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1.
ACS Nano ; 18(33): 22153-22171, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39118372

ABSTRACT

cGAS/STING pathway, which is highly related to tumor hypoxia, is considered as a potential target for remodeling the immunosuppressive microenvironment of solid tumors. Metal ions, such as Mn2+, activate the cGAS/STING pathway, but their efficacy in cancer therapy is limited by insufficient effect on immunogenic tumor cell death of a single ion. Here, we evaluate the association between tumor hypoxia and cGAS/STING inhibition and report a polymetallic-immunotherapy strategy based on large mesoporous trimetal-based nanozyme (AuPdRh) coordinated with Mn2+ (Mn2+@AuPdRh) to activate cGAS/STING signaling for robust adaptive antitumor immunity. Specifically, the inherent CAT-like activity of this polymetallic Mn2+@AuPdRh nanozyme decomposes the endogenous H2O2 into O2 to relieve tumor hypoxia induced suppression of cGAS/STING signaling. Moreover, the Mn2+@AuPdRh nanozyme displays a potent near-infrared-II photothermal effect and strong POD-mimic activity; and the generated hyperthermia and •OH radicals synergistically trigger immunogenic cell death in tumors, releasing abundant dsDNA, while the delivered Mn2+ augments the sensitivity of cGAS to dsDNA and activates the cGAS-STING pathway, thereby triggering downstream immunostimulatory signals to kill primary and distant metastatic tumors. Our study demonstrates the potential of metal-based nanozyme for STING-mediated tumor polymetallic-immunotherapy and may inspire the development of more effective strategies for cancer immunotherapy.


Subject(s)
Immunotherapy , Infrared Rays , Membrane Proteins , Animals , Mice , Membrane Proteins/metabolism , Manganese/chemistry , Manganese/pharmacology , Nucleotidyltransferases/metabolism , Porosity , Signal Transduction/drug effects , Humans , Tumor Hypoxia/drug effects , Gold/chemistry , Gold/pharmacology , Cell Line, Tumor , Palladium/chemistry , Palladium/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Female
2.
J Diabetes ; 16(8): e13598, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39155699

ABSTRACT

BACKGROUND: This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. METHODS: Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. RESULTS: Over the 30-year follow-up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38-2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09-4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19-1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58-2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all-cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. CONCLUSION: IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.


Subject(s)
Cardiovascular Diseases , Glucose Intolerance , Metabolic Syndrome , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/mortality , Female , Glucose Intolerance/complications , Glucose Intolerance/mortality , Male , Middle Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/etiology , Risk Factors , Follow-Up Studies , Aged , Proportional Hazards Models , Blood Glucose/analysis , Blood Glucose/metabolism , Adult
3.
Injury ; 55(11): 111780, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39216413

ABSTRACT

OBJECTIVE: This study aims to evaluate the clinical application efficacy of the ultrasound-guided Joystick technique for percutaneous leverage reduction in conjunction with Kirschner wires and external fixator in the treatment of difficult-to-reduce pediatric Salter-Harris II type proximal humerus fractures. METHODS: A retrospective analysis was conducted on children with Salter-Harris II type proximal humerus fractures, who failed manual closed reduction from January 2018 to March 2022. The group consisted of 7 males and 2 females, aged between 10 and 14 years. The surgical method involved percutaneous leverage reduction using the ultrasound-guided Joystick technique, combined with Kirschner wires and external fixation. Throughout the procedure, ultrasound is used for monitoring, with the fracture condition being determined before surgery. An external support screw is inserted into the distal end of the humerus as an operating lever, along with 3.5 mm Kirschner wire for ultrasound-guided reduction and maintenance of position during the operation. Following fixation with Kirschner wire, a combination external fixator is applied. After fixation is completed, ultrasound is used once more to assess the quality of fracture reduction, followed by verification of the reduction status using a C-arm X-ray machine. RESULTS: All surgeries were successfully completed with a 100 % success rate in resetting. Notably, there were no postoperative complications like nerve or vascular injury, malunion, nonunion, or bone bridge formation in the proximal humeral physis. Three cases experienced minor complications (redness and swelling at the screw sites), which improved with conservative management. The follow-up period ranged from 6 to 18 months, averaging 10.6 months, with fracture clinical healing occurring within 6 to 8 weeks (average 6.3 weeks). The final follow-up revealed excellent functional outcomes, with Neer scores ranging from 90 to 100 (average 96.3 points). CONCLUSION: The ultrasound-guided Joystick technique for percutaneous leverage reduction in conjunction with Kirschner wires and external fixator can effectively treat difficult-to-reduce Salter-Harris II proximal humeral fractures in children, avoiding open reduction and minimizing intraoperative radiation exposure. This approach offers good stability and facilitates early rehabilitation, aligning with the ERAS (Enhanced Recovery After Surgery) concept in fracture management, thus warranting clinical promotion.

