa was carried out using microdilution and crystal violet staining methods. Results highlighted the weak potency of the known compounds lumichrome (3) and vanillic acid (7) in inhibiting biofilm formation.
Subject(s)
Anti-Bacterial Agents , Biofilms , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Streptomyces , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Biofilms/drug effects , Biological Products/chemistry , Biological Products/pharmacology , Biological Products/isolation & purification , Biological Products/metabolism , Molecular Structure , Pseudomonas aeruginosa/drug effects , Streptomyces/chemistry , Streptomyces/metabolism , Structure-Activity Relationship , Vanillic Acid/chemistry , Vanillic Acid/metabolismABSTRACT
A novel staurosporine derivate, streptomholyrine A (1), along with 6â known compounds were identified from the rice-based solid fermentation of marine-derived Streptomyces sp. ZS-A121. The planar structure and absolute configuration of streptomholyrine A were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, chemical transformation, ECD and NMR calculations. Screening of all these compounds revealed their cytotoxic activity against HCT-116â cell lines, with IC50 values ranging from 0.012 to 11.67â µM, except for the known 1H-indole-3-hydroxyacetyl, which showed no inhibition activity. Furthermore, streptomholyrine A, along with two known staurosporine derivatives, k252d and staurosporine, exhibited activities against Candida albicans, with MICs of 12.5, 25.0 and 50.0â µg/ml, respectively.
Subject(s)
Actinobacteria , Antineoplastic Agents , Streptomyces , Humans , Staurosporine/pharmacology , Staurosporine/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Streptomyces/chemistry , Antineoplastic Agents/chemistry , Molecular StructureABSTRACT
Two new alpiniamide-type polyketides, alpiniamides H-I (1-2), in addition to four recognized compounds, were discovered in Streptomyces sp. ZSA65 derived from the marine sediments. The planar structure and absolute configuration of alpiniamides H-I were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, Mosher's method and ECD calculations. The antibiofilm and antibacterial activities against P. aeruginosa were evaluated using the microdilution method. Notably, Compound 2 exhibited strong antibiofilm property.
Subject(s)
Polyketides , Streptomyces , Polyketides/pharmacology , Polyketides/chemistry , Streptomyces/chemistry , Anti-Bacterial Agents/pharmacology , Magnetic Resonance Spectroscopy , Biofilms , Molecular StructureABSTRACT
BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.
Subject(s)
HIV Infections , Toll-Like Receptor 7 , Humans , CD47 Antigen , Janus Kinases/metabolism , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/metabolism , Ligands , STAT3 Transcription Factor/metabolism , Interferon-gamma/metabolismABSTRACT
BACKGROUND: The mortality rate of patients with sepsis has been increasing in recent years. Alterations of biomarkers levels during treatment are important in evaluating treatment efficacy and predicting outcomes in sepsis. This meta-analysis investigated the relationship between changes in cytokine levels after treatment compared with those on hospital admission, and their relationship with the prognosis of patients with sepsis. METHODS: From conception until August 4, 2021, a complete literature search of the PubMed, Web of Science, and Cochrane Library electronic databases was done. Observational studies where the outcomes of sepsis patients were divided into non-survivors and survivors and which reported cytokine levels at least before treatment in ICU were included in the current study. Standardized mean difference (SMD) with 95% confidence intervals (CI) values from individual studies were pooled using a random-effects model. Quality assessment, subgroup analysis, publication bias, and sensitivity analyses were all carried out. RESULTS: A total of 2570 patients with sepsis from 25 eligible studies were included, and 14 of them measured the cytokine levels before and after treatment in ICU. Among IL-6, TNF-α, IL-1ß and IL-10 levels, those of IL-6 were significantly lower after treatment in ICU than at baseline in patients with sepsis in the survival group (SMD = -0.69, P < 0.0001), but were comparable in the non-survival group (SMD = -0.99, P = 0.0575). Similarly, post-treatment TNF-α levels were significantly lower than those at baseline only in patients with sepsis in the survival group (SMD = -0.44, P < 0.0001), but not in the non-survival group (SMD =-0.17, P = 0.0842). CONCLUSION: This meta-analysis shows that reduced IL-6 and TNF-α levels after sepsis treatment in ICU may be indicators of better prognosis and survival of patients with sepsis.
