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1.
Biochem Pharmacol ; : 116541, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39284501

ABSTRACT

Tetramethylpyrazine (TMP) belongs to the active ingredients of the traditional Chinese medicine Chuanxiong, which has a certain protective effect in myocardial ischemia-reperfusion (I/R) injury. It can improve postoperative cardiac function and alleviate ventricular remodeling in acute myocardial infarction patients. However, its specific protective mechanism is still unclear. In this study, a certain concentration of TMP was introduced into I/R mice or H9C2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to observe the effects of TMP on cardiomyocyte activity, cytotoxicity, apoptosis, autophagy, pyroptosis, and NLRP3 inflammasome activation. The results displayed that TMP intervention could reduce OGD/R and I/R-induced cardiomyocyte apoptosis, accelerate cellular activity and autophagy levels, and ameliorate myocardial tissue necrosis in I/R mice in a dose-dependent manner. Further, TMP prevented the formation of NLRP3 inflammasomes to suppress pyroptosis by increasing the level of cardiomyocyte autophagy after I/R and OGD/R modelling, the introduction of chloroquine to suppress autophagic activity in vivo and in vitro was further analyzed to confirm whether TMP inhibits NLRP3 inflammasome activation and pyroptosis by increasing autophagy, and we found the inhibitory effect of TMP on NLRP3 inflammasomes and its protective effect against myocardial injury were blocked when autophagy was inhibited with chloroquine. In conclusion, this experiment demonstrated that TMP unusually attenuated I/R injury in mice, and this protective effect was achieved by inhibiting the activation of NLRP3 inflammasomes through enhancing autophagic activity.

2.
Anal Methods ; 16(34): 5777-5784, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39145405

ABSTRACT

Sensitive, convenient and rapid detection and subtyping of influenza viruses are crucial for timely treatment and management of infected people. Compared with antigen detection, nucleic acid detection has higher specificity and can shorten the detection window. Hence, in this work, we improved the lateral flow assay (LFA, one of the most promising user-friendly and on-site methods) to achieve detection and subtyping of H1N1, H3N2 and H9N2 influenza virus nucleic acids. Firstly, the antigen-antibody recognition mode was transformed into a nucleic acid hybridization reaction. Secondly, Fe3O4-Au heterodimer nanoparticles were prepared to replace frequently used Au nanoparticles to obtain better coloration. Thirdly, four lines were arranged on the LFA strip, which were three test (T) lines and one control (C) line. Three T lines were respectively sprayed by the DNA sequences complementary to one end of H1N1, H3N2 and H9N2 influenza virus nucleic acids, while Fe3O4-Au nanoparticles were respectively coupled with the DNA sequences complementary to the other end of H1N1, H3N2 and H9N2 nucleic acids to construct three kinds of probes. The C line was sprayed by the complementary sequences to the DNAs on all three kinds of probes. In the detection, by hybridization reaction, the probes were combined with their target nucleic acids which were captured by the corresponding T lines to form color bands. Finally, according to the position of the color bands and their grey intensity, simultaneous qualitative and semi-quantitative detection of the three influenza virus nucleic acids was realized. The detection results showed that this multi-channel LFA had good specificity, and there was no significant cross reactivity among the three subtypes of influenza viruses. The simultaneous detection achieved comparable detection limits with individual detections. Therefore, this multi-channel LFA had good application potential for sensitive and rapid detection and subtyping of influenza viruses.


Subject(s)
Gold , Gold/chemistry , Humans , Influenza A Virus, H3N2 Subtype/chemistry , Influenza A Virus, H3N2 Subtype/isolation & purification , Metal Nanoparticles/chemistry , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H1N1 Subtype/chemistry , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H9N2 Subtype/chemistry , Influenza A Virus, H9N2 Subtype/isolation & purification , Nucleic Acid Hybridization/methods , DNA, Viral/analysis , Influenza, Human/diagnosis , Magnetite Nanoparticles/chemistry , Limit of Detection
3.
J Cell Physiol ; : e31364, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39129208

ABSTRACT

High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.