4.
PLoS Med ; 21(7): e1004419, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38980837

ABSTRACT

BACKGROUND: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. METHODS AND FINDINGS: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. CONCLUSIONS: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.


Subject(s)
Glucose Intolerance , Humans , Male , Glucose Intolerance/diagnosis , Glucose Intolerance/complications , Female , Middle Aged , Glucose Tolerance Test , China/epidemiology , Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Risk Factors , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Adult
5.
J Colloid Interface Sci ; 675: 302-312, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38972118

ABSTRACT

Electrocatalytic water splitting produces green and pollution-free hydrogen as a clean energy carrier, which can effectively alleviate energy crisis. In this paper, bimetallic and selenium doped cobalt molybdate (Se-CoMoO4) nanosheets with rough surface are resoundingly prepared. The multihole Se-CoMoO4 nanosheets display ultrathin and rectangular architecture with the dimensions of âˆ¼ 3.5 µm and 700 nm for length and width, respectively. The Se-CoMoO4 electrocatalyst shows remarkable water electrolysis activity and stability. The overpotentials of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are 270 and 63.3 mV at 10 mA cm-2, along with low Tafel slopes of 51.6 and 62.0 mV dec-1. Furthermore, the Se-CoMoO4 couple electrolyzer merely requires a cell voltage of 1.48 V to achieve 10 mA cm-2 current density and presents no apparent attenuation for 30 h. This investigation declares that the hybridization of transition bimetallic oxide with nonmetallic adulteration can afford a tactic for the preparation of bifunctional non-precious metal-based electrocatalysts.

6.
Int J Mol Sci ; 25(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39000365

ABSTRACT

Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.


Subject(s)
Aphids , Gene Expression Regulation, Plant , Plant Proteins , Sorghum , Stress, Physiological , Triazoles , Sorghum/genetics , Sorghum/metabolism , Aphids/genetics , Aphids/physiology , Animals , Triazoles/pharmacology , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Oxylipins/metabolism , Oxylipins/pharmacology , Cyclopentanes/metabolism , Cyclopentanes/pharmacology , Arabidopsis/genetics , Promoter Regions, Genetic , Multigene Family , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Phylogeny , Plant Diseases/parasitology , Plant Diseases/genetics , Genome, Plant
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124594, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-38875928

ABSTRACT

A new ratiometric fluorescent sensor (LP) based on bicarboxaminoquinoline was designed and synthesized for sequentially recognizing Zn2+ and PPi. In aqueous solution, LP exhibited the ratiometric fluorescence response towards Zn2+, along with the about 4-folds enhancement of fluorescence quantum yield. Subsequently, the LP-Zn2+ complex displayed the fluorescence recovery upon adding PPi through the displacement strategy. And the LODs of LP and its Zn2+ complex for sensing Zn2+ and PPi were found to be 15 nM and 5.5 nM, respectively. Notably, the reversibility of LP for sequentially sensing Zn2+ and PPi had been employed to construct the INHIBIT logic gate. Moreover, LP and its Zn2+ complex had been successfully utilized for the detection of Zn2+ and PPi in two real water samples and cells imaging.