Subject(s)
Cytokines , Sepsis , Humans , Tumor Necrosis Factor-alpha , Interleukin-6 , Sepsis/therapy , BiomarkersABSTRACT
Recalcitrant dissolved organic carbon (RDOC) produced by microbial carbon pumps (MCPs) in the ocean is crucial for carbon sequestration and regulating climate change in the history of Earth. However, the importance of microbes on RDOC formation in terrestrial aquatic systems, such as rivers and lakes, remains to be determined. By integrating metagenomic (MG) and metatranscriptomic (MT) sequencing, we defined the microbial communities and their transcriptional activities in both water and silt of a typical karst river, the Lijiang River, in Southwest China. Betaproteobacteria predominated in water, serving as the most prevalent population remodeling components of dissolved organic carbon (DOC). Binning method recovered 45 metagenome-assembled genomes (MAGs) from water and silt. Functional annotation of MAGs showed Proteobacteria was less versatile in degrading complex carbon, though cellulose and chitin utilization genes were widespread in this phylum, whereas Bacteroidetes had high potential for the utilization of macro-molecular organic carbon. Metabolic remodeling revealed that increased shared metabolites within the bacterial community are associated with increased concentration of DOC, highlighting the significance of microbial cooperation during producing and remodeling of carbon components. Beta-oxidation, leucine degradation, and mevalonate (MVA) modules were significantly positively correlated with the concentration of RDOC. Blockage of the leucine degradation pathway in Limnohabitans and UBA4660-related MAGs were associated with decreased RDOC in the karst river, while the Fluviicola-related MAG containing a complete leucine degradation pathway was positively correlated with RDOC concentration. Collectively, our study revealed the linkage between bacteria metabolic processes and carbon sequestration. This provided novel insights into the microbial roles in karst-rivers carbon sink.
Subject(s)
Carbon Sequestration , Rivers , Rivers/chemistry , Dissolved Organic Matter , Leucine/metabolism , Multiomics , Carbon/metabolism , Bacteria/genetics , Bacteria/metabolism , Water/metabolismABSTRACT
BACKGROUNDS: Horner syndrome presents with ipsilateral ptosis, miosis, and anhidrosis due to interruption of the oculosympathetic pathway. Patients with acute ischemic stroke may present with Horner syndrome, which may help locate the lesion. However, the underlying pathways involved in Horner syndrome caused by isolated lenticulostriate ischemic stroke remain unclear. METHODS: We screened consecutive patients with acute ischemic stroke admitted to the Second Affiliated Hospital of Guangzhou Medical University from 1 January 2020 to 31 December 2021, and searched for cases of isolated lenticulostriate strokes presenting with Horner syndrome. Strokes involving the brainstem or hypothalamus, or those caused by carotid dissection or carotid cavernous fistula were excluded based on neuroimaging and cerebrovascular examination. RESULTS: Among the 1706 acute stroke patients, three patients developed temporary or long-term Horner syndrome due to an ipsilateral lenticulostriate ischemic lesion. Diffusion-tensor imaging revealed disruption of an uncrossed pathway from Brodmann areas 3, 1, and 2 through the basal ganglia to the ipsilateral hypothalamus. CONCLUSION: These findings suggest that Horner syndrome may be due to a disruption of an uncrossed cortico-basal ganglia-hypothalamic sympathetic pathway.
Subject(s)
Horner Syndrome , Ischemic Stroke , Stroke , Humans , Horner Syndrome/etiology , Ischemic Stroke/complications , Stroke/complications , Neuroimaging , HypothalamusABSTRACT
INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.
Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Homosexuality, Male , HIV Infections/prevention & control , HIV Infections/drug therapy , Cross-Sectional Studies , Patient Acceptance of Health Care , Anti-HIV Agents/therapeutic useABSTRACT
Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (1-2) and one known 2-methyl-4-(1-glycerol)-furan (3). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound 1 represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs.