4.
Sci Rep ; 14(1): 17728, 2024 07 31.
Article in English | MEDLINE | ID: mdl-39085442

ABSTRACT

Heart failure (HF) is a significant global public health concern with a high readmission rate, posing a serious threat to the health of the elderly population. While several studies have used machine learning (ML) to develop all-cause readmission risk prediction models for elderly patients with HF, few have integrated ML-selected features with those chosen by human experts to assess HF patients readmission. A retrospective analysis of 8396 elderly HF patients hospitalized at the Affiliated Hospital of North Sichuan Medical College from January 1, 2018 to December 31, 2021 was conducted. Variables selected by XGBoost, LASSO regression, and random forest constituted the machine group, while the human expert group comprised variables chosen by two experienced cardiovascular professors. The variables selected by both groups were combined to form a human-machine collaboration group. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) method was used to elucidate the importance of each predictive feature, explain the impact of individual features on the model, and provide visual representation. A total of 73 features were included for model development. The human-machine collaboration model, utilizing CatBoost, achieved an AUC of 0.83617, an F1-score of 0.73521, and a Brier score of 0.16536 on the validation set. This model demonstrated superior predictive performance compared to those created solely by human experts or machine. The SHAP plot was then used to visually display the feature analysis of the human-machine collaboration model, revealing HGB, NT-proBNP, smoking history, NYHA classification, and LVEF as the 5 most important features. This study indicate that the human-machine collaboration model outperforms those relying solely on human expert selection or machine algorithm at predicting all-cause readmission in elderly HF patients. The application of the SHAP method enhanced the interpretability of the model outcomes, aiding clinicians in accurately pinpointing risk factors associated with HF readmission. This advancement enables the formulation of tailored treatment strategies, offering a more personalized approach to patient care.


Subject(s)
Heart Failure , Machine Learning , Patient Readmission , Humans , Heart Failure/epidemiology , Patient Readmission/statistics & numerical data , Aged , Female , Male , Retrospective Studies , Aged, 80 and over , Risk Factors , Risk Assessment/methods , ROC Curve
5.
Adv Mater ; : e2408159, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082060

ABSTRACT

Intelligent polymer nanocomposites are multicomponent and multifunctional materials that show immense potential across diverse applications. However, to exhibit intelligent traits such as adaptability, reconfigurability and dynamic properties, these materials often require a solvent or heating environment to facilitate the mobility of polymer chains and nanoparticles, rendering their applications in everyday settings impractical. Here intelligent azopolymer nanocomposites that function effectively in a solvent-free, room-temperature environment based on photocontrolled reversible solid-fluid transitions via switching flow temperatures (Tfs) are shown. A range of nanocomposites is synthesized through the grafting of Au nanoparticles, Au nanorods, quantum dots, or superparamagnetic nanoparticles with photoresponsive azopolymers. Leveraging the reversible cis-trans photoisomerization of azo groups, the azopolymer nanocomposites transition between solid (Tf above room temperature) and fluid (Tf below room temperature) states. Such photocontrolled reversible solid-fluid transitions empower the rewriting of nanopatterns, correction of nanoscale defects, reconfiguration of complex multiscale structures, and design of intelligent optical devices. These findings highlight Tf-switchable polymer nanocomposites as promising candidates for the development of intelligent nanomaterials operative in solvent-free, room-temperature conditions.

6.
Clin Chim Acta ; 561: 119812, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38876250

ABSTRACT

GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a form of renal Fanconi syndrome (RFS), which is a disorder of solute and water reabsorption caused by defects in the function of the entire proximal tubule. Recent findings reveal the molecular basis of FRTS1: Intramitochondrial fiber aggregation triggered by mutant GATM provides a starting point for proximal tubule damage and drives disease progression. As a rare and newly recognized inherited kidney disease, the complex manifestations of FRTS1 are easily underdiagnosed or misdiagnosed. We discuss the complex phenotype of a 26-year-old woman with onset in infancy and a long history of hypophosphatemic rickets. We also identified a novel heterozygous missense variant in the GATM gene in this patient. The novel variant and phenotype we report expand the disease spectrum of FRTS1. We recommend screening for GATM in children with RFS, especially in patients with resistant rickets who have previously had negative genetic testing. In addition, we found pathological deposition of mutant GATM proteins within mitochondria in the patient's urinary sediment cells by a combination of electron microscopy and immunofluorescence. This unique urine cytology experiment has the potential to be a valuable tool for identifying patients with RRTS1.


