RESUMO
N6 -methyladenosine (m6 A) in messenger RNA (mRNA) regulates immune cells in homeostasis and in response to infection and inflammation. The function of the m6 A reader YTHDF2 in the tumor microenvironment (TME) in these contexts has not been explored. We discovered that the loss of YTHDF2 in regulatory T (Treg) cells reduces tumor growth in mice. Deletion of Ythdf2 in Tregs does not affect peripheral immune homeostasis but leads to increased apoptosis and impaired suppressive function of Treg cells in the TME. Elevated tumor necrosis factor (TNF) signaling in the TME promotes YTHDF2 expression, which in turn regulates NF-κB signaling by accelerating the degradation of m6 A-modified transcripts that encode NF-κB-negative regulators. This TME-specific regulation of Treg by YTHDF2 points to YTHDF2 as a potential target for anti-cancer immunotherapy, where intratumoral Treg cells can be targeted to enhance anti-tumor immune response while avoiding Treg cells in the periphery to minimize undesired inflammations.
Assuntos
NF-kappa B , Neoplasias , Camundongos , Animais , NF-kappa B/genética , Neoplasias/genética , Transdução de Sinais , Imunoterapia , Inflamação , Microambiente TumoralRESUMO
Enzymatic reaction kinetics are central in analyzing enzymatic reaction mechanisms and target-enzyme optimization, and thus in biomanufacturing and other industries. The enzyme turnover number (kcat) and Michaelis constant (Km), key kinetic parameters for measuring enzyme catalytic efficiency, are crucial for analyzing enzymatic reaction mechanisms and the directed evolution of target enzymes. Experimental determination of kcat and Km is costly in terms of time, labor, and cost. To consider the intrinsic connection between kcat and Km and further improve the prediction performance, we propose a universal pretrained multitask deep learning model, MPEK, to predict these parameters simultaneously while considering pH, temperature, and organismal information. Through testing on the same kcat and Km test datasets, MPEK demonstrated superior prediction performance over the previous models. Specifically, MPEK achieved the Pearson coefficient of 0.808 for predicting kcat, improving ca. 14.6% and 7.6% compared to the DLKcat and UniKP models, and it achieved the Pearson coefficient of 0.777 for predicting Km, improving ca. 34.9% and 53.3% compared to the Kroll_model and UniKP models. More importantly, MPEK was able to reveal enzyme promiscuity and was sensitive to slight changes in the mutant enzyme sequence. In addition, in three case studies, it was shown that MPEK has the potential for assisted enzyme mining and directed evolution. To facilitate in silico evaluation of enzyme catalytic efficiency, we have established a web server implementing this model, which can be accessed at http://mathtc.nscc-tj.cn/mpek.
Assuntos
Aprendizado Profundo , Enzimas , Cinética , Enzimas/metabolismo , Enzimas/química , Algoritmos , Biologia Computacional/métodosRESUMO
RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other RNA systems, such as siRNA and CRISPR technologies, the ribozyme tools are still far from broad applications on RNAi due to their poor performance in the cellular context. In this work, we report an efficient RNAi tool based on chemically modified hammerhead ribozyme (HHR). By the introduction of an intramolecular linkage into the minimal HHR to reconstruct the distal interaction within the tertiary ribozyme structure, this cross-linked HHR exhibits efficient RNA substrate cleavage activities with almost no sequence constraint. Cellular experiments suggest that both exogenous and endogenous RNA expression can be dramatically knocked down by this HHR tool with levels comparable to those of siRNA. Unlike the widely applied protein-recruiting RNA systems (siRNA and CRISPR), this ribozyme tool functions solely on RNA itself with great simplicity, which may provide a new approach for gene manipulation in both fundamental and translational studies.
