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1.
Chem Commun (Camb) ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984894

RESUMO

A through-space charge transfer pyrene-based fluorophore has been developed for organic light-emitting devices (OLEDs). This material exhibits deep-blue fluorescence, bipolar characteristics, and anti-quenching behavior in the solid state. It proves to be an effective emitter for both doped and nondoped deep-blue OLEDs.

2.
Angew Chem Int Ed Engl ; : e202406677, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825572

RESUMO

The microtubule-associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau's engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse-mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid-modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p-tau) present two-state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid-tau interaction. The results indicate that p-tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease.

3.
Analyst ; 149(9): 2629-2636, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38563459

RESUMO

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.


Assuntos
Algoritmos , Movimento Celular , Rastreamento de Células , Rastreamento de Células/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos
4.
ACS Meas Sci Au ; 4(1): 76-80, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38404487

RESUMO

Reactions involving sulfhydryl groups play a critical role in maintaining the structure and function of proteins. However, traditional mechanistic studies have mainly focused on reaction rates and the efficiency in bulk solutions. Herein, we have designed a cysteine-mutated nanopore as a biological protein nanoreactor for electrochemical visualization of the thiol substitute reaction. Statistical analysis of characteristic current signals shows that the apparent reaction rate at the single-molecule level in this confined nanoreactor reached 1400 times higher than that observed in bulk solution. This substantial acceleration of thiol substitution reactions within the nanopore offers promising opportunities for advancing the design and optimization of micro/nanoreactors. Moreover, our results could shed light on the understanding of sulfhydryl reactions and the thiol-involved signal transduction mechanisms in biological systems.

5.
BMC Cancer ; 24(1): 253, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395798

RESUMO

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.


Assuntos
Desnutrição , Neoplasias Gástricas , Humanos , Caquexia/diagnóstico , Caquexia/etiologia , Prognóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Liderança , Velocidade de Caminhada , Desnutrição/complicações , Desnutrição/diagnóstico , Estado Nutricional , Força da Mão , Avaliação Nutricional
6.
Angew Chem Int Ed Engl ; 63(17): e202316551, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38411372

RESUMO

Single-entity electrochemistry is a powerful tool that enables the study of electrochemical processes at interfaces and provides insights into the intrinsic chemical and structural heterogeneities of individual entities. Signal processing is a critical aspect of single-entity electrochemical measurements and can be used for data recognition, classification, and interpretation. In this review, we summarize the recent five-year advances in signal processing techniques for single-entity electrochemistry and highlight their importance in obtaining high-quality data and extracting effective features from electrochemical signals, which are generally applicable in single-entity electrochemistry. Moreover, we shed light on electrochemical noise analysis to obtain single-molecule frequency fingerprint spectra that can provide rich information about the ion networks at the interface. By incorporating advanced data analysis tools and artificial intelligence algorithms, single-entity electrochemical measurements would revolutionize the field of single-entity analysis, leading to new fundamental discoveries.

7.
Mol Cell ; 84(3): 570-583.e7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215752

RESUMO

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts.


Assuntos
Antígenos CD , Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Adesão Celular , Microscopia Crioeletrônica , Complexo Glicoproteico GPIb-IX de Plaquetas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Antígenos CD/química , Antígenos CD/metabolismo
8.
Clin Exp Pharmacol Physiol ; 51(1): 10-16, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37806661

RESUMO

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three-dimensional computed tomography (3D-CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one-way valve were collected and analysed from 2017 to 2020. Three-dimensional-CT image analysis software system was used to analyse the distribution of low-density areas <950 Hounsfield units in both lungs pre- and post- BLVR. Meanwhile, all patients performed standard PFT pre- and post-operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%-47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D-CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Estudos Retrospectivos , Qualidade de Vida , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/etiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/cirurgia , Enfisema/diagnóstico por imagem , Enfisema/cirurgia , Enfisema/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005274