Subject(s)
Fanconi Syndrome , Phenotype , Rickets, Hypophosphatemic , Humans , Female , Adult , Fanconi Syndrome/genetics , Fanconi Syndrome/diagnosis , Fanconi Syndrome/pathology , Rickets, Hypophosphatemic/genetics , Rickets, Hypophosphatemic/diagnosis , Mutation, Missense
7.
Sci Rep ; 14(1): 13393, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862634

ABSTRACT

To investigate the factors that influence readmissions in patients with acute non-ST elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI) by using multiple machine learning (ML) methods to establish a predictive model. In this study, 1576 NSTEMI patients who were hospitalized at the Affiliated Hospital of North Sichuan Medical College were selected as the research subjects. They were divided into two groups: the readmitted group and the non-readmitted group. The division was based on whether the patients experienced complications or another incident of myocardial infarction within one year after undergoing PCI. Common variables selected by univariate and multivariate logistic regression, LASSO regression, and random forest were used as independent influencing factors for NSTEMI patients' readmissions after PCI. Six different ML models were constructed using these common variables. The area under the ROC curve, accuracy, sensitivity, and specificity were used to evaluate the performance of the six ML models. Finally, the optimal model was selected, and a nomogram was created to visually represent its clinical effectiveness. Three different methods were used to select seven representative common variables. These variables were then utilized to construct six different ML models, which were subsequently compared. The findings indicated that the LR model exhibited the most optimal performance in terms of AUC, accuracy, sensitivity, and specificity. The outcome, admission mode (walking and non-walking), communication ability, CRP, TC, HDL, and LDL were identified as independent predicators of readmissions in NSTEMI patients after PCI. The prediction model constructed by the LR algorithm was the best. The established column graph model established proved to be effective in identifying high-risk groups with high accuracy and differentiation. It holds a specific predictive value for the occurrence of readmissions after direct PCI in NSTEMI patients.


Subject(s)
Machine Learning , Non-ST Elevated Myocardial Infarction , Patient Readmission , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Patient Readmission/statistics & numerical data , Male , Female , Non-ST Elevated Myocardial Infarction/surgery , Middle Aged , Aged , Risk Factors , Risk Assessment/methods , ROC Curve
8.
Org Lett ; 26(18): 3987-3990, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38690833

ABSTRACT

Highly efficient kinetic resolution of P-chiral phosphindole oxides via rhodium-catalyzed asymmetric arylation under mild conditions is described. Selectivity factors of up to 569 were achieved by employing chiral diene* as a ligand. The transformation of the enantiopure benzophosphole derivative into a useful P-chiral bisphosphine ligand is also demonstrated.

9.
BMC Genomics ; 25(1): 453, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720243

ABSTRACT

BACKGROUND: Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking. RESULTS: In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds. CONCLUSIONS: We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.


Subject(s)
Cytochrome P-450 Enzyme System , Evolution, Molecular , Phylogeny , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Animals , Multigene Family , Genome, Insect , Insect Proteins/genetics , Insect Proteins/metabolism , Female , Gene Expression Profiling
10.
ACS Appl Mater Interfaces ; 16(15): 18459-18473, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38578815

ABSTRACT

Reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) hold great promise for tumor treatment. However, hypoxia, insufficient H2O2, and overexpressed glutathione (GSH) in the tumor microenvironment (TME) hinder ROS generation significantly. Herein, we reported CaO2@Cu-TCPP/CUR with O2/H2O2/Ca2+ self-supply and GSH depletion for enhanced PDT/CDT and Ca2+ overload synergistic therapy. CaO2 nanospheres were first prepared and used as templates for guiding the coordination between the carboxyl of tetra-(4-carboxyphenyl)porphine (TCPP) and Cu2+ ions as hollow CaO2@Cu-TCPP, which facilitated GSH-activated TCPP-based PDT and Cu+-mediated CDT. The hollow structure was then loaded with curcumin (CUR) to form CaO2@Cu-TCPP/CUR composites. Cu-TCPP prevented degradation of CaO2, while Cu2+ ions reacted with GSH to deplete GSH, produce Cu+ ions, and release TCPP, CaO2, and CUR. CaO2 reacted with H2O to generate O2, H2O2, and Ca2+ to achieve O2/H2O2/Ca2+ self-supply for TCPP-based PDT, Cu+-mediated CDT, and CUR-enhanced Ca2+ overload therapy. Thus, this multilevel ROS amplifier enhances synergistic therapy with fewer side effects and drug resistance.


