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The rapid progress of machine learning (ML) in predicting molecular properties enables high-precision predictions being routinely achieved. However, many ML models, such as conventional molecular graph, cannot differentiate stereoisomers of certain types, particularly conformational and chiral ones that share the same bonding connectivity but differ in spatial arrangement. Here, we designed a hybrid molecular graph network, Chemical Feature Fusion Network (CFFN), to address the issue by integrating planar and stereo information of molecules in an interweaved fashion. The three-dimensional (3D, i.e., stereo) modality guarantees precision and completeness by providing unabridged information, while the two-dimensional (2D, i.e., planar) modality brings in chemical intuitions as prior knowledge for guidance. The zipper-like arrangement of 2D and 3D information processing promotes cooperativity between them, and their synergy is the key to our model's success. Experiments on various molecules or conformational datasets including a special newly created chiral molecule dataset comprised of various configurations and conformations demonstrate the superior performance of CFFN. The advantage of CFFN is even more significant in datasets made of small samples. Ablation experiments confirm that fusing 2D and 3D molecular graphs as unambiguous molecular descriptors can not only effectively distinguish molecules and their conformations, but also achieve more accurate and robust prediction of quantum chemical properties.
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Aprendizado de Máquina , Estereoisomerismo , Conformação MolecularRESUMO
Cardiomyocytes undergo a variety of cell death events during myocardial ischemiaâreperfusion injury (MIRI). Understanding the causes of cardiomyocyte mortality is critical for the prevention and treatment of MIRI. Among the various types of cell death, autosis is a recently identified type of autophagic cell death with distinct morphological and chemical characteristics. Autosis can be attenuated by autophagy inhibitors but not reversed by apoptosis or necrosis inhibitors. In recent years, it has been shown that during the late phase of reperfusion, autosis is activated, which exacerbates myocardial injury. This article describes the characteristics of autosis, autophagic cell death, and the relationship between autophagic cell death and autosis; reviews the mechanism of autosis in MIRI; and discusses its clinical significance.
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OBJECTIVE: Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs). METHODS: FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits. RESULTS: Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia. CONCLUSIONS: NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.
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Artrite Reumatoide , Ferroptose , Sinoviócitos , Humanos , Lipopolissacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Interleucina-8/metabolismo , Artrite Reumatoide/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Hipóxia/metabolismo , Fatores de Transcrição/metabolismo , RNA Interferente Pequeno/genética , Fibroblastos/metabolismo , Ferro/metabolismo , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismoRESUMO
Adipose tissue in the obese state can lead to low-grade chronic inflammation while inducing or exacerbating obesity-related metabolic diseases and impairing overall health.T cells, which are essential immune cells similar to macrophages, are widely distributed in adipose tissue and perform their immunomodulatory function; they also cross-talk with other cells in the vascular stromal fraction. Based on a large number of studies, it has been found that N6 methyl adenine (m6A) is one of the most representative of epigenetic modifications, which affects the crosstalk between T cells, as well as other immune cells, in several ways and plays an important role in the development of adipose tissue inflammation and related metabolic diseases. In this review, we first provide an overview of the widespread presence of T cells in adipose tissue and summarize the key role of T cells in adipose tissue inflammation. Next, we explored the effects of m6A modifications on T cells in adipose tissue from the perspective of adipose tissue inflammation. Finally, we discuss the impact of m6a-regulated crosstalk between T cells and immune cells on the prospects for improving adipose tissue inflammation research, providing additional new ideas for the treatment of obesity.