Assuntos
RNA Catalítico , RNA Catalítico/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Processamento de Proteína Pós-Traducional , Conformação de Ácido NucleicoRESUMO
The present study is aimed to address the challenge of wound age estimation in forensic science by identifying reliable genetic markers using low-cost and high-precision second-generation sequencing technology. A total of 54 Sprague-Dawley rats were randomly assigned to a control group or injury groups, with injury groups being further divided into time points (4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, and 32 h after injury, n = 6) to establish rat skeletal muscle contusion models. Gene expression data were obtained using second-generation sequencing technology, and differential gene expression analysis, weighted gene co-expression network analysis (WGCNA) and time-dependent expression trend analysis were performed. A total of six sets of biomarkers were obtained: differentially expressed genes at adjacent time points (127 genes), co-expressed genes most associated with wound age (213 genes), hub genes exhibiting time-dependent expression (264 genes), and sets of transcription factors (TF) corresponding to the above sets of genes (74, 87, and 99 genes, respectively). Then, random forest (RF), support vector machine (SVM) and multilayer perceptron (MLP), were constructed for wound age estimation from the above gene sets. The results estimated by transcription factors were all superior to the corresponding hub genes, with the transcription factor group of WGCNA performed the best, with average accuracy rates of 96% for three models' internal testing, and 91.7% for the highest external validation. This study demonstrates the advantages of the indicator screening system based on second-generation sequencing technology and transcription factor level for wound age estimation.
Assuntos
Contusões , Músculo Esquelético , Ratos Sprague-Dawley , Animais , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Contusões/genética , Fatores de Tempo , Máquina de Vetores de Suporte , Sequenciamento de Nucleotídeos em Larga Escala , Ratos , Perfilação da Expressão Gênica , Marcadores Genéticos , Masculino , Genética Forense/métodosRESUMO
BACKGROUND: The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population. METHODS: A total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as "cases", and the mild and moderate patients were defined as "control". Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform. RESULTS: IFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008-0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746-8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045-15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant. CONCLUSION: Our study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.
Assuntos
COVID-19 , Fatores de Transcrição Forkhead , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Anticorpos Neutralizantes , COVID-19/genética , COVID-19/metabolismo , Fatores de Transcrição Forkhead/genética , Genótipo , Haplótipos , Interferons/metabolismo , Proteínas de Resistência a Myxovirus/metabolismoRESUMO
Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation. Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA. Here, we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-α and IL-6 by inhibiting macrophage M1 phenotype. Mechanistically, KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB into the nucleus. Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice. Consistently, KOR administration suppresses the expressions of M1 macrophage markers and the NF-κB pathway in the synovium of the knee. Collectively, our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.
Assuntos
Osteoartrite , Receptores Opioides kappa , Sinovite , Idoso , Animais , Humanos , Camundongos , Artralgia/metabolismo , Macrófagos/metabolismo , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Dor/metabolismo , Receptores Opioides kappa/metabolismo , Sinovite/metabolismoRESUMO
SKI-349 is a novel sphingosine kinases (SPHK) inhibitor with anti-tumor effects. This study aimed to assess the effect of SKI-349 on cell biological behaviors, downstream pathways, and its synergistic effect with sorafenib in hepatocellular carcinoma (HCC). HCC cell lines (Huh7 and Hep3B) were treated with SKI-349 at concentrations of 1, 2, 4, or 8 µM. Then, SPHK1/2 activity, cell viability, proliferation, apoptosis, invasion, and protein expressions of phosphorylated-protein kinase B (p-AKT), AKT, phosphorylated-mammalian target of rapamycin (p-mTOR) and mTOR were detected. Combination index values of SKI-349 (0, 1, 2, 4, or 8 µM) and sorafenib (0, 2.5, 5, 10, or 20 µM) were calculated. SKI-349 decreased the relative SPHK1 and SPHK2 activity compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Meanwhile, SKI-349 reduced cell viability, 5-ethynyl-2'-deoxyuridine (EdU) positive cells, and invasive cells, while it increased apoptotic cells compared to blank control in a dose-dependent manner in Huh7 and Hep3B cell lines. Based on the western blot assay, SKI-349 decreased the ratio of p-AKT to AKT and that of p-mTOR to mTOR compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Additionally, SKI-349 combined with sorafenib declined cell viability with concentration gradient effects compared to SKI-349 sole treatment, and they had synergistic cytotoxic effects in Huh7 and Hep3B cell lines. SKI-349 suppresses SPHK1 and SPHK2 activity, cell viability, invasion, and AKT/mTOR signaling pathway, as well as exhibits a synergistic cytotoxic effect with sorafenib in HCC.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Esfingosina/farmacologia , Esfingosina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sobrevivência Celular , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Linhagem Celular Tumoral , Transdução de Sinais , Antineoplásicos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/uso terapêutico , Apoptose , Proliferação de CélulasRESUMO
