RESUMO

Alcohols are the most commercially abundant, synthetically versatile and operationally convenient functional groups in organic chemistry. Therefore, a strategy that utilizes hydroxy-containing compounds to develop novel bond disconnection and formation process would achieve molecular diversity. Herein, a deconstructive strategy for the generation of quinoxalin-2(1H)-one derivatives has been developed from alcohol precursors via oxy-radical-induced ß-fragmentation. Additionally, 1,5-HAT and deoxygenation by P(III) along with oxy-radical were demonstrated as alternative pathways for this transformation. Furthermore, with the deep-seated reorganization of a few terpenes carbon framework, a unique activity with inhibition against the growth of pathogenic fungi was observed.

RESUMO

Cell sorting holds broad applications in fields such as early cancer diagnosis, cell differentiation studies, drug screening, and single-cell sequencing. However, achieving high-throughput and high-purity in label-free single-cell sorting is challenging. To overcome this issue, we propose a label-free, high-throughput, and high-accuracy impedance-activated cell sorting system based on impedance detection and dual membrane pumps. Leveraging the low-latency characteristics of FPGA, the system facilitates real-time dual-frequency single-cell impedance detection with high-throughput (5 × 104 cells per s) for HeLa, MDA-MB-231, and Jurkat cells. Furthermore, the system accomplishes low-latency (less than 0.3 ms), label-free, high-throughput (1000 particles per s) and high-accuracy (almost 99%) single-particle sorting using FPGA-based high-precision sort-timing prediction. In experiments with Jurkat and MDA-MB-231 cells, the system achieved a throughput of up to 1000 cells per s, maintaining a pre-sorting purity of 28.57% and increasing post-sorting purity to 97.09%. These findings indicate that our system holds significant potential for applications in label-free, high-throughput cell sorting.

RESUMO

MicroRNAs (miRNAs) have emerged as promising biomarkers for acute myocardial infarction (AMI). There is an urgent imperative to develop analytical methodologies capable of intelligently discerning multiple circulating miRNAs. Here, we present a dual miRNA detection platform for AMI using DNA logic gates coupled with an electrochemiluminescence (ECL) response. The platform integrates DNA truncated square pyramids as capture probes on gold-deposited electrodes, enabling precise quantification of miRNA associated with AMI. The cyclic enzymatic signal amplification principle of strand displacement amplification enhances the miRNA detection sensitivity. AND and OR logic gates have been successfully constructed, enabling intelligent identification of miRNAs in AMI. Calibration curves show strong linear correlations between ECL intensity and target miRNA concentration (10 fM to 10 nM), with excellent stability in consecutive measurements. When applied to clinical serum samples, the biosensor exhibits consistent performance, underscoring its reliability for clinical diagnostics. This innovative approach not only demonstrates DNA nanotechnology's potential in biosensing but also offers a promising solution for improving AMI diagnosis and prognosis through precise miRNA biomarker detection.

Assuntos

Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs , MicroRNAs/análise , MicroRNAs/sangue , Humanos , Técnicas Biossensoriais/métodos , DNA/química , Infarto do Miocárdio/diagnóstico , Ouro/química , Técnicas de Amplificação de Ácido Nucleico , Miocárdio/metabolismo , Miocárdio/química

RESUMO

The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Assuntos

Actinina , Antivirais , Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Replicação Viral , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Humanos , Animais , Antivirais/farmacologia , Actinina/genética , Actinina/metabolismo , Camundongos , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , COVID-19/virologia , COVID-19/genética , COVID-19/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Camundongos Transgênicos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA Viral/genética