8.
J Sci Food Agric ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899487

ABSTRACT

BACKGROUND: Walnut protein (WP) is recognized as a valuable plant protein. However, the poor solubility and functional properties limit its application in the food industry. It is a great requirement to improve the physicochemical properties of WP. RESULTS: Following a 90 min restricted enzymatic hydrolysis period, the solubility of WP significantly increased from 3.24% to 54.54%, with the majority of WP hydrolysates (WPHs) possessing a molecular weight exceeding 50 kDa. Circular dichroism spectra showed that post-hydrolysis, the structure of the protein became more flexible, while the hydrolysis time did not significantly alter the protein's secondary structure. After hydrolysis, WP's surface hydrophobicity significantly increased from 2279 to 6100. Furthermore, WPHs exhibited a strong capacity for icariin loading and micelle formation with critical micelle concentration values of 0.71, 0.99 and 1.09 mg mL-1, respectively. Moreover, similar immuno-enhancement activities were observed in WPHs. After exposure to WPHs, the pinocytosis of RAW264.7 macrophages was significantly improved. WPH treatment also increased the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in macrophages. Up-regulation of mRNA expressions of IL-6, inducible nitric oxide synthase (iNOS) and TNF-α was observed in a dose-dependent manner. CONCLUSION: The enhancement of functionality and bioactivity in WP can be achieved through the application of limited enzyme digestion with trypsin. This process effectively augments the nutritional value and utility of the protein, making it a valuable component in various dietary applications. © 2024 Society of Chemical Industry.

9.
Sci Total Environ ; 946: 174188, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38925393

ABSTRACT

Rice-crayfish farming systems (RCs) can help mitigate climate change by enhancing soil organic carbon (SOC) sequestration. However, the mechanisms that govern the responses of microbial residues carbon (MRC), a key component of SOC, in RCs are not fully understood. We conducted a 6-year field experiment comparing RCs and rice monoculture systems (RMs). Specifically, we explored how MRC formation and stabilization differ between the two systems and how those differences are linked to changes in the metabolic processes of microbes. Results showed that MRC levels in RCs were 5.2 % and 40.0 % higher in the topsoil and subsoil, respectively, compared to RMs, indicating depth-dependent effects. Notably, MRC accumulation and stabilization in RCs were promoted through a cascade of processes of dissolved organic carbon (DOC) accessibility-microbial metabolism-mineral protection. In addition, the mechanism of MRC accumulation in subsoil differed between the two systems. Specifically, RMs improved accessibility of DOC by reducing humification and aromaticity of subsoil DOC, which helped microbes access to resources at lower cost. This decreased the respiration rate of microbes, thereby increasing microbial carbon pump (MCP) efficiency and thus promoting MRC accumulation. By contrast, the crayfish in RCs facilitated carbon exchange between topsoil and subsoil through their burrowing behaviors. This increased carbon allocation for microbial metabolism in the subsoil, supporting a larger microbial population and thus enhancing the MCP capacity, while reducing MRC re-decomposition via enhanced mineral protection, further increasing subsoil MRC accumulation. That is, MRC accumulation in the subsoil of RCs was predominantly driven by microbial population numbers (MCP capacity) whereas that of RMs was mostly driven by microbial anabolic efficacy (MCP efficiency). Our findings reveal a key mechanism by which RCs promoted soil MRC accumulation and stabilization, highlighting the potential role of DOC accessibility-microbial metabolism-mineral protection pathway in regulating MRC accumulation and stabilization.