Aim: To explore the influence of online and offline mixed teaching modes based on TPACK on theoretical knowledge and comprehensive ability of tumor gynecology postgraduates. Methods: In this study, a prospective randomized controlled study model was used to select 60 masters of oncology and gynecology who were interned in the Affiliated Hospital of the First Affiliated Hospital of Bengbu Medical College from September 2019 to April 2022 as the research objects. They were divided into a study group and a control group by random number table, with 30 cases in each group. The control group adopted the traditional teaching mode, while the study group adopted the mixed online and offline teaching mode based on TPACK to implement the teaching. The knowledge mastery, problem analysis ability and total ability of the two groups were compared before and after the practice. Results: After the practice, the scores of theoretical knowledge, clinical operation skills and case analysis ability of both groups were improved compared with those before the practice, and the scores of the study group were higher than those of the control group (P < .05). After practice, the scores of problem analysis and clinical work competence in both groups were significantly higher than those before practice, and the study group was higher than the control group (P < .05). After practice, the scores of professional technical knowledge, doctor-patient communication ability, clinical operation skill, disease observation ability and clinical first-aid ability of both groups were improved compared with those before practice, and the scores of the study group were higher than those of the control group (P < .05). Conclusion: In clinical teaching, the online and offline mixed teaching mode based on TPACK has obvious effects on improving the theoretical and clinical operation level of tumor gynecology postgraduates and the total ability of medical staff.
RESUMO
TRPV1 channel agonists and antagonists, which have powerful analgesic effects without the addictive qualities associated with traditional analgesics, have become a focus area for the development of novel analgesics. In this study, quantitative structure-activity relationship (QSAR) models for three bioactive endpoints (Ki, IC50, and EC50) were successfully constructed using four machine learning algorithms: SVM, Bagging, GBDT, and XGBoost. These models were based on 2922 TRPV1 modulators and incorporated four types of molecular descriptors: Daylight, E-state, ECFP4, and MACCS. After the rigorous five-fold cross-validation and external test set validation, the optimal models for the three endpoints were obtained. For the Ki endpoint, the Bagging-ECFP4 model had a Q2 value of 0.778 and an R2 value of 0.780. For the IC50 endpoint, the XGBoost-ECFP4 model had a Q2 value of 0.806 and an R2 value of 0.784. For the EC50 endpoint, the SVM-Daylight model had a Q2 value of 0.784 and an R2 value of 0.809. These results demonstrate that the constructed models exhibit good predictive performance. In addition, based on the model feature importance analysis, the influence between substructure and biological activity was also explored, which can provide important theoretical guidance for the efficient virtual screening and structural optimization of novel TRPV1 analgesics. And subsequent studies on novel TRPV1 modulators will be based on the feature substructures of the three endpoints.
Assuntos
Algoritmos , Confiabilidade dos Dados , Aprendizado de Máquina , Relação Quantitativa Estrutura-Atividade , Analgésicos/farmacologiaRESUMO
OBJECTIVE: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. METHODS: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. RESULTS: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. CONCLUSIONS: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.
Assuntos
Artrite Reumatoide , Ferroptose , Camundongos , Animais , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Artrite Reumatoide/metabolismo , Células Cultivadas , Proliferação de CélulasRESUMO
Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.
Assuntos
Doença da Artéria Coronariana , Trombose Coronária , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/complicações , Placa Aterosclerótica/patologia , Trombose Coronária/complicações , Trombose Coronária/patologia , Fatores de Risco , Doença da Artéria Coronariana/complicações , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologiaRESUMO
Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR-Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA-based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis-related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.