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Tecido Adiposo , Inflamação , Linfócitos T , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/imunologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/imunologia , Linfócitos T/metabolismo , Linfócitos T/imunologia , Animais , Obesidade/metabolismo , Obesidade/patologia , Obesidade/imunologia , Epigênese Genética , Adenosina/metabolismoRESUMO
PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1-L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (Fz) of THOR-AV and THUMS changed in the similar trend. The maximum Fz ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (My) and the time when the maximum My occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of My measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION: The Fz of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on Fz. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map My directly because they are very different in ATD and HBM. The My of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
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Bronchopulmonary dysplasia (BPD) is a pulmonary disease commonly observed in premature infants and it is reported that oxidative stress is a critical induction factor in BPD and is considered as a promising target for treating BPD. Nesfatin-1 is a brain-gut peptide with inhibitory effects on food intake, which is recently evidenced to show suppressive effect on oxidative stress. The present study aims to explore the therapeutic effect and mechanism of Nesfatin-1 in BPD mice. AECIIs were extracted from newborn rats and exposed to hyperoxia for 24 h, followed by treatment with 5 and 10 nM Nesfatin-1. Declined cell viability, increased apoptotic rate, upregulated Bax, downregulated Bcl-2, increased release of ROS and MDA, and suppressed SOD activity were observed in hyperoxia-treated AECIIs, which were extremely reversed by Nesfatin-1. Newborn rats were exposed to hyperoxia, followed by treated with 10 µg/kg Nesfatin-1 and 20 µg/kg Nesfatin-1. Severe pathological changes, elevated MDA level, and declined SOD activity were observed in lung tissues of BPD mice, which were rescued by Nesfatin-1. Furthermore, the protective effect of Nesfatin-1 on hyperoxia-challenged AECIIs was abolished by silencing SIRT1. Collectively, Nesfatin-1 alleviated hyperoxia-induced lung injury in newborn mice by inhibiting oxidative stress through regulating SIRT1/PGC-1α pathway.
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Displasia Broncopulmonar , Hiperóxia , Nucleobindinas , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/terapia , Hiperóxia/complicações , Animais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Nucleobindinas/farmacologia , Nucleobindinas/uso terapêutico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Superóxido Dismutase/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Malondialdeído/metabolismo , Ratos Sprague-Dawley , Masculino , FemininoRESUMO
Sirtuins are a family of NAD+ -dependent deacetylases that regulate some important biological processes, including lipid metabolism and autophagy, through their deacetylase function. Autophagy is a new discovery in the field of lipid metabolism, which may provide a new idea for the regulation of lipid metabolism. There are many tandem parts in the regulation process of lipid metabolism and autophagy of sirtuins protein family. This paper summarized these tandem parts and proposed the possibility of sirtuins regulating lipid autophagy, as well as the interaction and synergy between sirtuins protein family. Currently, some natural drugs have been reported to affect metabolism by regulating sirtuins, some of which regulate autophagy by targeting sirtuins.
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Metabolismo dos Lipídeos , Sirtuínas , Sirtuínas/metabolismo , Proteínas/metabolismo , AutofagiaRESUMO
Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract that significantly impacts the health of patients and lacks promising methods of diagnosis. Tumor-associated macrophages (TAMs) are involved in CRC progression, and their function is regulated by long non-coding RNAs (lncRNAs). The lncRNA NBR2 was recently reported as an oncogene, whose function in CRC remains uncertain. The present study aimed to investigate the biological function of lncRNA NBR2 in the progression of CRC and its underlying molecular mechanisms. Ten pairs of clinical CRC and para-carcinoma tissues were collected to determine the expression levels of lncRNA NBR2 and miR-19a, and the polarization state of TAMs. Quantitative reverse transcriptase-polymerase chain reaction was used to evaluate the