Subject(s)
Carbon , Oryza , Soil Microbiology , Soil , Oryza/metabolism , Carbon/metabolism , Animals , Soil/chemistry , Astacoidea/metabolism , Aquaculture/methods , Agriculture/methods , Carbon Sequestration
10.
Am J Transl Res ; 16(4): 1199-1208, 2024.
Article in English | MEDLINE | ID: mdl-38715823

ABSTRACT

OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) and total bile acid (TBA) levels in gestational hypertension and their combined predictive value for pregnancy outcome. METHODS: A total of 194 patients with gestational hypertension (GH), treated from June 2020 to May 2022, were included in this study. The patients were divided into two subgroups based on pregnancy outcome: an adverse pregnancy outcome group (77 cases) and a normal pregnancy outcome group (117 cases). Additionally, 50 healthy pregnant women undergoing routine prenatal checkups during the same period served as the control group. In this study, serum TBA and TSH levels were measured and compared between the control and GH groups as well as between adverse pregnancy outcome and normal pregnancy outcome groups. The independent risk factors for adverse pregnancy outcome were screened using logistic regression, and their predictive value for pregnancy outcome in patients with GH was analyzed using receiver operating characteristic (ROC) curves. RESULTS: Serum TSH and TBA levels were significantly higher in the GH group compared to the normal group (both P < 0.001). Logistic regression analysis revealed that age, body mass index (BMI), TSH, and TBA were independent risk factors for adverse pregnancy outcome. ROC curve analysis showed that combined TSH and TBA for predicting adverse pregnancy outcome had an Area Under the Curve (AUC) of 0.896, surpassing the AUCs of each individual index (0.843 for TSH and 0.765 for TBA), which indicates a stronger predictive value (P < 0.001). CONCLUSION: The combined measurement of serum TBA and TSH can serve as a valuable predictive tool for pregnancy outcome in patients with gestational hypertension.

11.
J Leukoc Biol ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776408

ABSTRACT

BACKGROUND: Aim to investigate the predictive value of changes in presepsin (PSEP), procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) levels to for mortality in septic patients in intensive care unit (ICU). METHOD: This study enrolled septic patients between November 2020 and December 2021. Levels of PSEP, PCT, hsCRP, and IL-6 were measured on 1st (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and 3rd day (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. RESULTS: The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional-hazards regression (Cox) analysis, △PSEP (= PSEP_3- PSEP_0) > 211.49 pg/ml (hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.17-6.22), △PCT (= PCT_3- PCT_0) > -0.13 ng/ml (HR 7.31, 95% CI 2.68-19.80), △hsCRP (= hsCRP_3- hsCRP_0) > -19.29 mg/L (HR 6.89, 95% CI 1.61-29.40), and △IL-6 (= IL-6_3- IL-6_0) > 1.00 pg/ml (HR 3.13, 95% CI 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all four distinct biomarkers was highest (concordance index 0.83, 95% CI 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the APACHE Ⅱ and SOFA scores, the combination of the four biomarkers had a larger net benefit. Interestingly, IL-6 was predominantly produced by monocytes upon LPS stimulation in PBMCs. CONCLUSIONS: △PSEP, △PCT, △hsCRP, and △IL-6 are reliable biomarkers for predicting mortality in septic patients in ICU, and their combination has the best performance.

12.
Emerg Microbes Infect ; 13(1): 2353298, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38721691

ABSTRACT

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.


Subject(s)
COVID-19 , Mycoplasma pneumoniae , Pneumonia, Mycoplasma , Humans , Pneumonia, Mycoplasma/epidemiology , Pneumonia, Mycoplasma/microbiology , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Mycoplasma pneumoniae/drug effects , China/epidemiology , COVID-19/epidemiology , COVID-19/transmission , Child , Retrospective Studies , Child, Preschool , Male , Female , Infant , Macrolides/pharmacology , Drug Resistance, Bacterial , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adolescent , High-Throughput Nucleotide Sequencing , Anti-Bacterial Agents/pharmacology , Pandemics
13.
Psychiatry Res ; 335: 115890, 2024 May.
Article in English | MEDLINE | ID: mdl-38579458

ABSTRACT

This systematic review and meta-analysis aimed to evaluate the impact of intraoperative and/or postoperative esketamine application on the prevention of postpartum depression (PPD). PubMed, Embase, and Web of Science were thoroughly searched for eligible randomized controlled trials (RCTs) regarding the application of esketamine for postnatal depression prevention. Nine RCTs including 1277 participants were involved in the final analysis. It was found that intraoperative and/or postoperative administration of esketamine significantly reduced the PPD incidence and the Edinburgh Postnatal Depression Scores in the early postoperative period. Meanwhile, esketamine lowered the occurrence of postoperative nausea and vomiting with no influence on other psychiatric symptoms.