RESUMO

Triplex DNA structures, formed when a third DNA strand wraps around the major groove of DNA, are key molecular regulators and genomic threats. However, the regulatory network governing triplex DNA dynamics remains poorly understood. Here we reveal the binding and functional repertoire of proteins that interact with triplex DNA through chemoproteomic profiling in living cells. We develop a chemical probe that exhibits exceptional specificity towards triplex DNA. By employing a co-binding-mediated proximity capture strategy, we enrich triplex DNA interactome for quantitative proteomics analysis. This enables the identification of a comprehensive list of proteins that interact with triplex DNA, characterized by diverse binding properties and regulatory mechanisms in their native chromatin context. As a demonstration, we validate DDX3X as an ATP-independent triplex DNA helicase to unwind substrates with a 5' overhang to prevent DNA damage. Overall, our study provides a valuable resource for exploring the biology and translational potential of triplex DNA.

RESUMO

Alzheimer's disease (AD), characterized by its incurable nature and prevalence among the elderly, has remained a focal point in medical research. Increasing evidence suggests that peroxynitrite (ONOO-) serves as a crucial biomarker for the diagnosis of AD. In this study, we present a novel, easily available, high-yield, and cost-effective near-infrared (NIR) fluorescent probe, CDCI-ONOO. This probe utilizes a coumarin-dicyanoisophorone conjugate as the fluorophore and diphenylphosphinic chloride as the recognition site, enabling the detection of ONOO- both in vitro and in vivo. Upon interaction with ONOO-, CDCI-ONOO exhibits a distinct maximum emission peak at 715 nm with a substantial Stokes shift of 184 nm. The probe demonstrates excellent selectivity and sensitivity (LOD = 144 nM), along with noticeable colorimetric and fluorescence changes after the reaction. Comprehensive analyses using high-performance liquid chromatography (HPLC), high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations confirm that the reaction with ONOO- restores the initially quenched Intramolecular Charge Transfer (ICT), resulting in the formation of CDCI-OH, a product that emitting fluorescence in the near-infrared region. Furthermore, we demonstrated the successful application of CDCI-ONOO for ONOO- detection in neuronal cells and imaging of ONOO- in the brains of mice. These findings underscore the potential of CDCI-ONOO as a near-infrared fluorescent probe for in vivo ONOO- detection, offering a significant avenue for advancing our understanding of AD pathology and diagnosis.

RESUMO

Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.

RESUMO

Pulmonary neuroendocrine cells (PNECs) are unique airway epithelial cells that blend neuronal and endocrine functions, acting as key sensors in the lung. They respond to environmental stimuli like allergens by releasing neuropeptides and neurotransmitters. PNECs stand out as the only lung epithelial cells innervated by neurons, suggesting a significant role in airway-nerve communication via direct neural pathways and hormone release. Pathological conditions such as asthma are linked to increased PNECs counts and elevated calcitonin gene-related peptide (CGRP) production, which may affect neuroprotection and brain function. CGRP is also associated with neurodegenerative diseases, including Parkinson's and Alzheimer's, potentially due to its influence on inflammation and cholinergic activity. Despite their low numbers, PNECs are crucial for a wide range of functions, highlighting the importance of further research. Advances in technology for producing and culturing human PNECs enable the exploration of new mechanisms and cell-specific responses to targeted therapies for PNEC-focused treatments.