RESUMO

Colorectal cancer is a common malignant tumor in the digestive system, ranking third in incidence and second in the cause of death worldwide. In recent years, the incidence of colorectal cancer is on the rise, and the age of patients with colorectal cancer tends to be younger, with a heavy cancer burden. It is of great significance to prevent the occurrence, development, recurrence, and metastasis of colorectal cancer to reduce the incidence and mortality of colorectal cancer. Patriniae Herba has the effects of clearing heat, removing toxins, eliminating carbuncle, and discharging pus and shows good therapeutic efficacy on inflammatory bowel disease, digestive tract tumors, pelvic inflammation, gynecological tumor, and so on. Patriniae Herba is often used in the clinical treatment of colorectal cancer, but its mechanism of action is not clear. Modern studies have found that Patriniae Herba contains triterpenoids, saponins, iridoids, flavonoids, and other chemical components, with antioxidant, anti-tumor, anti-bacterial, and other pharmacological effects. The main anti-tumor components of Patriniae Herba are flavonoids. The analysis of network pharmacology and the spectrum-effect relationship has suggested that quercetin, luteolin, apigenin, isoorientin, and isovitexin play a major role in inhibiting the occurrence and development of colorectal cancer. In vivo and in vitro studies have shown that flavonoids in Patriniae Herba can play an anti-tumor role in various ways, such as preventing precancerous lesions of colorectal cancer, inhibiting the growth and proliferation of cancer cells, blocking cancer cell cycle, promoting cancer cell apoptosis, and reversing drug resistance of colorectal cancer. The oral availability of flavonoids is low. The gut is the main metabolic site of flavonoids in the body, its metabolic pathway is closely related to gut microbiota. This paper reviewed the anti-tumor mechanism of flavonoids and their influence on gut microbiota to provide a reference for further research on the mechanism of Patriniae Herba against colorectal cancer and its clinical application.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012705

RESUMO

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique, and then to clarify the mechanism of the two, as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group(CG), model group(MG), Aconiti Coreani Radix group(RA) and Typhonii Rhizoma group(RT). Except for the CG, ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG, rats in the other groups received whole powder suspension(0.586 mg·g-1) was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0, 3, 7 and 14. After the end of administration, the serum, brain tissue and urine of gerbils in each group were collected, and the rate of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC), and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO) in serum and brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), and the data were processed by multivariate statistical analysis, and differential metabolites were screened based on value of variable importance in the projection(VIP) of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG) database and Metaboanalyst 5.0. ResultCompared with the CG, the neurological deficit score was significantly increased in the MG(P<0.05), compared with the MG, the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d(P<0.05). Compared with the CG, the rate of cerebral infarction was significantly increased in the MG(P<0.05), compared with the MG, the rates of cerebral infarction in the RA and RT were significantly reduced(P<0.05). Compared with the CG, the levels of IL-6, TNF-α, and MDA in the serum and brain tissue of gerbils from the MG were significantly increased(P<0.05), and the levels of SOD, GSH and NO were significantly reduced(P<0.05). Compared with the MG, Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6, TNF-α and MDA, and up-regulated the levels of SOD, GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics, of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma, and could be used as potential biomarkers for both treatments in stroke gerbils, respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism, pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. In addition, Aconiti Coreani Radix could also regulate riboflavin metabolism, Typhonii Rhizoma could also regulate purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of pantothenate and coenzyme A, and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke, with Aconiti Coreani Radix having stronger effects. From the metabolomics results, the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism, oxidative stress and so on, while Typhonii Rhizoma mainly involve amino acid metabolism, lipid metabolism, energy metabolism, etc.

11.
Mikrochim Acta ; 191(1): 8, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38052768

RESUMO

Surface-enhanced Raman scattering (SERS) has been recognized as one of the most sensitive analytical methods by adsorbing the target of interest onto a plasmonic surface. Growing attention has been directed towards the fabrication of various substrates to broaden SERS applications. Among these, flexible SERS substrates, particularly paper-based ones, have gained popularity due to their easy-to-use features by full contact with the sample surface. Herein, we reviewed the latest advancements in flexible SERS substrates, with a focus on paper-based substrates. Firstly, it begins by introducing various methods for preparing paper-based substrates and highlights their advantages through several illustrative examples. Subsequently, we demonstrated the booming applications of these paper-based SERS substrates in abiotic and biological matrix detection, with particular emphasis on their potential application in clinical diagnosis. Finally, the prospects and challenges of paper-based SERS substrates in broader applications are discussed.