Subject(s)
Depression, Postpartum , Ketamine , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Depression, Postpartum/prevention & control , Female
14.
Clin Neurol Neurosurg ; 239: 108229, 2024 04.
Article in English | MEDLINE | ID: mdl-38479036

ABSTRACT

OBJECTIVE: First, the efficacy and safety of aspirin-ticagrelor after cerebral artery stenting in ischemic stroke patients is controversial. Second, there is a gap in the research on guiding two antiplatelet therapy (DAPT) after stenting based on the CYP2C19 genotype. METHODS: This retrospective study included patients who underwent cerebral artery stenting at the First Affiliated Hospital of Chongqing Medical University from January 2019 to February 2023. We divided them into the aspirin-clopidogrel group and aspirin-ticagrelor group and carefully collected baseline information laboratory data and imaging results from the patients. The efficacy outcomes were 30 days recurrent stroke, 90 days recurrent stroke, and 180 days recurrent stroke, and the safety outcome was intracranial hemorrhage. T-tests or Fisher's tests were performed for study outcomes in both groups of patients. OUTCOME: A total of 372 patients were included. For efficacy outcomes, aspirin-ticagrelor was associated with a reduced risk of 180 days recurrent stroke, in patients with CYP2C19 LOF allele (OR = 0.426, CI = 0.184-0.986, P = 0.042) and CYP2C19 intermediate metabolic genotype (OR = 0.237, CI = 0.026-1.034, P = 0.044), compared with aspirin-clopidogrel. There was no significant difference in the rate of intracranial hemorrhage (ICH) between patients with aspirin-clopidogrel and aspirin-ticagrelor, regardless of overall (OR = 1.221, CI = 0.115-7.245, P = 0.683), CYP2C19 LOF allele carriers (OR = 1.226, CI = 0.411-3.658, P = 0.715), or CYP2C19 intermediate metabolizer (OR = 1.221, CI = 0.115-7.245, P = 0.683). No significant differences were found between the two DAPTs on other efficacy and safety outcomes. CONCLUSION: A cohort study found that aspirin-ticagrelor was significantly superior to aspirin-clopidogrel in reducing 180 days recurrent stroke in CYP2C19 LOF allele carriers and CYP2C19 intermediate metabolizers. There was no significant difference between aspirin-ticagrelor and aspirin-clopidogrel in the risk of intracranial hemorrhage in terms of ICH rates.


Subject(s)
Ischemic Stroke , Stroke , Humans , Clopidogrel/therapeutic use , Ticagrelor/adverse effects , Aspirin/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Cohort Studies , Retrospective Studies , Intracranial Hemorrhages/chemically induced , Cerebral Arteries , Stroke/genetics , Treatment Outcome
15.
Neuroscience ; 545: 125-140, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38484837

ABSTRACT

Chronic cerebral hypoperfusion (CCH) can cause vascular cognitive impairment and dementia. AT1R, angiotensin II type I receptor, plays a vital role in central nervous system pathologies, but its concrete function in vascular dementia is still unclear. Herein, we investigated the effects of AT1R during CCH by conditional knockout of the microglial AT1R and candesartan treatment. Using the bilateral carotid artery stenosis (BCAS) model, we found that the AT1R is crucial in exacerbating CCH-induced cognitive impairment via regulating microglial activation. The levels of AT1R were increased in the hippocampus and the hippocampal microglia after CCH induction. Microglial AT1R conditional knockout ameliorated cognitive impairment by reducing inflammatory responses and microglial activation, and so did candesartan treatment. However, we observed restoration of cerebral blood flow (CBF) but no significant neuronal loss in the hippocampus at 28 days after BCAS. Finally, we screened three hub genes (Ctss, Fcer1g, Tyrobp) associated with CCH. Our findings indicated that microglial expression of AT1R is critical for regulating neuroinflammation in CCH, and AT1R antagonism may be a feasible and promising method for ameliorating CCH-caused cognitive impairment.


