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Modulating the electronic structure of catalysts to effectively couple the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is essential for developing high-efficiency anion exchange membrane water electrolyzer (AEMWE). Herein, a coral-like nanoarray composed of nanosheets through the synergistic layering effect of cobalt and the 1D guiding of vanadium is synthesized, which promotes extensive contact between the active sites and electrolyte. The HER and OER activities can be enhanced by modulating the electronic structure through nitridation and phosphorization, respectively, enhancing the strength of metal-H bond to optimize hydrogen adsorption and facilitating the proton transfer to improve the transformation of oxygen-containing intermediates. Resultantly, the AEMWE achieves a current density of 500 mA cm-2 at 1.76 V for 1000 h in 1.0 M KOH at 70 °C. The energy consumption is 4.21 kWh Nm-3 with the producing hydrogen cost of $0.93 per kg H2. Operando synchrotron radiation and Bode phase angle analyses reveal that during the high-energy consumed OER, the dissolution of vanadium species transforms distorted Co-O octahedral into regular octahedral structures, accompanied by a shortening of the Co-Co bond length. This structural evolution facilitates the formation of oxygen intermediates, thus accelerating the reaction kinetics.
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BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.
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Biomarcadores , Glicemia , Doenças Cardiovasculares , Causas de Morte , Diabetes Mellitus , Resistência à Insulina , Inquéritos Nutricionais , Triglicerídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/metabolismo , Medição de Risco , Triglicerídeos/sangue , Biomarcadores/sangue , Estudos Transversais , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Fatores de Tempo , Prognóstico , Idoso , Adulto , Estados Unidos/epidemiologia , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma known for its propensity to metastasize to the lymph nodes and typically has an unfavorable prognosis. Currently, surgical resection is the primary treatment for localized CCS, while radiotherapy and chemotherapy are preferred for metastatic cases. The roles of adjuvant chemotherapy, radiotherapy, and lymph node dissection are controversial. Although immunotherapy has emerged as a promising avenue in CCS treatment research, there are no established clinical standards for postoperative follow-up. This editorial discusses a recent article by Liu et al, with a focus on current diagnostic modalities, treatment approaches, and the challenging prognosis associated with CCS. Our aim is to underscore the importance of long-term patient follow-up in CCS management.
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Recent experiments reported that quantum Hall chiral edge state-mediated Josephson junctions (chiral Josephson junctions) could exhibit Fraunhofer oscillations with a periodicity of either h/e [Vignaud et al., Nature (London) 624, 545 (2023)NATUAS0028-083610.1038/s41586-023-06764-4] or h/2e [Amet et al., Science 352, 966 (2016)SCIEAS0036-807510.1126/science.aad6203]. While the h/e-periodic component of the supercurrent had been anticipated theoretically before, the emergence of the h/2e periodicity is still not fully understood. In this Letter, we systematically study the Fraunhofer oscillations of chiral Josephson junctions. In chiral Josephson junctions, the chiral edge states coupled to the superconductors become chiral Andreev edge states. We find that in short junctions, the coupling of the chiral Andreev edge states can trigger the h/2e-magnetic flux periodicity. Our theory resolves the important puzzle concerning the appearance of the h/2e periodicity in chiral Josephson junctions. Furthermore, we explain that when the chiral Andreev edge states couple, a pair of localized Majorana zero modes appear at the ends of the Josephson junction, which are robust and independent of the phase difference between the two superconductors. As the h/2e periodicity and the Majorana zero modes have the same physical origin in the wide junction limit, the Fraunhofer oscillation period could be useful in identifying the regime with Majorana zero modes.
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The sluggish kinetics of the oxygen evolution reaction (OER) in alkaline water electrolysis remains a significant challenge for developing high-efficiency electrocatalytic systems. In this study, we present a three-dimensional, micrometer-sized iridium oxide (IrO2)-decorated cobalt carbonate hydroxide (IrO2-P-CoCH) electrocatalyst, which is engineered in situ on a carbon cloth (CC) substrate pretreated with atmospheric-pressure dielectric barrier discharge (DBD) plasma (PCC). The electrocatalyst features petal-like structures composed of nanosized rods, providing abundant reactive areas and sites, including the oxygen vacancy caused by the air-DBD plasma. As a result, the IrO2-P-CoCH/PCC electrocatalyst demonstrates an outstanding OER performance, with overpotentials of only 190 and 300 mV required to achieve current densities of 10 mA cm-2 (j10) and 300 mA cm-2 (j300), respectively, along with a low Tafel slope of 48.1 mV dec-1 in 1.0 M KOH. Remarkably, benefiting from rich active sites exposed on the IrO2-P-CoCH (Ir) heterostructure, the synergistic effect between IrO2 and CoCH enhances the charge delivery rates, and the IrO2-P-CoCH/PCC exhibits a superior electrocatalytic activity at a high current density (300 mV/j300) compared to the commercial benchmarked RuO2/PCC (470 mV/j300). Furthermore, the IrO2-P-CoCH/PCC electrocatalyst shows exceptional OER stability, with a mere 1.3% decrease with a current density of j10 for 100 h testing, surpassing most OER catalysts based on CC substrates. This work introduces a novel approach for designing high-performance OER electrocatalysts on flexible electrode substrates.
