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1.
Adv Sci (Weinh) ; : e2404266, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986026

RESUMO

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge. Herein, an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late-stage modify pharmaceuticals, scalability to large-scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd-catalyzed double isocyanide insertion process, thereby selectively providing the desired α-ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, confirming that they are probable intermediates in the catalytic pathway.

2.
J Gastrointest Oncol ; 15(3): 1060-1071, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38989415

RESUMO

Background: Patients with rectal cancer undergoing laparoscopic anterior resection and diverting stomas often suffer from bowel dysfunction after stoma closure, impairing their quality of life. This study aims to develop a machine learning tool to predict bowel function after diverting stoma closure. Methods: Clinicopathological data and post-operative follow-up information from patients with mid-low rectal cancer after diverting stoma closure were collected and analyzed. Patients were randomly divided into training and test sets in a 7:3 ratio. A machine learning model was developed in the training set to predict major low anterior resection syndrome (LARS) and evaluated in the test set. Decision curve analysis (DCA) was used to assess clinical utility. Results: The study included 396 eligible patients who underwent laparoscopic anterior resection and diverting stoma in Tongji Hospital affiliated with Huazhong University of Science and Technology from 1 January 2012 to 31 December 2020. The interval between stoma creation and closure, neoadjuvant therapy, and body mass index were identified as the three most crucial characteristics associated with patients experiencing major LARS in our cohort. The machine learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.78 [95% confidence interval (CI): 0.74-0.83] in the training set (n=277) and 0.74 (95% CI: 0.70-0.79) in the test set (n=119), and area under the precision-recall curve (AUPRC) of 0.73 and 0.69, respectively, with sensitivity of 0.67 and specificity of 0.66 for the test set. DCA confirmed clinical applicability. Conclusions: This study developed a machine learning model to predict major LARS in rectal cancer patients after diverting stoma closure, aiding their decision-making and counseling.

3.
Acta Pharm Sin B ; 14(7): 3068-3085, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027244

RESUMO

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

4.
Nat Commun ; 15(1): 5054, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871698

RESUMO

Photoluminescence (PL) colour-changing materials in response to photostimulus play an increasingly significant role in intelligent applications for their programmability. Nevertheless, current research mainly focuses on photochemical processes, with less attention to PL transformation through uniform aggregation mode adjustment. Here we show photochromic luminescence in organic crystals (e.g. dimethyl terephthalate) with PL varying from dark blue to purple, then to bright orange-red, and finally to red. This change is attributed to the emergence of clusters with red emission, which is barely achieved in single-benzene-based structures, thanks to the subtle molecular rearrangements prompted by light. Crucial to this process are the through-space electron interactions among molecules and moderate short contacts between ester groups. The irradiated crystals exhibit reversible PL transformation upon sufficient relaxation, showing promising applications in information storage and smart optoelectronic devices. This research contributes to the development of smart photochromic luminescent materials with significant PL colour transformations through molecular rearrangement.

5.
J Clin Nurs ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867609

RESUMO

AIMS: To investigate the prevalence of physical inactivity in older adults living in nursing homes and explore the determinants of physical inactivity by using the Capability, Opportunity, Motivation-Behaviour model. DESIGN: A multisite, cross-sectional study was performed by convenience sampling and questionnaire survey. METHODS: A total of 390 nursing home residents were recruited from three nursing homes in Southern China from May 2022 to April 2023. The participants completed a self-designed general information questionnaire, Physical Activity Scale for the Elderly, Self-Efficacy for Exercise Scale, Exercise Benefits Scale, Patient Health Questionnaire-9 and the Short Physical Performance Battery test. Descriptive statistics, univariate analysis, Spearman correlation analysis, and ordinal logistic regression were applied for data analysis. RESULTS: The prevalence of physical inactivity among the nursing home residents reached 88.46%. Ordinal logistic regression results showed that exercise self-efficacy, perceived exercise benefits, physical function, availability of physical activity instruction, having depression, number of chronic diseases and living with spouse were the main influencing determinants of physical inactivity and explained 63.7% of the variance. CONCLUSIONS: Physical inactivity was considerable in nursing home residents in China and influenced by complex factors. Tailored measures should be designed and implemented based on these factors to enhance physical activity while considering the uniqueness of Chinese culture. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Healthcare professionals should enhance physical activity of residents by increasing benefits understanding, boosting self-efficacy, improving physical function, alleviating depression and integrating personalized physical activity guidance into routine care services. And more attention should be paid to the residents who had more chronic diseases or did not live with spouse. IMPACT: Physical inactivity is a significant problem in nursing home residents. Understanding physical inactivity and its determinants enables the development of tailored interventions to enhance their physical activity level. REPORTING METHOD: This study was reported conforming to the STROBE statement. PATIENTS OR PUBLIC CONTRIBUTION: Nursing home residents who met the inclusion criteria were recruited.