Subject(s)
Cognitive Dysfunction , Mice, Knockout , Microglia , Receptor, Angiotensin, Type 1 , Animals , Male , Mice , Benzimidazoles/pharmacology , Biphenyl Compounds/pharmacology , Carotid Stenosis/complications , Cerebrovascular Circulation/physiology , Cerebrovascular Circulation/drug effects , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/drug therapy , Disease Models, Animal , Hippocampus/metabolism , Hippocampus/pathology , Hippocampus/drug effects , Mice, Inbred C57BL , Microglia/metabolism , Microglia/drug effects , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 1/genetics , Tetrazoles/pharmacology , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism
16.
Sci Technol Adv Mater ; 25(1): 2315013, 2024.
Article in English | MEDLINE | ID: mdl-38476511

ABSTRACT

The ever-growing use of nature-derived materials creates exciting opportunities for novel development in various therapeutic biomedical applications. Living cells, serving as the foundation of nanoarchitectonics, exhibit remarkable capabilities that enable the development of bioinspired and biomimetic systems, which will be explored in this review. To understand the foundation of this development, we first revisited the anatomy of cells to explore the characteristics of the building blocks of life that is relevant. Interestingly, animal cells have amazing capabilities due to the inherent functionalities in each specialized cell type. Notably, the versatility of cell membranes allows red blood cells and neutrophils' membranes to cloak inorganic nanoparticles that would naturally be eliminated by the immune system. This underscores how cell membranes facilitate interactions with the surroundings through recognition, targeting, signalling, exchange, and cargo attachment. The functionality of cell membrane-coated nanoparticles can be tailored and improved by strategically engineering the membrane, selecting from a variety of cell membranes with known distinct inherent properties. On the other hand, plant cells exhibit remarkable capabilities for synthesizing various nanoparticles. They play a role in the synthesis of metal, carbon-based, and polymer nanoparticles, used for applications such as antimicrobials or antioxidants. One of the versatile components in plant cells is found in the photosynthetic system, particularly the thylakoid, and the pigment chlorophyll. While there are challenges in consistently synthesizing these remarkable nanoparticles derived from nature, this exploration begins to unveil the endless possibilities in nanoarchitectonics research.


We have highlighted the Cell-derived Nanomaterials for Biomedical Applications through the lenses of our team who have experiences with working on cell membrane, thylakoids, and studying the impact of nanoparticles on biological phenomenon such as nanomaterialsinduced endothelial leakiness (NanoEL). In this review, we have discussed the progress and the wide potential of nanoarchitectonics in plant systems, animal cells and microorganisms. Due to our unique backgrounds, our take on this topic may be the novelty of the review.

17.
Diabetes Obes Metab ; 26(6): 2329-2338, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38488254

ABSTRACT

AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Predictive Value of Tests , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Male , Female , Middle Aged , Blood Glucose/analysis , Blood Glucose/metabolism , Follow-Up Studies , China/epidemiology , Glucose Tolerance Test , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Glucose Intolerance/blood , Glucose Intolerance/diagnosis , Glucose Intolerance/complications , Adult , Diabetes Complications/blood , Diabetes Complications/epidemiology , Aged , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/prevention & control , Diabetic Angiopathies/mortality , ROC Curve
18.
ACS Chem Neurosci ; 15(5): 1055-1062, 2024 03 06.
Article in English | MEDLINE | ID: mdl-38379141