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The functional neurons are basic building blocks of the nervous system and are responsible for transmitting information between different parts of the body. However, it is less known about the interaction between the neuron and the field. In this work, we propose a novel functional neuron by introducing a flux-controlled memristor into the FitzHugh-Nagumo neuron model, and the field effect is estimated by the memristor. We investigate the dynamics and energy characteristics of the neuron, and the stochastic resonance is also considered by applying the additive Gaussian noise. The intrinsic energy of the neuron is enlarged after introducing the memristor. Moreover, the energy of the periodic oscillation is larger than that of the adjacent chaotic oscillation with the changing of memristor-related parameters, and same results is obtained by varying stimuli-related parameters. In addition, the energy is proved to be another effective method to estimate stochastic resonance and inverse stochastic resonance. Furthermore, the analog implementation is achieved for the physical realization of the neuron. These results shed lights on the understanding of the firing mechanism for neurons detecting electromagnetic field.
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Consensus and synchronous firing in neural activities are relative to the physical properties of synaptic connections. For coupled neural circuits, the physical properties of coupling channels control the synchronization stability, and transient period for keeping energy diversity. Linear variable coupling results from voltage coupling via linear resistor by consuming certain Joule heat, and electric synapse coupling between neurons derives from gap junction connection under special electrophysiological condition. In this work, a voltage-controlled electric component with quadratic relation in the i-v (current-voltage) is used to connect two neural circuits composed of two variables. The energy function obtained by using Helmholtz theorem is consistent with the Hamilton energy function converted from the field energy in the neural circuit. Chaotic signals are encoded to approach a mixed signal within certain frequency band, and then its amplitude is adjusted to excite the neuron for detecting possible occurrence of nonlinear resonance. External stimuli are changed to trigger different firing modes, and nonlinear coupling activates changeable coupling intensity. It is confirmed that nonlinear coupling behaves functional regulation as hybrid synapse, and the synchronization transition between neurons can be controlled for reaching possible energy balance. The nonlinear coupling is helpful to keep energy diversity and prevent synchronous bursting because positive and negative feedback is switched with time. As a result, complete synchronization is suppressed and phase lock is controlled between neurons with energy diversity.
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Simultaneous enhancement of free excitons (FEs) emission and self-trapped excitons (STEs) emission remains greatly challenging because of the radiative pathway competition. Here, a significant fluorescence improvement, associated with the radiative recombination of both FEs and STEs is firstly achieved in an unconventional ACI-type hybrid perovskite, (ACA)(MA)PbI4 (ACA=acetamidinium) crystals with {PbI6} octahedron units, through hydrostatic pressure processing. Note that (ACA)(MA)PbI4 exhibits a 91.5-fold emission enhancement and considerable piezochromism from green to red in a mild pressure interval of 1 atm to 2.5 GPa. The substantial distortion of both individual halide octahedron and the Pb-I-Pb angles between two halide octahedra under high pressure indeed determines the pressure-tuning localized excitons behavior. Upon higher pressure, photocurrent enhancement is also observed, which is attributed to the promoted electronic connectivity in (ACA)(MA)PbI4. The anisotropic compaction reduces the distance between neighboring organic molecules and {PbI6} octahedra, leading to the enhancement of hydrogen bonding interactions. This work not only offers a deep understanding of the structure-optical relationships of ACI-type perovskites, but also presents insights into breaking the limits of luminescent efficiency by pressure-suppressed nonradiative recombination.