12.
World J Gastroenterol ; 29(34): 5038-5053, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37753370

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common clinical condition with a poor prognosis and few effective treatment options. Potent anticancer agents for treating HCC must be identified. Epigenetics plays an essential role in HCC tumorigenesis. Suberoylanilide hydroxamic acid (SAHA), the most common histone deacetylase inhibitor agent, triggers many forms of cell death in HCC. However, the underlying mechanism of action remains unclear. Family with sequence similarity 134 member B (FAM134B)-induced reticulophagy, a selective autophagic pathway, participates in the decision of cell fate and exhibits anticancer activity. This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death. AIM: To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death. METHODS: The viability, apoptosis, cell cycle, migration, and invasion of SAHA-treated Huh7 and MHCC97L cells were measured. Proteins related to the reticulophagy pathway, mitochondria-endoplasmic reticulum (ER) contact sites, intrinsic mitochondrial apoptosis, and histone acetylation were quantified using western blotting. ER and lysosome colocalization, and mitochondrial Ca2+ levels were characterized via confocal microscopy. The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization. Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region. RESULTS: After SAHA treatment, the proliferation of Huh7 and MHCC97L cells was significantly inhibited, and the migration and invasion abilities were greatly blocked in vitro. This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner. Following treatment with SAHA, ER-phagy was activated, thereby triggering autophagy-mediated cell death of HCC cells in vitro. Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region. Further, SAHA disturbed the Ca2+ homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells. Additionally, SAHA decreased the mitochondrial membrane potential levels, thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro. CONCLUSION: SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway, thereby enhancing HCC cell death.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Vorinostat/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Histonas , Lisina , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Morte Celular , Autofagia
13.
BMC Complement Med Ther ; 23(1): 304, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648989

RESUMO

INTRODUCTION: Allergic rhinitis is a global health problem that can potentially be managed through acupressure. Our clinical observations have identified Allergic Rhinitis Acupressure Therapeutic (ARAT) as a novel acupressure treatment acting on specific acupoints, which may enhance the effectiveness of acupressure. Therefore, we propose a three-arm randomized controlled trial will be conducted to investigate the efficacy and safety of ARAT for perennial allergic rhinitis (PAR). METHODS/DESIGN: In this trial, eligible 111 participants diagnosed with PAR will be randomly assigned to one of three groups: the ARAT group, the non-specific acupoints group, or the blank control group. The primary outcome will be the change in the total nasal symptom score, and the secondary outcomes will include: 1) changes in the scores of the standard version of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs); 2) acoustic rhinometry and anterior rhinomanometry; 3) changes in the scores of relief medication usage; 4) incidence of adverse events. Additionally, we will measure and compare the changes in cytokine levels (IL-5, IL-13, IFN-γ, and TSLP) in nasal secretions. The RQLQs and primary outcomes will be assessed at the beginning, middle, and end stages of the treatment period, with monthly follow-ups conducted over a total of three months. The secondary outcomes and biomarkers in nasal secretions will be measured at the beginning and end of the treatment period. Any adverse events or need for rescue medication will be carefully noted and recorded. DISCUSSION: This study may produce a new acupressure treatment prescription that is easy to learn, more targeted, and adaptable. This trial represents the first clinical investigation comparing ARAT treatment for PAR with the non-specific acupoints group and blank control group. Our data is expected to provide evidence demonstrating the safety and efficacy of ARAT for PAR patients, while also exploring the functional mechanism underlying ARAT treatment, moreover, the results offer valuable insights for healthcare professionals in managing PAR symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300072292. Registered on June 08, 2023.


Assuntos
Acupressão , Rinite Alérgica , Humanos , Qualidade de Vida , Mucosa Nasal , Rinite Alérgica/terapia , Pontos de Acupuntura , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Front Microbiol ; 14: 1071603, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275170

RESUMO

Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8-32 µg/mL in vitro, and the activity increased 2-8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it's a good antioxidant for host cells.