RESUMO

BACKGROUND: Cervical cancer ranks as one of the most prevalent malignancies among women worldwide and poses a significant threat to health and quality of life. MCL1 is an antiapoptotic protein closely linked to tumorigenesis, drug-resistance and poor prognosis in various cancers. Sanggenon C, a natural flavonoid derived from Morus albal., exhibits multiple activities, including anti-oxidant, anti-inflammatory, antivirus, and antitumor properties. However, the molecular mechanisms by which Sanggenon C exerts antitumor effects on in cervical cancer remain unclear. PURPOSE: To investigate the oncogenic role of MCL1 and elucidate the antitumor activity of Sanggenon C, along with its molecular mechanisms, in cervical cancer. METHODS: In vitro, the effects of Sanggenon C on proliferation, the cell cycle, apoptosis, and autophagy were explored. Transcriptome sequencing was employed to analyze critical genes and pathways. The expression of genes or proteins was evaluated via immunofluorescence, qRT-PCR, immunohistochemistry, and Western blotting. To identify targets of Sanggenon C, various techniques such as clinical database analysis, molecular docking, cellular thermal shift assays, co-immunoprecipitation, and ubiquitination assays were utilized. Additionally, Xenograft mouse models were established to further investigate Sanggenon C as a novel MCL1 inhibitor and its anti-tumor activity in vivo. RESULTS: Our investigation reveals that Sanggenon C effectively inhibits cervical cancer cell proliferation both in vitro and in vivo. Furthermore, Sanggenon C induces endoplasmic reticulum stress and triggers protective autophagy via activation of the ATF4-DDIT3-TRIB3-AKT-MTOR signaling axis. Furthermore, Sanggenon C specifically targets MCL1 to exert its antitumor effects by modulating MCL1 protein stability through SYVN1-mediated ubiquitination. Notably, MCL1 overexpression attenuates the Sanggenon C-induced decrease in cell viability and apoptosis. Our study further characterizes the role of MCL1 in cisplatin resistance and identifies MCL1 as a promising target for Sanggenon C, which effectively inhibits proliferation and induces apoptosis in cisplatin-resistant cervical cancer cells. Importantly, combining Sanggenon C with an autophagy inhibitor represents a promising strategy to enhance therapeutic outcomes in cisplatin-resistant cervical cancer cells. CONCLUSION: Our findings demonstrates that Sanggenon C induces endoplasmic reticulum stress and highlights the potential of targeting MCL1 to exploit vulnerabilities in drug-resistant cervical cancer cells. Sanggenon C emerges as a promising therapeutic agent against MCL1-driven adaptive chemoresistance through disruption of autophagy and endoplasmic reticulum stress in cervical cancer.

Assuntos

Autofagia , Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático , Proteína de Sequência 1 de Leucemia de Células Mieloides , Neoplasias do Colo do Útero , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HeLa , Camundongos Endogâmicos BALB C , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Simulação de Acoplamento Molecular

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with all-cause mortality increasing globally. Dietary magnesium (Mg), an anti-inflammatory nutrient, has been proven to be associated with the all-cause mortality. The association of dietary Mg intake and all-cause mortality in RA patients remains unknown. The aim of this study was to assess the association between dietary Mg intake and all-cause mortality in RA patients. METHODS: RA patients were extracted from the NHANES 1999-2018, and followed for survival through December 31, 2019. Dietary Mg intake data were obtained from 24-h dietary recall interview. The association between dietary Mg intake and RA patients' all-cause mortality was explored based on weighted univariate and multivariate Cox proportional hazard models and described as absolute risk difference (ARD), hazard ratios (HRs) and 95% confidence intervals (CIs). This association was further explored in subgroup analyses based on different age, gender and body mass index (BMI). RESULTS: Totally 2,952 patients were included. Until 31 December 2019, a total of 825 deaths were documented. RA patients with higher dietary Mg intake had a 11.12% reduction of all-cause mortality (ARD=-11.12%; HR = 0.74, 95%CI: 0.56-0.99) in the fully adjusted model, especially in female (HR = 0.68, 95%CI: 0.47-0.98), aged < 65 years (HR = 0.59, 95%CI: 0.37-0.94) and BMI ≤ 30 kg/m2 (HR = 0.62, 95%CI: 0.42-0.91). CONCLUSION: RA patients who consumed adequate dietary Mg from diet as well as supplements may had a lower risk of all-cause mortality.