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The abuse of kanamycin (KAN) poses an increasing threat to human health by contaminating agricultural and animal husbandry products, drinking water, and more. Therefore, the sensitive detection of trace KAN residues in real samples is crucial for monitoring agricultural pollution, ensuring food safety, and diagnosing diseases. However, traditional assay techniques for KAN rely on bulky instruments and complicated operations with unsatisfactory detection limits. Herein, we developed a novel label-free aptasensor to achieve ultrasensitive detection of KAN by constructing mesoporous DNA-cobalt@carbon nanofibers (DNA-Co@C-NFs) as the recognizer. Leveraging the extended π-conjugation structure, prominent surface area, and abundant pores, the Co@C-NFs can effectively load aptamer strands via π-π stacking interactions, serving as KAN capturer and reporter. Due to the change in DNA configuration upon binding KAN, this aptasensor presented an ultralow detection limit and ultra-wide linear range, along with favorable precision and selectivity. Using real tap water, milk, and human serum samples, the aptasensor accurately reported trace KAN levels. As a result, this convenient and rapid autosensing technique holds promise for onsite testing of other antibiotic residues in agriculture, food safety, and clinical diagnosis.
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Protein structure prediction is important for understanding their function and behavior. This review study presents a comprehensive review of the computational models used in predicting protein structure. It covers the progression from established protein modeling to state-of-the-art artificial intelligence (AI) frameworks. The paper will start with a brief introduction to protein structures, protein modeling, and AI. The section on established protein modeling will discuss homology modeling, ab initio modeling, and threading. The next section is deep learning-based models. It introduces some state-of-the-art AI models, such as AlphaFold (AlphaFold, AlphaFold2, AlphaFold3), RoseTTAFold, ProteinBERT, etc. This section also discusses how AI techniques have been integrated into established frameworks like Swiss-Model, Rosetta, and I-TASSER. The model performance is compared using the rankings of CASP14 (Critical Assessment of Structure Prediction) and CASP15. CASP16 is ongoing, and its results are not included in this review. Continuous Automated Model EvaluatiOn (CAMEO) complements the biennial CASP experiment. Template modeling score (TM-score), global distance test total score (GDT_TS), and Local Distance Difference Test (lDDT) score are discussed too. This paper then acknowledges the ongoing difficulties in predicting protein structure and emphasizes the necessity of additional searches like dynamic protein behavior, conformational changes, and protein-protein interactions. In the application section, this paper introduces some applications in various fields like drug design, industry, education, and novel protein development. In summary, this paper provides a comprehensive overview of the latest advancements in established protein modeling and deep learning-based models for protein structure predictions. It emphasizes the significant advancements achieved by AI and identifies potential areas for further investigation.
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Aprendizado Profundo , Modelos Moleculares , Conformação Proteica , Proteínas , Proteínas/química , Inteligência Artificial , Biologia Computacional/métodosRESUMO
ABSTRACTDrought presents a major challenge to the management of rocky desertification and ecological restoration in the delicate karst ecosystems of Guangxi. In this study, the normalized difference vegetation index (NDVI), fractional vegetation cover (FVC) and net primary productivity (NPP) were selected as vegetation remote sensing parameters, and the spatial response characteristics of different types of vegetation in karst areas of Guangxi Province to light, moderate, severe and extreme drought were analyzed to provide scientific basis for the evaluation of the impact of drought on vegetation in karst areas. The results are as follows: (1) NDVI, FVC and NPP showed a fluctuating increasing trend from 2000 to 2022, and the increasing rates were 0.058, 6.90%, and 43.3gC.m-2 per decade respectively. During this period, the number of light, moderate and severe drought days showed a decreasing trend, but the number of extreme drought days tended to increase. (2) The negative correlation of NDVI, FVC and NPP and drought increased from moderate to extreme drought, and from light to extreme drought, the negative correlation between NDVI and FVC and drought decreased, while that of NPP increased. (3) Light and moderate droughts had obvious negative impact on Chinese fir and broad-leaved forest, whereas severe and extreme droughts had obvious negative effect on eucalyptus and bamboo forest.