15.
Front Public Health ; 11: 1170085, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250088

RESUMO

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Quarentena , Estudos Retrospectivos , China/epidemiologia , Fatores de Risco
16.
Angew Chem Int Ed Engl ; 62(27): e202304023, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37115672

RESUMO

Disulfide bonds play an important role in thiol-based redox regulation. However, owing to the lack of analytical tools, little is known about how local O2 mediates the reversible thiol/disulfide cycle under protein confinement. In this study, a protein-nanopore inside a glove box is used to control local O2 for single-molecule reaction, as well as a single-molecule sensor for real-time monitoring of the reversible thiol/disulfide cycle. The results demonstrate that the local O2 molecules in protein nanopores could facilitate the redox cycle of disulfide formation and cleavage by promoting a higher fraction of effective reactant collisions owing to nanoconfinement. Further kinetic calculations indicate that the negatively charged residues near reactive sites facilitate proton-involved oxygen-induced disulfide cleavage under protein confinement. The unexpectedly strong oxidation ability of confined local O2 may play an essential role in cellular redox signaling and enzyme reactions.


Assuntos
Nanoporos , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Dissulfetos/química , Oxigênio , Proteínas/química , Oxirredução
17.
Research (Wash D C) ; 6: 0019, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37040505

RESUMO

Heart failure (HF), leading as one of the main causes of mortality, has become a serious public health issue with high prevalence around the world. Single cardiomyocyte (CM) metabolomics promises to revolutionize the understanding of HF pathogenesis since the metabolic remodeling in the human hearts plays a vital role in the disease progression. Unfortunately, current metabolic analysis is often limited by the dynamic features of metabolites and the critical needs for high-quality isolated CMs. Here, high-quality CMs were directly isolated from transgenic HF mice biopsies and further employed in the cellular metabolic analysis. The lipids landscape in individual CMs was profiled with a delayed extraction mode in time-of-flight secondary ion mass spectrometry. Specific metabolic signatures were identified to distinguish HF CMs from the control subjects, presenting as possible single-cell biomarkers. The spatial distributions of these signatures were imaged in single cells, and those were further found to be strongly associated with lipoprotein metabolism, transmembrane transport, and signal transduction. Taken together, we systematically studied the lipid metabolism of single CMs with a mass spectrometry imaging method, which directly benefited the identification of HF-associated signatures and a deeper understanding of HF-related metabolic pathways.

18.
Nanoscale ; 15(16): 7261-7266, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37038732

RESUMO

We developed a bipolar SiNx nanopore for the observation of single-molecule heterogeneous enzymatic dynamics. Single glucose oxidase was immobilized inside the nanopore and its electrocatalytic behaviour was real-time monitored via continuous recording of ionic flux amplification. The temporal heterogeneity in enzymatic properties and its spatial dynamic orientations were observed simultaneously, and these two properties were found to be closely correlated. We anticipate that this method offers new perspectives on the correlation of protein structure and function at the single-molecule level.


Assuntos
Nanoporos , Proteínas/química , Glucose Oxidase , Nanotecnologia , Íons
19.
Chem Soc Rev ; 52(8): 2596-2616, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36994760

RESUMO

Molecular structure conversion concomitant with mass transfer processes at the electrode-electrolyte interfaces plays a central role in energy electrochemistry. Mass spectrometry, as one of the most intuitive, sensitive techniques, provides the capability to collect transient intermediates and products and uncover reaction mechanisms and kinetics. In situ time-of-flight secondary ion electrochemical mass spectrometry with inherent high mass and spatiotemporal resolution has emerged as a promising strategy for investigating electrochemical processes at the electrode surface. This review illustrates the recent advancements in coupling time-of-flight secondary ion mass spectrometry and electrochemistry to visualize and quantify local dynamic electrochemical processes, identify solvated species distribution, and disclose hidden reaction pathways at the molecular level. Moreover, the key challenges in this field are further discussed to promote new applications and discoveries in operando studying the dynamic electrochemical interfaces of advanced energy systems.

20.
Chemistry ; 29(27): e202203919, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-36787024

RESUMO

Sequence-defined polymer is one of the most promising alternative media for high-density data storage. It could be used to alleviate the problem of insufficient storage capacity of conventional silicon-based devices for the explosively increasing data. To fulfil the goal of polymer data storage, suitable methods should be developed to accurately read and decode the information-containing polymers, especially for those composed by a combination of the natural and unnatural monomers. Nanopore-based approaches have become one of the most competitive analysis and sequencing techniques, which are expected to read both natural and synthetic polymers with single-molecule precision and monomeric resolution. Herein, this work emphasizes the advances being made in nanopore reading and decoding of information stored in the man-made polymers and DNA nanostructures, and discusses the challenges and opportunities towards the development and realization of high-density data storage.

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