Assuntos

Artrite Reumatoide , Dieta , Magnésio , Inquéritos Nutricionais , Humanos , Artrite Reumatoide/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Magnésio/administração & dosagem , Idoso , Adulto , Modelos de Riscos Proporcionais , Causas de Morte , Mortalidade , Bases de Dados Factuais , Estados Unidos/epidemiologia , Índice de Massa Corporal

RESUMO

Transition-metal-catalyzed hydroarylation of unactivated alkenes via metal hydride hydrogen atom transfer (MHAT) is an attractive approach for the construction of C(sp2)-C(sp3) bonds. However, this kind of reaction focuses mainly on using reductive hydrosilane as a hydrogen donor. Here, a novel photoinduced Co/Ni-cocatalyzed Markovnikov hydroarylation of unactivated alkenes with aryl bromides using protons as a hydrogen source has been developed. This reaction represents the first example of photoinduced MHAT via a reductive route intercepting an organometallic coreactant. The key to this transformation was that the CoIII-H species was generated from the protonation of the CoI intermediate, and the formed CoIII-C(sp3) intermediate interacted with the organometallic coreactant rather than reacting with nucleophiles, a method which has been well developed in photoinduced Co-catalyzed MHAT reactions. This reaction is characterized by its high catalytic efficiency, construction of quaternary carbons, simple reaction conditions and expansion of the reactive mode of Co-catalyzed MHAT reactions via a reductive route. Moreover, this catalytic system could also be applied to complex substrates derived from glycosides.

RESUMO

Tenvermectin B (TVM-B) and five TVM-B analogs were produced by fermentation of a genetically engineered strain Streptomyces avermitilis HU02, and TVM-B is being developed as a new insecticide. Through 11 generations of resistance selection against TVM-B in the diamondback moth, Plutella xylostella, the median lethal concentration (LC50) was increased from 14.84 to 1213.73 mg L-1. The resistance to TVM-B in P. xylostella developed fast and its realized heritability was high (h2 = 0.2901 (F7), h2 = 0.4070 (F11)). However, the relative fitness was 0.6916 suggesting a fitness cost in the resistant strains. The fitness cost was partially explained by the upregulation of the detoxification enzyme activity by 2.15 folds in carboxylate esterase (CarE) and the gene expressions of ATP-binding cassette transporter gene (ABCC2) and the alpha subunit of the glutamate-gated chloride channel (GluCl) by 1.70- and 2.32 folds, respectively. The resistance was also explained by two points of mutations at the alpha subunit of the glutamate-gated chloride channel in the P. xylostella (PxGluClα) subunit in F11. However, there was little change in the binding affinity. These results provided helpful information for the mechanism study of TVM-B resistance and will be conducive to designing rational resistance management strategies in P. xylostella.

Assuntos

Resistência a Inseticidas , Inseticidas , Ivermectina , Mariposas , Animais , Mariposas/genética , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Mariposas/efeitos dos fármacos , Mariposas/enzimologia , Resistência a Inseticidas/genética , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Inseticidas/farmacologia , Aptidão Genética , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Larva/crescimento & desenvolvimento , Larva/genética , Larva/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo

RESUMO

The subgrade crushed-rocks of Gonghe-Yushu (Gongyu) Expressway in Qinghai Province are seriously weathered, resulting in a series of pavement diseases. Among the weathered crushed-rocks, the weathering degree of slate is particularly serious, and its physical and mechanical properties, weathering resistance and applicability are not clear. Therefore, this paper takes the slate in the subgrade crushed-rocks of Gongyu Expressway as the research object, and drills the core of the slate rock block to make a cylindrical standard sample, and uniaxial and triaxial compression tests, nuclear magnetic resonance tests, and electron probe micro-analysis tests were performed on it within 50 freeze-thaw cycles (FTC) under saturated conditions. According to the test results, the mass, longitudinal wave velocity, and strength of the slate specimens all decrease with the increase of the number of FTC, the cohesion ( C ) increases first and then decreases, and the change trend of internal friction angle (φ) is completely opposite to the cohesion. The FTC has an expansion effect on the pores of the slate specimens, and the microstructure of the rock particles on the specimen's surface is removed and becomes smooth. The results of mechanical tests are used in the Hoek-Brown (H-B) strength criterion, and a unified expression of the H-B criterion suitable for slate in permafrost regions is established. The above conclusions can provide some construction reference and maintenance of high-grade highways in cold regions.