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In late 2019, the emergence of a novel coronavirus led to its identification as SARS-CoV-2, precipitating the onset of the COVID-19 pandemic. Many experimental and computational studies were performed on SARS-CoV-2 to understand its behavior and patterns. In this research, Molecular Dynamic (MD) simulation is utilized to compare the behaviors of SARS-CoV-2 and its Variants of Concern (VOC)-Alpha, Beta, Gamma, Delta, and Omicron-with the hACE2 protein. Protein structures from the Protein Data Bank (PDB) were aligned and trimmed for consistency using Chimera, focusing on the receptor-binding domain (RBD) responsible for ACE2 interaction. MD simulations were performed using Visual Molecular Dynamics (VMD) and Nanoscale Molecular Dynamics (NAMD2), and salt bridges and hydrogen bond data were extracted from the results of these simulations. The data extracted from the last 5 ns of the 10 ns simulations were visualized, providing insights into the comparative stability of each variant's interaction with ACE2. Moreover, electrostatics and hydrophobic protein surfaces were calculated, visualized, and analyzed. Our comprehensive computational results are helpful for drug discovery and future vaccine designs as they provide information regarding the vital amino acids in protein-protein interactions (PPIs). Our analysis reveals that the Original and Omicron variants are the two most structurally similar proteins. The Gamma variant forms the strongest interaction with hACE2 through hydrogen bonds, while Alpha and Delta form the most stable salt bridges; the Omicron is dominated by positive potential in the binding site, which makes it easy to attract the hACE2 receptor; meanwhile, the Original, Beta, Delta, and Omicron variants show varying levels of interaction stability through both hydrogen bonds and salt bridges, indicating that targeted therapeutic agents can disrupt these critical interactions to prevent SARS-CoV-2 infection.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Humanos , COVID-19/virologia , COVID-19/metabolismo , Ligação de Hidrogênio , Sítios de LigaçãoRESUMO
The Qilongtian capsule (QLT) is a Chinese patent medicine that has been approved for the treatment of chronic obstructive pulmonary disease (COPD). However, the precise pharmacodynamic material basis and molecular mechanism have not been well illustrated. In this study, we identified the effect of QLT on COPD through a cigarette smoke extract (CSE)/lipopolysaccharide (LPS) induced COPD mice model. The absorption of blood components in QLT were identified using ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to predict the potential targets and therapeutic mechanisms of QLT, which were further validated using in vivo experiments and molecular docking. Pharmacodynamic studies revealed that QLT could ameliorate pulmonary function and pulmonary pathology, reduce collagen fiber accumulation, and attenuate inflammatory responses in mice with CSE/LPS induced COPD. A total of 21 components of QLT absorbed in the blood were detected. Network pharmacology analysis indicated that TNF, IL-6, EGFR, and AKT1 may be the core targets, mainly involving the MAPK signaling pathway. Besides, Sachaloside II, Ginsenoside Rh1, Ginsenoside F1, Rosiridin, and Ginsenoside Rf were the key compounds. Molecular docking results showed that the key components could spontaneously bind to EGFR and MAPK to form a relatively stable conformation. In vivo experiments revealed that QLT could suppress the activation of the EGFR/MAPK signaling pathway, thereby improving lung injury in mice with COPD. Overall, these findings provide evidence for the treatment of COPD with QLT.
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Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.
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BACKGROUND: Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis. METHODS: The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD). RESULTS: The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation. CONCLUSIONS: The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers.
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Galinhas , Coccidiose , Coccidiostáticos , Eimeria tenella , Eucalyptus , Eugenol , Doenças das Aves Domésticas , Animais , Galinhas/parasitologia , Eimeria tenella/efeitos dos fármacos , Coccidiose/tratamento farmacológico , Coccidiose/veterinária , Coccidiose/parasitologia , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/parasitologia , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Coccidiostáticos/administração & dosagem , Eugenol/farmacologia , Eugenol/administração & dosagem , Eucalyptus/química , Produtos Biológicos/farmacologia , Produtos Biológicos/administração & dosagem , Oocistos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/administração & dosagemRESUMO
BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Adulto , Estudos Transversais , Idoso , Fatores de Risco , Inquéritos e Questionários , Doença AgudaRESUMO
OBJECTIVE: To study the molecular basis for a proband with A subtype B of the ABO blood group and explore the influence of amino acid variant on the activity of glycosyltransferase (GT). METHODS: A proband who had presented at the First Affiliated Hospital of Zhengzhou University on July 2, 2020 was selected as the study subject. Serological identification of the ABO blood groups of the proband and her family members were performed by gel card and test tube methods. The ABO gene of the proband was identified by PCR-sequence specific primers (PCR-SSP) and DNA sequencing. A 3D molecular homologous model was constructed to predict the impact of the variant on the stability of α-(1â3)-D-N-acetylgalactosamine transferase (GTA). RESULTS: The red blood cells of the proband, her mother and two younger brothers showed weak agglutination with anti-A and strong agglutination with anti-B. The sera showed 1~2+ agglutination with Ac and no agglutination with Bc. Based on the serological characteristics, the proband was identified as AwB subtype. Pedigree analysis suggested that the variant was inherited from her mother. The blood group of the proband was identified as A223B type by PCR-SSP. ABO gene sequencing analysis showed that the proband has harbored heterozygous variants of c.297A>G, c.467C>T, c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C, c.930G>A and c.1055insA. Based on the results of clone sequencing, it was speculated that the genotype was ABO*A223/ABO*B.01. There were c.467C>T and c.1055insA variants compared with ABO*A1.01, and c.1055insA variant compared with ABO*A1.02. Homologous modeling showed that the C-terminal of A223 GT was significantly prolonged, and the local amino acids and hydrogen bond network have changed. CONCLUSION: Above results revealed the molecular genetics mechanism of A223B subtype. The c.1055insA variant carried by the proband may affect the enzymatic activity of GTA and ultimately lead to weakening of A antigen.