expression of miR-19a, and western blotting was used to determine the expression levels of tumor necrosis factor-α, human leukocyte antigen-DR, arginase-1, CD163, CD206, interleukin-4, AMP-activated protein kinase (AMPK), p-AMPK, hypoxia-inducible factor-1α (HIF-1α), protein kinase B (AKT), p-AKT, mechanistic target of rapamycin (mTOR), and p-mTOR in TAMs. The proliferative ability of HCT-116 cells was detected using the CCK8 assay, and the migratory ability of HCT-116 cells was evaluated using the Transwell assay. The interaction between lncRNA NBR2 and miR-19a was determined using the luciferase assay. The lncRNA NBR2 was downregulated and miR-19a was highly expressed in CRC cells, accompanied by a high M2 polarization. Downregulated miR-19a promoted M1 polarization, activated AMPK, suppressed HIF-1α and AKT/mTOR signaling pathways, and promoted antitumor properties in NBR2-overexpressed TAMs, which were all reversed by the introduction of the miR-19a mimic. LncRNA NBR2 was verified to target miR-19a in macrophages according to the results of the luciferase assay. Collectively, lncRNA NBR2 may suppress the progression of CRC by downregulating miR-19a to regulate M2 macrophage polarization.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Luciferases/metabolismo , Macrófagos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Little research has been conducted on the spatio-temporal relationship between the severe cases and the enteroviruses infections of hand, foot and mouth disease (HFMD). This study aimed to investigate epidemic features and spatial clusters of HFMD incidence rates and assess the relationship between Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) and severe cases of HMFD in Gansu province, China. METHODS: Weekly county-specific data on HFMD between 1st January and 31st December 2018 were collected from the China Infectious Disease Information System (CIDIS), including enterovirus type (EV71 and CoxA16), severe and non-severe cases in Gansu province, China. Temporal risk [frequency index (α), duration index (ß) and intensity index (γ)] and spatial cluster analysis were used to assess epidemic features and identify high-risk areas for HFMD. Time-series cross-correlation function and regression model were used to explore the relationship between the ratios of two types of viruses (i.e. EV71/Cox16) (EC) and severe cases index (i.e. severe cases/non-severe cases) (SI) of HFMD. RESULTS: Some counties in Dingxi City, Gansu were identified as a hot spot for the temporal risk indices. Time-series cross-correlation analysis showed that SI was significantly associated with EC (r = 0.417, P < 0.05) over a 4-week time lag. The regression analysis showed that SI was positively associated with EC (ß = 0.04, 95% confidence interval (CI) 0.02-0.06). CONCLUSION: The spatial patterns of HFMD incidence were associated with enteroviruses in Gansu. The research suggested that the EC could be considered a potential early warning sign for predicting severe cases of HFMD in Gansu province.
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Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , China/epidemiologia , Vírus de DNA , Doença de Mão, Pé e Boca/epidemiologia , HumanosRESUMO
In recent decades, nanomaterial-based artificial enzymes called nanozymes have received more and more attention and have been applied in biological, chemical, medical, and other fields. In this work, bimetallic FeMn@C was synthesized by calcination from the Prussian blue analogue. The synthesized bimetallic FeMn@C exhibits efficient peroxidase-like activity. The effect of Mn doping amount, catalytic kinetics, and mechanism of FeMn@C nanozyme was further studied in detail. The results show that the peroxidase-like activity of bimetallic FeMn@C is nearly 16 times higher than that of single-metal Fe@C. The peroxidase-like activity of FeMn@C originates from its production of radicals. Compared with natural enzymes, FeMn@C nanozyme has a better affinity for the substrates. Besides, FeMn@C nanozyme has better stability than natural enzymes. Because of its strong magnetism, FeMn@C nanozyme can be recycled easily and exhibits excellent recycling performance. Based on the good affinity of FeMn@C for H2O2, a rapid and selective colorimetric assay for glucose detection is constructed, with a wide linear range of 0.01-0.75 mM and low detection limit of 4.28 µM. This sensor has been successfully applied to the determination of glucose in fruit juice, showing good selectivity and accuracy. The synthesis of bimetallic FeMn@C provides a feasible way to design nanozymes with excellent catalytic activity, high stability, and easy separation.