RESUMO

Temperature has a profound influence on various neuromodulation processes and has emerged as a focal point. However, the effects of acute environmental temperature fluctuations on cultured cortical networks have been inadequately elucidated. To bridge this gap, we have developed a brain-on-a-chip platform integrating cortical networks and electrodeposited Pt/Ir modified microelectrode arrays (MEAs) with 3D-printed bear-shaped triple chambers, facilitating control of temperature transients. This innovative system administers thermal stimuli while concurrently monitoring neuronal activity, including spikes and local field potentials, from 60 microelectrodes (diameter: 30 µm; impedance: 9.34 ± 1.37 kΩ; and phase delay: -45.26 ± 2.85°). Temperature transitions of approximately ±10 °C/s were applied to cortical networks on MEAs via in situ perfusion within the triple chambers. Subsequently, we examined the spatiotemporal dynamics of the brain-on-a-chip under temperature regulation at both the group level (neuronal population) and their interactions (network dynamics) and the individual level (cellular activity). Specifically, we found that after the temperature reduction neurons enhanced the overall information transmission efficiency of the network through synchronous firing to compensate for the decreased efficiency of single-cell level information transmission, in contrast to temperature elevation. By leveraging the integration of high-performance MEAs with perfusion chambers, this investigation provides a comprehensive understanding of the impact of temperature on the spatiotemporal dynamics of neural networks, thereby facilitating future exploration of the intricate interplay between temperature and brain function.

Assuntos

Microeletrodos , Neurônios , Platina , Temperatura , Animais , Platina/química , Neurônios/fisiologia , Irídio/química , Córtex Cerebral/fisiologia , Galvanoplastia/métodos , Ratos

RESUMO

Probiotics have many beneficial physiological activities, but the poor stability during storage and gastrointestinal digestion limits their application. Therefore, in this study, a novel type of shell-core microbead for loading probiotics was prepared through high-precision concentric drop formation technology using gelatin as the shell material and lipids as the core material. The microbeads have a regular spherical structure, uniform size, low moisture content (<4%) and high probiotic activity (>9.0 log CFU/g). Textural testing showed that the hardness of the medium-chain triglyceride microbeads (MCTBs), cocoa butter replacer microbeads (CBRBs) and hydrogenated palm oil microbeads (HPOBs) increased gradually (319.65, 623.54, 711.41 g), but their springiness decreased (67.7, 43.3, 34.0%). Importantly, lipids with higher melting points contributed to the enhanced stability of probiotics during simulated digestion and storage. The viable probiotic counts of the HCTBs, CBRBs and HPOBs after being stored at 25 °C for 12 months were 8.01, 8.44, and 8.51 log CFU/g, respectively. In the simulated in vitro digestion process, the HPOBs resisted the destructive effects of digestive enzymes and gastric acid on probiotics, with a reduction in the probiotic viability of less than 1.5 log CFU/g. This study can provide new ideas for the preparation of intestinal delivery probiotic foods.

RESUMO

Chemical warfare agents primarily comprise organophosphorus nerve agents, saliva alkaloids, cyanides, and mustard gas. Exposure to these agents can result in severe respiratory effects, including spasms, edema, and increased secretions leading to breathing difficulties and suffocation. Protecting public safety and national security from such threats has become an urgent priority. Porous metal-organic framework (MOF) materials have emerged as promising candidates for the degradation of chemical warfare agents due to their large surface area, tunable pore size distribution, and excellent catalytic performance. Furthermore, combining MOFs with polymers can enhance their elasticity and processability and improve their degradation performance. In this review, we summarize the literature of the past five years on MOF-based composite materials and their effectiveness in degrading chemical warfare agents. Moreover, we discuss key factors influencing their degradation efficiency, such as MOF structure, pore size, and functionalization strategies. Furthermore, we highlight recent developments in the design of MOF-polymer composites, which offer enhanced degradation performance and stability for practical applications in CWA degradation. These composite materials exhibit good performance in degrading chemical warfare agents, playing a crucial role in protecting public safety and maintaining national security. We can expect to see more breakthroughs in the application of metal-organic framework porous materials for degrading chemical warfare agents. It is hoped that these innovative materials will play a positive role in achieving social stability and security.