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Sistema ABO de Grupos Sanguíneos , Linhagem , Humanos , Sistema ABO de Grupos Sanguíneos/genética , Feminino , Masculino , Adulto , N-Acetilgalactosaminiltransferases/genética , Genótipo , Tipagem e Reações Cruzadas SanguíneasRESUMO
Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.
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Anticorpos Antivirais , Formação de Anticorpos , Linfócitos B , Vacinas contra COVID-19 , COVID-19 , Centro Germinativo , Imunização Secundária , SARS-CoV-2 , Células T Auxiliares Foliculares , Animais , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Linfócitos B/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Camundongos , COVID-19/imunologia , COVID-19/prevenção & controle , Células T Auxiliares Foliculares/imunologia , Centro Germinativo/imunologia , Formação de Anticorpos/imunologia , Feminino , Hipermutação Somática de Imunoglobulina , Vacinação , Camundongos Endogâmicos BALB C , Humanos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Corona virus disease 2019(COVID-19) is one of the most serious respiratory pandemic diseases threatening human health for centuries. Alopecia areata (AA) is a sudden patchy hair loss, an autoimmune disease, which seriously affects the image and mental health of patients. Evidence shows that the risk of autoimmune diseases significantly increases after COVID-19, and is positively correlated with the severity, with a significant increase in the risk of alopecia in those over 40 years old. The relationship between COVID-19 and AA has become a hot topic of current research. Strengthening the research on the correlation between COVID-19 and AA can help to identify and protect susceptible populations at an early stage. This article reviews the research progress on the epidemiological background of COVID-19 and AA, the situation and possible mechanisms of AA induced by COVID-19 or COVID-19 vaccination, and potential treatment methods.
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Alopecia em Áreas , COVID-19 , SARS-CoV-2 , Alopecia em Áreas/epidemiologia , Alopecia em Áreas/imunologia , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologiaRESUMO
The ionizing radiation (IR) represents a formidable challenge as an environmental factor to mitochondria, leading to disrupt cellular energy metabolism and posing health risks. Although the deleterious impacts of IR on mitochondrial function are recognized, the specific molecular targets remain incompletely elucidated. In this study, HeLa cells subjected to γ-rays exhibited concomitant oxidative stress, mitochondrial structural alterations, and diminished ATP production capacity. The γ-rays induced a dose-dependent induction of mitochondrial fission, simultaneously manifested by an elevated S616/S637 phosphorylation ratio of the dynamin-related protein 1 (DRP1) and a reduction in the expression of the mitochondrial fusion protein mitofusin 2 (MFN2). Knockdown of DRP1 effectively mitigated γ-rays-induced mitochondrial network damage, implying that DRP1 phosphorylation may act as an effector of radiation-induced mitochondrial damage. The mitochondrial outer membrane protein voltage-dependent anion channel 1 (VDAC1) was identified as a crucial player in IR-induced mitochondrial damage. The VDAC1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), counteracts the excessive mitochondrial fission induced by γ-rays, consequently rebalancing the glycolytic and oxidative phosphorylation equilibrium. This metabolic shift was uncovered to enhance glycolytic capacity, thus fortifying cellular resilience and elevating the radiosensitivity of cancer cells. These findings elucidate the intricate regulatory mechanisms governing mitochondrial morphology under radiation response. It is anticipated that the development of targeted drugs directed against VDAC1 may hold promise in augmenting the sensitivity of tumor cells to radiotherapy and chemotherapy.