Subject(s)
Glycerol , Nocardiopsis , Mice , Animals , Hypolipidemic Agents/therapeutic use , Plant Extracts/chemistry , LipidsABSTRACT
INTRODUCTION: We aimed to investigate the relationship between low-level viremia (LLV) and virological failure (VF), death, and non-AIDS events (NAEs). METHODS: A prospective cohort study of people living with HIV (PLHIV) on antiretroviral therapy (ART) was conducted from 2011-2018 at an HIV clinic in Shenyang, China. The incidence of VF and the mortality and NAEs due to LLV were assessed. Cox proportional hazards regression was performed to investigate risk factors for VF, mortality, and NAEs. RESULTS: In total, 1288 patients, contributing 3915 person-years of follow-up (median follow-up, 2.5 years [interquartile range: 2-4 years]), were enrolled. Thirty-one patients (2.4%) experienced VF, 5 (0.4%) died, and 38 (3.0%) experienced NAEs. The risk of VF was significantly increased among patients with a viral load (VL) of 200-499 copies/mL (adjusted hazard ratio [aHR]: 14.92, 95% confidence interval [CI]: 5.92-37.60) or 500-999 copies/mL (aHR: 13.68, 95% CI: 3.61-51.87), but not among patients with a VL of 50-199 copies/mL (aHR: 3.10, 95% CI: 0.86-11.09). The risk of NAEs was significantly increased among patients with LLV (aHR: 7.33, 95% CI: 3.73-14.42). Compared to no LLV, a VL of 50-199 copies/mL (aHR: 4.11, 95% CI: 1.73-9.74), 200-499 copies/mL (aHR: 18.31, 95% CI: 6.66-50.33), and 500-999 copies/mL (aHR: 21.34, 95% CI: 5.69-80.01) showed higher risk of NAEs. CONCLUSION: Low-level viremia was associated with VF and NAEs. Patients with LLV, especially those with a VL ≥200 copies/mL, may need more frequent VL testing and NAE screening.
Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , HIV-1 , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Humans , Prospective Studies , Viral Load , Viremia/drug therapy , Viremia/epidemiologyABSTRACT
BACKGROUND: Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker of insulin resistance. Elevated TyG index was related to stroke recurrence. This study aimed to explore the associations between TyG index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion. METHODS: From November 1, 2016 to February 28, 2021, consecutive acute ischemic stroke patients admitted within 1 week after onset were screened. The stroke mechanism was determined based on medical history, laboratory examinations, cardiac examinations, vascular examinations and neuroimaging. Nondiabetic patients with small vessel occlusion were enrolled and followed up for 1 year. The primary outcome was ischemic stroke recurrence. Logistic regression and Kaplan-Meier survival curve were used to analyze the association of the TyG index and stroke recurrence. RESULTS: A total of 6100 acute ischemic stroke patients were screened, with 1970 nondiabetic patients with small vessel occlusion included and divided into 4 groups according to the TyG index quartiles (Q1: < 8.20; Q2: 8.20-8.53; Q3: 8.54-8.92; Q4: > 8.92). There were significant differences in age, body mass index, systolic blood pression, diastolic blood pressure, lipid-lowering agents, infarct location, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and stroke recurrence among the 4 groups. In the multi-adjusted models, compared to Q1 of the TyG index, the odds ratio for Q4 of the TyG index for stroke recurrence was 3.100 (1.366-8.019). The Kaplan-Meier survival (ischemic stroke-free) curves by quartiles of the TyG index also showed statistically significant differences (log-rank test, P = 0.004). CONCLUSIONS: Our findings suggested that the TyG index was associated with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion, and it could be a valuable biomarker for assessing the risk of ischemic stroke recurrence in these patients.
Subject(s)
Ischemic Stroke , Stroke , Humans , Triglycerides , Glucose , Blood Glucose , Prospective Studies , Cholesterol, HDL , Biomarkers , Stroke/diagnosis , HospitalsABSTRACT
We have developed a Keggin polyoxometalate (POM)-based ionic-liquid (IL)-immobilizing rhodium single-atom Rh catalyst (MTOA)5 [SiW11 O39 Rh] (MOTA=methyltrioctylammonium cation) that can afford exceptionally high catalytic activity for the hydroformylation of alkenes to produce aldehydes at an ultralow loading of Rh (ca. 3â ppm). For styrene hydroformylation, both the conversion and the yield of the aldehyde can reach almost 99 %, and a TOF as high as 9000â h-1 was obtained without using any phosphine ligand in the reaction process. Further characterization by FTIR, ICP and ESI-MS analysis revealed that the single Rh atom was incorporated in the lacunary POM anions. In particular, the bulky IL cation can play an additional role in stabilizing Rh species and thus prevent aggregation and leaching of Rh species. The IL catalyst was miscible with n-hexane at temperatures; this contributed to exceptionally high activity for hydroformylation even at ultra-low loading of IL catalyst.