RESUMO

Background: The incidence of postoperative acute kidney injury (AKI) is high due to insufficient perfusion in patients with heart failure. Heart failure patients with preserved ejection fraction (HFpEF) have strong heterogeneity, which can obtain more accurate results. There are few studies for predicting AKI after coronary artery bypass grafting (CABG) in HFpEF patients especially using machine learning methodology. Methods: Patients were recruited in this study from 2018 to 2022. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The machine learning methods adopted included logistic regression, random forest (RF), extreme gradient boosting (XGBoost), gaussian naive bayes (GNB), and light gradient boosting machine (LGBM). We used the receiver operating characteristic curve (ROC) to evaluate the performance of these models. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were utilized to compare the prediction model. Results: In our study, 417 (23.6%) patients developed AKI. Among the five models, random forest was the best predictor of AKI. The area under curve (AUC) value was 0.834 (95% confidence interval (CI) 0.80-0.86). The IDI and NRI was also better than the other models. Ejection fraction (EF), estimated glomerular filtration rate (eGFR), age, albumin (Alb), uric acid (UA), lactate dehydrogenase (LDH) were also significant risk factors in the random forest model. Conclusions: EF, eGFR, age, Alb, UA, LDH are independent risk factors for AKI in HFpEF patients after CABG using the random forest model. EF, eGFR, and Alb positively correlated with age; UA and LDH had a negative correlation. The application of machine learning can better predict the occurrence of AKI after CABG and may help to improve the prognosis of HFpEF patients.

RESUMO

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

Assuntos

DNA Viral , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , DNA Viral/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , RNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Antivirais/uso terapêutico

RESUMO

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.

Assuntos

Ouro , Microeletrodos , Rede Nervosa , Neurônios , Ouro/química , Animais , Neurônios/fisiologia , Rede Nervosa/fisiologia , Comunicação Celular , Ratos , Células Cultivadas

RESUMO

Single-atom catalysts have emerged as cutting-edge hotspots in the field of material science owing to their excellent catalytic performance brought about by well-defined metal single-atom sites (M SASs). However, huge challenges still lie in achieving the rational design and precise synthesis of M SASs. Herein, we report a novel synthesis strategy based on the hetero-charge coupling effect (HCCE) to prepare M SASs loaded on N and S co-doped porous carbon (M1/NSC). The proposed strategy was widely applied to prepare 17 types of M1/NSC composed of single or multi-metal with the integrated regulation of the coordination environment and electronic structure, exhibiting good universality and flexible adjustability. Furthermore, this strategy provided a low-cost method of efficiently synthesizing M1/NSC with high yields, that can produce more than 50 g catalyst at one time, which is key to large-scale production. Among various as-prepared unary M1/NSC (M can be Fe, Co, Ni, V, Cr, Mn, Mo, Pd, W, Re, Ir, Pt, or Bi) catalysts, Fe1/NSC delivered excellent performance for electrocatalytic nitrate reduction to NH3 with high NH3 Faradaic efficiency of 86.6 % and high NH3 yield rate of 1.50 mg h-1 mgcat. -1 at -0.6 V vs. RHE. Even using Fe1/NSC as a cathode in a Zn-nitrate battery, it exhibited a high open circuit voltage of 1.756 V and high energy density of 4.42 mW cm-2 with good cycling stability.