Subject(s)
Curcumin , Nanospheres , Neoplasms , Photochemotherapy , Humans , Reactive Oxygen Species , Hydrogen Peroxide , Glutathione , Tumor Microenvironment , Cell Line, Tumor , Oxygen
11.
Biomed Environ Sci ; 37(2): 157-169, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38582978

ABSTRACT

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Rifampin/pharmacology , Retrospective Studies , Drug Resistance, Multiple, Bacterial/genetics , Microbial Sensitivity Tests , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Mutation
12.
Respir Care ; 69(9): 1108-1115, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-38688549

ABSTRACT

BACKGROUND: A protocolized extubation readiness test (ERT), including a spontaneous breathing trial (SBT), is recommended for patients who are intubated. This quality-improvement project aimed to improve peri-extubation outcomes by using a high-risk ERT protocol in intubated cardiac patients in addition to a standard-risk protocol. METHODS: After baseline data collection, we implemented a standard-risk ERT protocol (pressure support plus PEEP), followed by a high-risk ERT protocol (PEEP alone) in cardiac subjects who were intubated. The primary outcome, a composite of extubation failure and rescue noninvasive respiratory support, was compared between phases. Ventilator duration and use of postextubation respiratory support were balancing measures. RESULTS: A total of 213 cardiac subjects who were intubated were studied, with extubation failure and rescue noninvasive respiratory support occurring in 10 of 213 (4.7%) and 8 of 213 (3.8%), respectively. We observed a reduction in the composite outcome among the 3 consecutive phases (5/29 [17.2%], 10/110 [9.1%] vs 3/74 [4.1%]; P = .10), but this did not reach statistical significance. In the logistic regression model when adjusting for admission type, the high-risk ERT protocol was associated with a significant reduction of the composite outcome (adjusted odds ratio 0.20, 95% CI 0.04-0.091; P = .037), whereas the standard-risk ERT protocol was not (adjusted odds ratio 0.48, 95% CI 0.15-1.53; P = .21). This was not accompanied by a longer ventilator duration (2.0 [1.0, 3.0], 2.0 [1.0-4.0], vs adjusted odds ratio 2.0 [95% [1.0-6.0]; P = .99) or an increased use of planned noninvasive respiratory support (10/29 [35.5%], 35/110 [31.8%], vs 25/74 [33.8%]; P > .99). CONCLUSIONS: In this quality-improvement project, a high-risk ERT protocol was implemented with improvement in peri-extubation outcomes among cardiac subjects.


Subject(s)
Airway Extubation , Critical Illness , Quality Improvement , Ventilator Weaning , Humans , Male , Female , Infant , Ventilator Weaning/methods , Critical Illness/therapy , Child, Preschool , Child , Positive-Pressure Respiration/methods , Heart Diseases/therapy , Heart Diseases/physiopathology , Intubation, Intratracheal , Logistic Models , Noninvasive Ventilation/methods , Clinical Protocols
13.
Viruses ; 16(3)2024 02 27.
Article in English | MEDLINE | ID: mdl-38543730

ABSTRACT

Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae-induced cardiovascular injury and illuminate prospective therapeutic avenues.


Subject(s)
Cardiovascular Diseases , Flaviviridae Infections , Flaviviridae , Flavivirus , Humans , Cardiovascular Diseases/epidemiology , Flaviviridae/genetics , Hepacivirus
14.
Respir Care ; 69(4): 422-429, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538015