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Colorimetria , Peróxido de Hidrogênio , Colorimetria/métodos , Ferrocianetos , Glucose , PeroxidasesRESUMO
The authors proposed a novel template-free strategy, urease-mediated interfacial growth of NH4 Ga(OH)2 CO3 nanotubes at 20-50 °C, to fabricate the porous Ga2 O3 nanotubes. The subtlety of the proposed strategy is all the products from urea enzymolysis are utilized in formation of NH4 Ga(OH)2 CO3 precipitates, and the key for interfacial growth of NH4 Ga(OH)2 CO3 nanotubes is the dynamic match between the rate of CO2 bubble fusion and NH4 Ga(OH)2 CO3 precipitation. The proposed strategy works well for the doped porous Ga2 O3 nanotubes. As a proof-of-concept, the porous ß-Ga2 O3 and ß-Ga2 O3 :Cr0.001 nanotubes are used as photocatalysts or co-catalysts with Pt, for H2 evolution from water splitting. The H2 evolution rate of porous ß-Ga2 O3 nanotubes reach 39.3 mmol g-1 h-1 with solar-to-hydrogen (STH) conversion efficiency of 2.11% (Hg lamp) or 498 µmol g-1 h-1 with STH of 0.03% (Xe lamp) respectively, both about 3 times of ß-Ga2 O3 nanoparticles synthesized at pH 9.0 without urease. The Cr-doping enhances the in-the-dark H2 evolution rate pre-lighted by Hg lamp, and Pt co-catalysis further elevates the H2 evolution rate, for instance, the H2 evolution rate of Pt-loaded ß-Ga2 O3 :Cr0.001 nanotubes reaches 54.7 mmol g-1 h-1 with STH of 2.94% under continuous lighting of Hg lamp and 1062 µmol g-1 h-1 in-the-dark.
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Carbonatos , Gálio , Hidrogênio , Nanotubos , Urease , Catálise , PorosidadeRESUMO
The aggregation of the amyloid-ß (Aß) peptide is linked to the pathogenesis of Alzheimer's disease (AD). In particular, some point mutations within Aß are associated with early-onset familial Alzheimer's disease. Here we set out to explore how the physical properties of the altered side chains, including their sizes and charges, affect the molecular mechanisms of aggregation. We focus on Aß42 with familial mutations-A21G (Flemish), E22K (Italian), E22G (Arctic), E22Q (Dutch), and D23N (Iowa)-which lead to similar or identical pathology with sporadic AD or severe cerebral amyloid angiopathy. Through global kinetic analysis, we find that for the E22K, E22G, E22Q, and D23N mutations, the acceleration of the overall aggregation originates primarily from the modulation of the nucleation processes, in particular secondary nucleation on the surface of existing fibrils, whereas the elongation process is not significantly affected. Remarkably, the D23 position appears to be responsible for most of the charge effects during nucleation, while the size of the side chain at the E22 position plays a more significant role than its charge. Thus, we have developed a kinetic approach to determine the nature and the magnitude of the contribution of specific residues to the rate of individual steps of the aggregation reaction, through targeted mutations and variations in ionic strength. This strategy can help rationalize the effect of some disease-related mutations as well as yield insights into the mechanism of aggregation and the transition states of the wild-type protein.
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Doença de Alzheimer/genética , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/genética , Mutação de Sentido Incorreto , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Agregação Patológica de Proteínas/genética , Doença de Alzheimer/metabolismo , Substituição de Aminoácidos , Peptídeos beta-Amiloides/metabolismo , Humanos , Fragmentos de Peptídeos/metabolismo , Agregação Patológica de Proteínas/metabolismoRESUMO
Serious scale variation is a key challenge in pedestrian detection. Most works typically employ a feature pyramid network to detect objects at diverse scales. Such a method suffers from information loss during channel unification. Inadequate sampling of the backbone network also affects the power of pyramidal features. Moreover, an arbitrary RoI (region of interest) allocation scheme of these detectors incurs coarse RoI representation, which becomes worse under the dilemma of small pedestrian relative scale (PRS). In this paper, we propose a novel scale-sensitive feature reassembly network (SSNet) for pedestrian detection in road scenes. Specifically, a multi-parallel branch sampling module is devised with flexible receptive fields and an adjustable anchor stride to improve the sensitivity to pedestrians imaged at multiple scales. Meanwhile, a context enhancement fusion module is also proposed to alleviate information loss by injecting various spatial context information into the original features. For more accurate prediction, an adaptive reassembly strategy is designed to obtain recognizable RoI features in the proposal refinement stage. Extensive experiments are conducted on CityPersons and Caltech datasets to demonstrate the effectiveness of our method. The detection results show that our SSNet surpasses the baseline method significantly by integrating lightweight modules and achieves competitive performance with other methods without bells and whistles.