6.
J Ethnopharmacol ; 333: 118409, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38823662

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.


Assuntos
Mineração de Dados , Plantas Medicinais , Índia , China , Plantas Medicinais/química , Humanos , Mineração de Dados/métodos , Medicina Tradicional Chinesa/métodos , Medicina Tradicional/métodos , Fitoterapia/métodos
7.
Huan Jing Ke Xue ; 45(6): 3605-3613, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897780

RESUMO

It is of great significance for the conservation of biodiversity in farmland ecosystems to study the diversity, structure, functions, and biogeographical distribution of soil microbes in farmland and their influencing factors. High-throughput sequencing technology was used to analyze the distribution characteristics of soil bacterial diversity, community structure, and metabolic function along elevation and their responses to soil physicochemical properties in farmland in the loess hilly areas of Ningxia. The results showed that:① The Alpha diversity index of soil bacterial was significantly negatively correlated with elevation (P < 0.05) and showed a trend of decreasing and then slightly increasing along the elevation. ② Seven phyla, including Proteobacteria, Actinobacteria, and Acidobacteria, were the dominant groups, and five of them showed highly significant differences between altitudes (P < 0.01). ③ At the secondary classification level, there were 36 metabolic functions of bacteria, including membrane transport, carbohydrate metabolism, and amino acid metabolism, of which 22 showed significant differences, and 12 showed extremely significant differences among different altitudes. ④ Pearson correlation analysis showed that soil water content, bulk density, pH, and carbon-nitrogen ratio had the most significant effects on bacterial Alpha diversity, whereas soil nutrients such as total organic carbon, total nitrogen, and total phosphorus had significant effects on bacterial Beta diversity. ⑤ Mantel test analysis showed that the soil water content, total organic carbon, and carbon-nitrogen ratio affected bacterial community structure at the phylum level, and soil pH, total organic carbon, total nitrogen, total phosphorus, and carbon-nitrogen ratio were significantly correlated with bacterial metabolic function. Variance partitioning analysis showed that soil water content had the highest explanation for the community structure of soil bacteria, whereas soil pH had the highest explanation for metabolic function. In conclusion, soil water content and pH were the main factors affecting the diversity, community composition, and metabolic function of soil bacteria in farmland in the loess hilly region of Ningxia.


Assuntos
Altitude , Bactérias , Microbiologia do Solo , China , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Solo/química , Biodiversidade , Produtos Agrícolas/crescimento & desenvolvimento , Proteobactérias/isolamento & purificação , Proteobactérias/crescimento & desenvolvimento , Nitrogênio/análise , Actinobacteria/crescimento & desenvolvimento , Ecossistema , Acidobacteria/crescimento & desenvolvimento , Acidobacteria/genética , Acidobacteria/isolamento & purificação , Fósforo/análise
8.
Angew Chem Int Ed Engl ; : e202406651, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781352

RESUMO

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo-phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood-rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room-temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments.

9.
Respir Res ; 25(1): 223, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811936

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.