ABSTRACT

BACKGROUND: Postextubation respiratory support in pediatric ARDS may be used to support the recovering respiratory system and promote timely, successful liberation from mechanical ventilation. This study's aims were to (1) describe the use of postextubation respiratory support in pediatric ARDS from the time of extubation to hospital discharge, (2) identify potential risk factors for postextubation respiratory support, and (3) provide preliminary data for future larger studies. METHODS: This pilot single-center prospective cohort study recruited subjects with pediatric ARDS. Subjects' respiratory status up to hospital discharge, the use of postextubation respiratory support, and how it changed over time were recorded. Analysis was performed comparing subjects who received postextubation respiratory support versus those who did not and compared its use among pediatric ARDS severity categories. Multivariable logistic regression was used to determine variables associated with the use of postextubation respiratory support and included oxygenation index (OI), ventilator duration, and weight. RESULTS: Seventy-three subjects with pediatric ARDS, with median age and OI of 4 (0.6-10.5) y and 7.3 (4.9-12.7), respectively, were analyzed. Postextubation respiratory support was provided to 54/73 (74%) subjects: 28/45 (62.2%), 19/21 (90.5%), and 7/7 (100%) for mild, moderate, and severe pediatric ARDS, respectively, (P = .01). OI and mechanical ventilation duration were higher in subjects who received postextubation respiratory support (8.7 [5.4-14] vs 4.6 [3.7-7], P < .001 and 10 [7-17] d vs 4 [2-7] d, P < .001) compared to those who did not. At hospital discharge, 12/67 (18.2%) survivors received home respiratory support (6 subjects died prior to hospital discharge). In the multivariable model, ventilator duration (adjusted odds ratio 1.3 [95% CI 1.0-1.7], P = .050) and weight (adjusted odds ratio 0.95 [95% CI 0.91-0.99], P = .02) were associated with the use of postextubation respiratory support. CONCLUSIONS: The majority of intubated subjects with pediatric ARDS received respiratory support postextubation, and a substantial proportion continued to require it up to hospital discharge.


Subject(s)
Airway Extubation , Respiratory Distress Syndrome , Humans , Child , Airway Extubation/adverse effects , Prospective Studies , Respiration, Artificial/adverse effects , Risk Factors , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/etiology
15.
Org Lett ; 26(7): 1364-1369, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38358273

ABSTRACT

The reaction of 4/5-carbonyl-cycloalkenone 1 or its achiral isomer 1' with organoboronic acid 2 in the presence of a chiral diene (S,S)-Fc-tfb-rhodium catalyst gave disubstituted trans-cycloalkanone 3 with high diastereo- and enantioselectivity. This highly efficient dynamic kinetic resolution is achieved by fast racemization of 1 through the formation of a dienolate followed by kinetic resolution with the chiral catalyst. The utility is demonstrated by the synthesis of key intermediates en route to (-)-cannabidiol.

16.
Clin Exp Pharmacol Physiol ; 51(4): e13845, 2024 04.
Article in English | MEDLINE | ID: mdl-38382550

ABSTRACT

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.


Subject(s)
Apigenin , Atherosclerosis , Glucuronates , Inflammasomes , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Foam Cells/metabolism , Foam Cells/pathology , Muscle, Smooth, Vascular/metabolism , Oleic Acid/pharmacology , Oleic Acid/metabolism , Atherosclerosis/metabolism , Autophagy , RNA, Messenger/metabolism , Myocytes, Smooth Muscle/metabolism
17.
Anal Chem ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38317503

ABSTRACT

Lateral flow immunoassay (LFIA) has played a vital role in point-of-care (POC) testing on account of its simplicity, rapidity, and low cost. However, the low sensitivity and difficulty of quantitation limit its further development. Sensitive markers with new detection modes are being developed to dramatically improve LFIA's performance. Herein, a ligand-complex approach was proposed to uniformly coat a thin layer of Au onto Ag triangular nanoplates (Ag TNPs) without etching the Ag cores, which not only retain the unique optical properties from Ag TNPs but also acquire the surface stability and biocompatibility of gold. The localized surface plasmon resonance absorption of these Ag@Au TNPs could be finely adjusted from visible (550 nm) to the second near-infrared region (NIR-II) (1100 nm), and even longer, by simply adjusting the ratio between edge length and thickness. Utilizing the Ag@Au TNPs as new markers for LFIA, a highly sensitive colorimetric and photothermal dual-mode detection of the SARS-CoV-2 nucleocapsid protein was achieved with a very low background. The Ag@Au TNPs showed an exceedingly high photothermal conversion efficiency of 61.4% (ca. 2 times higher than that of Au nanorods), endowing the LFIA method with a low photothermal detection limit (40 pg/mL), which was 25-fold lower than that of the colorimetric results. The generality of the method was further verified by the sensitive and accurate analysis of cardiac troponin I (cTnI). This method is robust, reproducible, and highly specific and has been successfully applied to SARS-COV-2 detection in 35 clinical samples with satisfactory results, demonstrating its potential for POC applications.