Assuntos
RNA Catalítico , Animais , RNA Catalítico/metabolismo , RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Apoptose , Transdução de Sinais , Redes Reguladoras de Genes , Mamíferos/metabolismoRESUMO
Signal transduction from non-nucleic acid ligands (small molecules and proteins) to structural changes of nucleic acids plays a crucial role in both biomedical analysis and cellular regulations. However, how to bridge between these two types of molecules without compromising the expandable complexity and programmability of the nucleic acid nanomachines is a critical challenge. Compared with the previously most widely applied transduction strategies, we review the latest advances of a kinetically controlled approach for ligand-oligonucleotide transduction in this Concept article. This new design works through an intrinsic conformational alteration of the nucleic acid aptamer upon the ligand binding as a governing factor for nucleic acid strand displacement reactions. The functionalities and applications of this transduction system as a ligand converter on biosensing and DNA computation are described and discussed. Furthermore, we propose some potential scenarios for utilization of this ligand transduction design to regulate gene expression through synthetic RNA switches in the cellular contexts. Finally, future perspectives regarding this ligand-oligonucleotide transduction platform are also discussed.
Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Ácidos Nucleicos/química , Ligantes , Proteínas , OligonucleotídeosRESUMO
With the rapid development of the backbone network rates, there has been a gradual increase in channel spacing and bandwidth. The C&L band ultra-broad bandwidth array waveguide gratings (AWG) of 60-channel 100â GHz channel spacing are designed and fabricated based on silica waveguide. A new parabolic design is used to achieve ultra-broad bandwidth and good spectrum. For the C band ultra-broad bandwidth AWG, the peak insertion loss, uniformity, 0.5â dB bandwidth, 1â dB bandwidth and 3â dB bandwidth are 2.98â dB, 0.36â dB, 0.614â nm, 0.721â nm and 0.937â nm, respectively. For the L band ultra-broad bandwidth AWG, the peak insertion loss, uniformity, 0.5â dB bandwidth, 1â dB bandwidth and 3â dB bandwidth are 2.91â dB, 0.27â dB, 0.560â nm, 0.665â nm and 0.879â nm, respectively. To ensure ultra-broad bandwidth AWG operation at different temperatures, a temperature control circuit is integrated into the packaging design. It has been observed that the performances remain virtually unchanged within the temperature range of -15 to 65 degree. The ultra-broadband AWGs have been successfully tested to transmit 96 Gbaud signals and can be applied to 600â G/800â G backbone network transmission. By using the C&L ultra-broad bandwidth AWGs of 60-channel 100â GHz channel spacing, the total transmission speed over a single-mode fiber can reach 72Tbps/96Tbps.
RESUMO
Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.
Assuntos
Nanopartículas Metálicas , Agentes Neurotóxicos , Ouro/química , Carbamatos , Espectrometria de Fluorescência/métodos , China , Nanopartículas Metálicas/química , Limite de DetecçãoRESUMO
During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.
Assuntos
Córtex Visual , Astrócitos , Período Crítico Psicológico , Plasticidade Neuronal/fisiologia , Córtex Visual Primário , Privação Sensorial/fisiologia , Córtex Visual/fisiologiaRESUMO
A novel active Ce-doped Ti4O7 (Ti/Ti4O7-Ce) electrode was prepared and evaluated for improvement of the refractory pollutants degradation efficiency in Electrochemical advanced oxidation processes (EAOPs). The results showed that the addition of Ce in Ti/Ti4O7 electrode leading to great impact on â¢OH generation rate and electrode stability compared to pristine Ti/Ti4O7 electrode. Ti/Ti4O7-Ce electrode presented efficient oxidation capacity for pharmaceutical pollutant atenolol (ATL) in EAOPs, which could be attributed to the improvement of indirect oxidation mediated by electro-generated â¢OH, as the amount of â¢OH production was 16.5% higher than that in Ti/Ti4O7 within 120 min. The operational conditions greatly influenced the ATL degradation. The degradation efficiency of ATL increased as the current density, the degradation efficiency reached 100% under pH 4, but it just removed 81% of ATL under pH 10 after 120 min treatment. Results also suggested that the inhibiting effect from the ATL degradation was mostly associated with the decreased oxidation capacity induced by water hardness and natural organic matter (NOM). It displayed a satisfactory durability after 40 cycles of experimental detections in this research. The results of study suggested that Ti/Ti4O7-Ce was a promising electrode for the efficient degradation of PPCPs-polluted wastewater and provided constructive suggestion for the refractory pollutants of EAOPs.