Assuntos
Infecções Comunitárias Adquiridas , Microbiota , Índice de Gravidade de Doença , Escarro , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Masculino , Feminino , Escarro/microbiologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos Longitudinais , Estudos de Coortes , Disbiose/microbiologia , Disbiose/diagnóstico , Pneumonia/microbiologia , Pneumonia/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Idoso de 80 Anos ou mais , Adulto
10.
Respir Res ; 25(1): 173, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643126

RESUMO

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.


Assuntos
Disbiose , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pulmão , Haemophilus , Escarro/microbiologia , Progressão da Doença
11.
Phytomedicine ; 128: 155543, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657364

RESUMO

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.


Assuntos
Fator Apoptótico 1 Ativador de Proteases , Isquemia Encefálica , Medicamentos de Ervas Chinesas , Metabolômica , Ratos Sprague-Dawley , Animais , Isquemia Encefálica/tratamento farmacológico , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Apoptose/efeitos dos fármacos , Cromatografia Líquida , Simulação de Acoplamento Molecular , Medicina Tradicional Tibetana , Espectrometria de Massas , Espectrometria de Massa com Cromatografia Líquida
12.
Respir Res ; 25(1): 165, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622589

RESUMO

Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10-5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10-8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.


Assuntos
Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Microbiota/genética , Escarro , Transcriptoma , Genética Humana , Proteínas Adaptadoras de Transdução de Sinal/genética
13.
Front Pharmacol ; 15: 1338725, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495096

RESUMO

Introduction: The toxicity of arsenic is widely recognized globally, mainly harming human health by polluting water, soil, and food. However, its formulations can also be used for the clinical treatment of diseases such as leukemia and tumors. Arsenic has been used as a drug in China for over 2,400 years, with examples such as the arsenic-containing drug realgar mentioned in Shennong's Herbal Classic. We have reviewed references on arsenic over the past thirty years and found that research has mainly focused on clinical, pharmacological, and toxicological aspects. Results and Discussion: The finding showed that in clinical practice, arsenic trioxide is mainly used in combination with all-trans retinoic acid (ATRA) at a dose of 10 mg/d for the treatment of acute promyelocytic leukemia (APL); realgar can be used to treat acute promyelocytic leukemia, myelodysplastic syndrome, and lymphoma. In terms of pharmacology, arsenic mainly exerts anti-tumor effects. The dosage range of the action is 0.01-80 µmol/L, and the concentration of arsenic in most studies does not exceed 20 µmol/L. The pharmacological effects of realgar include antiviral activity, inhibition of overactivated lactate dehydrogenase, and resistance to malaria parasites. In terms of toxicity, arsenic is toxic to multiple systems in a dose-dependent manner. For example, 5 µmol/L sodium arsenite can induce liver oxidative damage and promote the expression of pro-inflammatory factors, and 15 µmol/L sodium arsenite induces myocardial injury; when the concentration is higher, it is more likely to cause toxic damage.

14.
Clin Interv Aging ; 19: 529-538, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525315

RESUMO

Purpose: To evaluate the performance of the Framingham cardiovascular risk score (FRS)/pooled cohort equations (PCE)/China prediction for atherosclerotic cardiovascular disease (ASCVD) risk (China-PAR model) in a prospective cohort of Chinese older adults. Patients and Methods: We assessed 717 older adults aged 75-85 years without ASCVD at the baseline from the Sichuan province of China. The participants were followed annually from 2011 to 2021. We obtained the participants' information through the medical records of physical examination and evaluated their 10-year ASCVD risk using FRS, PCE, and China-PAR. We further evaluated the predictive abilities of three assessment models. Results: During the 10-year follow-up, 206 participants developed ASCVD, with an incidence rate of 28.73%. The FRS and China-PAR moderately underestimated the risk of ASCVD (22.1% and 12.4%, respectively), but while PCE overestimated the risk (36.1%). FRS and China-PAR were found to underestimate the risk of ASCVD (26% and 63%, respectively) for men, while PCE overestimated the risk by 8%; For women, FRS and China-PAR were found to underestimate the risk of ASCVD (14% and 35%, respectively), while PCE overestimated the risk by 88%. Conclusion: The 10-year ASCVD risk was found to be overestimated by PCE. China-PAR had the most accurate predictions in women, while FRS was particularly well-calibrated in males. All three risk models have good discrimination, with FRS and PCE being well-calibrated in men and all three being well-calibrated in women. Therefore, accurate risk models are warranted to facilitate the prevention of ASCVD at the baseline among Chinese older adults.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Masculino , Humanos , Feminino , Idoso , Fatores de Risco , Medição de Risco , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Aterosclerose/epidemiologia
15.
Angew Chem Int Ed Engl ; 63(18): e202400538, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38419141