18.
Pediatr Res ; 95(6): 1432-1440, 2024 May.
Article in English | MEDLINE | ID: mdl-38253876

ABSTRACT

BACKGROUND: Irritable bowel syndrome is common in children and exhibits a high placebo response. This study was to explore the placebo response rate and its influencing factors in children with irritable bowel syndrome. METHODS: A systematic search was performed on Pubmed, Embase, MEDLINE, Cochrane Library, CNKI, Wanfang, and CBM from database inception to March 2022. Randomized controlled trials of irritable bowel syndrome in children were included in the study. The primary outcome was the placebo response rate of improvement. RESULTS: Thirteen studies were included, with 445 patients in the placebo group. The rate of improvement and abdominal pain disappearance were 28.2% (95% CI, 16.6-39.9%) and 5% (95% CI, 0-18.4%). The placebo response based on the abdominal pain score was 0.675 (95% CI, 0.203-1.147). The mode of administration (P < 0.01), dosing schedule (P < 0.01), and clinical outcome assessor (P = 0.04) have a significant impact on the magnitude of placebo effect. CONCLUSIONS: The placebo response rate for pediatric irritable bowel syndrome was 28.2%. In clinical trials, reducing dosing frequency, selecting appropriate dosage forms, and using patient-reported outcomes can help mitigate the placebo effect. IMPACT: This is the first meta-analysis to assess the placebo response rates for improvement and disappearance in children with IBS. The finding suggested that the mode of administration, dosing schedule, and clinical outcome assessor could potentially influence the magnitude of the placebo effect in children with IBS. This study would provide a basis for estimating sample size in clinical trial design with a placebo control.


Subject(s)
Abdominal Pain , Irritable Bowel Syndrome , Placebo Effect , Adolescent , Child , Child, Preschool , Female , Humans , Abdominal Pain/drug therapy , Irritable Bowel Syndrome/drug therapy , Placebos , Randomized Controlled Trials as Topic , Treatment Outcome
19.
Adv Mater ; 36(11): e2307518, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38041802

ABSTRACT

On the path of persisting Moore's Law, one of the biggest obstacles is the "Boltzmann tyranny," which defines the lower limit of power consumption of individual transistors. Negative capacitance (NC) in ferroelectrics could provide a solution and has garnered significant attention in the fields of nanoelectronics, materials science, and solid-state physics. Molecular ferroelectrics, as an integral part of ferroelectrics, have developed rapidly in terms of both performance and functionality, with their inherent advantages such as easy fabrication, mechanical flexibility, low processing temperature, and structural tunability. However, studies on the NC in molecular ferroelectrics are limited. In this study, the focus is centered on the fabricated high-quality thin films of trimethylchloromethyl ammonium trichlorocadmium(II), and a pioneering investigation on their NC responses is conducted. The findings demonstrate that the NC exhibited by molecular ferroelectrics is comparable to that of conventional HfO2 -based ferroelectrics. This underscores the potential of molecular material systems for next-generation electronic devices.

20.
ACS Appl Mater Interfaces ; 15(42): 49583-49594, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37823823

ABSTRACT

The performance of contact resistive pressure sensors heavily relies on the intrinsic characteristics of the active layers, including the mechanical surface structure, conductivity, and elastic properties. However, efficiently and simply regulating the conductivity, morphology, and modulus of the active layers has remained a challenge. In this study, we introduced electro-polymerized polypyrrole (ePPy) to design flexible contact piezoresistive sensors with tailored intrinsic properties. The customizable intrinsic property of ePPy was comprehensively illustrated on the chemical and electronic structure scale, and the impact of ePPy's intrinsic properties on the sensing performance of the device was investigated by determining the correlation between resistivity, roughness, and device sensitivity. Due to the synergistic effects of roughness, conductivity, and elastic properties of the active layers, the flexible ePPy-based pressure sensor exhibited high sensitivity (3.19 kPa-1, 1-10 kPa, R2 = 0.97), fast response time, good durability, and low power consumption. These advantages allowed the sensor to offer an immediate response to human motion such as finger-bending and grasping movements, demonstrating the promising potential of tailorable ePPy-based contact piezoresistive sensors for wearable electronic applications.

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