Assuntos
Atenolol , Poluentes Químicos da Água , Titânio , Poluentes Químicos da Água/análise , Eletrodos , Oxirredução , Preparações FarmacêuticasRESUMO
Purpose: The effectiveness of inactivated vaccines against acute respiratory syndrome coronavirus 2 (SARSCoV2), the causative agent of coronavirus disease 2019 (COVID-19), has become a global concern. Hence, the aim of this study was to evaluate vaccine safety and to assess immune responses in individuals with chronic respiratory disease (CRD) following a two-dose vaccination. Methods: The study cohort included 191 participants (112 adult CRD patients and 79 healthy controls [HCs]) at least 21 (range, 21-159) days after a second vaccination. Frequencies of memory B cells (MBCs) subsets and titers of SARS-CoV-2 neutralizing antibodies (NAbs) and anti-receptor binding domain (RBD) IgG antibodies (Abs) were analyzed. Results: As compared to the HCs, CRD patients had lower seropositivity rates and titers of both anti-RBD IgG Abs and NAbs, in addition to lower frequencies of RBD-specific MBCs (all, p < 0.05). At 3 months, CRD patients had lower seropositivity rates and titers of anti-RBD IgG Abs than the HCs (p < 0.05). For CoronaVac, the seropositivity rates of both Abs were lower in patients with old pulmonary tuberculosis than HCs. For BBIBP-CorV, the seropositivity rates of CoV-2 NAbs were lower in patients with chronic obstructive pulmonary disease than HCs (all, p < 0.05). Meanwhile, there was no significant difference in overall adverse events between the CRD patients and HCs. Univariate and multivariate analyses identified the time interval following a second vaccination as a risk factor for the production of anti-RBD IgG Abs and CoV-2 NAbs, while the CoronaVac had a positive effect on the titers of both Abs. Female was identified as a protective factor for CoV-2 NAb levels. Conclusion: Inactivated COVID-19 vaccines were safe and well tolerated by CRD patients but resulted in lower Ab responses and the frequencies of RBD-specific MBCs. Therefore, CRD patients should be prioritized for booster vaccinations.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Feminino , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , População do Leste Asiático , Imunidade , Imunoglobulina G , SARS-CoV-2 , Eficácia de Vacinas , Imunogenicidade da Vacina , Doenças Respiratórias/imunologia , Doença CrônicaRESUMO
A 90° optical hybrid (OH) based on a 4×4 multimode interference (MMI) coupler is characterized and analyzed using the silica-based planar light circuit. The OH is designed to be polarization-insensitive with an extremely low polarization-dependent loss (<0.18d B) and phase error (w i t h i n±1.3∘). The fabricated chip exhibits an excess loss of 3.4 dB and 3.8 dB for TE and TM polarizations at 1550 nm. The measured phase error is w i t h i n±7.2∘ over 50 nm in the C+L band with a polarization-dependent error w i t h i n±3.5∘. The fabrication tolerance of the MMI width and waveguide sidewall angle is analyzed, which can well explain the deviation from the theoretical calculation.
RESUMO
In recent years, the widespread application of artificial intelligence algorithms in protein structure, function prediction, and de novo protein design has significantly accelerated the process of intelligent protein design and led to many noteworthy achievements. This advancement in protein intelligent design holds great potential to accelerate the development of new drugs, enhance the efficiency of biocatalysts, and even create entirely new biomaterials. Protein characterization is the key to the performance of intelligent protein design. However, there is no consensus on the most suitable characterization method for intelligent protein design tasks. This review describes the methods, characteristics, and representative applications of traditional descriptors, sequence-based and structure-based protein characterization. It discusses their advantages, disadvantages, and scope of application. It is hoped that this could help researchers to better understand the limitations and application scenarios of these methods, and provide valuable references for choosing appropriate protein characterization techniques for related research in the field, so as to better carry out protein research.