ABSTRACT

Histidine behaviors play critical roles in folding and misfolding processes due to the changes in net charge and the various N/N-H orientations on imidazole rings. However, the effect of histidine tautomerization (HIE (Nε-H, ε) and HID (Nδ-H, δ) states) behaviors on the edge chain of Aß mature fibrils remains inadequately understood, which is critical for finding a strategy to disturb fibril elongation and growth. In the current study, eight independent molecular dynamics simulations were conducted to investigate such impacts on the structural and aggregation properties. Our results from three different binding models revealed that the binding contributions of edge substitution effects are primarily located between chains 1 and 2. Histidine states significantly influence the secondary structure of each domain. Further analysis confirmed that the C1_H6//C1_E11 intrachain interaction is essential in maintaining the internal stability of chain 1, while the C1_H13//C2_H13 and C1_H14//C2_H13 interchain interactions are critical in maintaining the interchain stability of the fibril structure. Our subsequent analysis revealed that the current edge substitution leads to the loss of the C1_H13//C1_E11 intrachain and C1_H13//C2_H14 interchain interactions. The N-terminal regularity was significantly directly influenced by histidine states, particularly by the residue of C1_H13. Our study provides valuable insights into the effect of histidine behaviors on the edge chain of Aß mature fibril, advancing our understanding of the histidine behavior hypothesis in misfolding diseases.


Subject(s)
Amyloid beta-Peptides , Histidine , Amyloid beta-Peptides/metabolism , Histidine/chemistry , Molecular Dynamics Simulation , Peptide Fragments/metabolism , Protein Aggregates
19.
World Neurosurg ; 184: e468-e485, 2024 04.
Article in English | MEDLINE | ID: mdl-38310951

ABSTRACT

BACKGROUND: This study aimed to establish a precise preoperative high-risk factor scoring system and algorithm for antibiotic prophylaxis decision-making, provide guidance for the judicious use of AMP, refine interventions, and ensure the appropriate application of AMP for class I incisions in neurosurgery. METHODS: According to PRISMA guidelines, literature searches, study selection, methodology development, and quality appraisal were performed. The quality of evidence across the study population was assessed using the Newcastle-Ottawa Scale. A two-round Delphi expert consultation method involved 15 experts from leading tertiary hospitals in China. Establishing an algorithm of SOPs for perioperative antimicrobial prophylaxis in Class I neurosurgical incisions. RESULTS: Thirteen studies, encompassing 11,936 patients undergoing clean neurosurgical procedures, were included. 791 patients experienced SSI, resulting in an average incidence of 6.62%. Identified risk factors significantly associated with an increased incidence of postoperative SSI (P < 0.05) included emergency surgery, preoperative hospitalization ≥7 days, intraoperative blood loss ≥300 mL, operation time ≥4 hours, diabetes mellitus, cerebrospinal fluid leakage, and repeat surgery. Sensitivity analysis demonstrated robust results for emergency surgery, intraoperative blood loss ≥300 mL, operation time ≥4 hours, cerebrospinal fluid leakage, and repeat surgery. Established a risk assessment system for Class I neurosurgical incisions by the Delphi method. Additionally, we have formulated an algorithm of SOPs for perioperative antimicrobial prophylaxis in Class I neurosurgical incisions. CONCLUSIONS: The established index for AMP utilization and SOPs in the preoperative period of class I neurosurgical incisions proves valuable, contributing to improved patient outcomes in neurosurgical procedures.


Subject(s)
Anti-Infective Agents , Neurosurgery , Surgical Wound , Humans , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Surgical Wound Infection/etiology , Blood Loss, Surgical , Neurosurgical Procedures/adverse effects , Antibiotic Prophylaxis/methods , Anti-Infective Agents/therapeutic use , Perioperative Period , Cerebrospinal Fluid Leak/etiology
20.
Maturitas ; 182: 107922, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38325136

ABSTRACT

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.


Subject(s)
Fertility Preservation , Menopause, Premature , Primary Ovarian Insufficiency , Female , Humans , Quality of Life , Cryopreservation , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/prevention & control , Iatrogenic Disease/prevention & control
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