RESUMO

Interactions between host and bacterial cells are integral to human physiology. The complexity of host-microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high-resolution approaches to capture their full complexity. The latest breakthroughs in single-cell RNA sequencing (scRNA-seq) have opened up a new era of studies in host-pathogen interactions. Here, we first report a high-throughput cross-species dual scRNA-seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom-seq). Using reference cells, scRandom-seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom-seq witnessed polarization of THP-1 derived-macrophages and the intracellular A.b-induced ferroptosis-stress in host cells. The inhibition of ferroptosis by Ferrostatin-1 (Fer-1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom-seq provides a high-throughput cross-species dual single-cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host-microbe interactions in infection systems and tumor micro-environments.


Assuntos
Acinetobacter baumannii , Ferroptose , Humanos , Sequenciamento de Nucleotídeos em Larga Escala , Macrófagos/microbiologia , Análise de Sequência de RNA/métodos , Análise de Célula Única
17.
Small Methods ; 8(2): e2300243, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37491782

RESUMO

Polymer-based room-temperature phosphorescence (RTP) materials, especially polysaccharide-based RTP materials, earn sustained attention in the fields of anti-counterfeiting, data encryption, and optoelectronics owing to their green regeneration, flexibility, and transparency. However, those with both ultralong phosphorescence lifetime and excitation wavelength-dependent afterglow are rarely reported. Herein, a kind of amorphous RTP material with ultralong lifetime of up to 2.52 s is fabricated by covalently bonding sodium alginate (SA) with arylboronic acid in the aqueous phase. The resulting polymer film exhibits distinguished RTP performance with excitation-dependent emissions from cyan to green. Specifically, by co-doping with other fluorescent dyes, further regulation of the afterglow color from cyan to yellowish-green and near-white can be achieved through triplet-to-singlet Förster resonance energy transfer. In addition, the water-sensitive properties of hydrogen bonds endow the RTP property of SA-based materials with water/heat-responsive characteristics. On account of the color-tunable and stimuli-responsive afterglows, these smart materials are successfully applied in data encryption and anti-counterfeiting.

18.
Nicotine Tob Res ; 26(4): 474-483, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-37535700

RESUMO

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Camundongos , Animais , Masculino , Humanos , Nicotina/efeitos adversos , Nicotina/metabolismo , Camundongos Endogâmicos C57BL , Pulmão , Aerossóis/farmacologia
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013592

RESUMO

Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE

20.
J Ethnopharmacol ; 319(Pt 2): 117310, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37827296

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368-1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. AIM OF THE STUDY: In this study, a metabonomics study based on ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. MATERIALS AND METHODS: This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. RESULTS: Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP-kynurequinolinic acid and succinylornithine-urea cycle-NO metabolic pathways. CONCLUSIONS: This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored.


Assuntos
Isquemia Encefálica , Erigeron , AVC Isquêmico , Traumatismo por Reperfusão , Ratos , Animais , Erigeron/química , Simulação de Acoplamento Molecular , Leucina/uso terapêutico , China , Metabolômica/métodos , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Espectrometria de Massas em Tandem , Infarto Cerebral , Biomarcadores , Prolina , Cromatografia Líquida de Alta Pressão
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