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Pedestres , HumanosRESUMO
Our work used cecal ligation and puncture (CLP) mice model and 16S rDNA sequencing to explore whether the therapeutic mechanism of Sini Decoction (SND) on sepsis was related to the intestinal flora currently of concern. Twenty-four hours after surgery, tissues and serum from three groups (Control, CLP and CLP + SND) were collected for further analysis and colon contents were isolated for 16S rDNA analysis. Mortality, histological examination and inflammatory cytokines levels confirmed that the sepsis model was induced successfully and resulted in serious pathological damage, while all of these could be reversed by SND. In intestinal flora analysis, the microbial richness and abundance were recovered after SND treatment. Furthermore, at the phylum level, the abundance of Proteobacteria showed drastic increase after CLP. Similarly, CLP surgery significantly disrupted the balance of intestinal flora, with a huge increase of Escherichia-Shigella, a Gram-negative genus that might release lipopolysaccharide (LPS) and other genera. And these shifts could be defused by SND, indicating its function of regulating gut microbiota. This study demonstrates that SND could ameliorate the symptoms and pathology associated with sepsis in CLP model via modulating the flora in intestinal tract, which enriches a possible mechanism of SND's therapeutic effect.
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Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Lesão Pulmonar/tratamento farmacológico , Sepse/tratamento farmacológico , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/efeitos dos fármacos , Ceco/microbiologia , Modelos Animais de Doenças , Humanos , Lesão Pulmonar/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sepse/microbiologiaRESUMO
BACKGROUNDS: Seasonal influenza remains epidemic globally with a substantial health burden. Understanding the transmission patterns and epidemic features of influenza may facilitate the improvement of preventive and control measures. This study aims to assess the epidemic features of influenza among different climate zones and identify high-risk zones across Gansu province, China. METHODS: We collected weekly influenza cases at county-level between 1st January 2012 and 31st December 2016, as well as climate zones classification shapefile data from Köppen-Geiger climate map. We compared the epidemic features (Frequency index (α), Duration index (ß) and Intensity index (γ)) of influenza among different climate zones. Spatial cluster analysis was used to examine the high-risk areas of transmission of influenza. RESULTS: The distribution of cases existed significant differences among eight climate zones (F-test: 267.02, p < 0.05). The highest mean weekly incidence rate (per 100,000 population) was 0.59 in snow climate with dry winter and warm summer (Dwb). The primary (relative risk (RR): 3.61, p < 0.001) and secondary (RR: 2.45, p < 0.001) clusters were located in Dwb. The highest values of α, ß and γ were 1.00, 261 and 154.38 in Dwb. The hot spots (high-high clusters) of the epidemic indices were detected in Dwb. CONCLUSIONS: This study found the variability of epidemic features of influenza among eight climate zones. We highlight that Dwb was the high-risk zone where influenza clustered with the highest incidence rate and epidemic temporal indices. This provide further insight into potential improvement of preventive measures by climate zones to minimize the impact of epidemics.
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Epidemias , Influenza Humana , China/epidemiologia , Clima , Humanos , Influenza Humana/epidemiologia , Estações do AnoRESUMO
BACKGROUND: The COVID-19 pandemic has recently spread dramatically worldwide, raising considerable concerns and resulting in detrimental effects on the psychological health of people who are vulnerable to the disease. Therefore, assessment of depression in members of the general public and their psychological and behavioral responses is essential for the maintenance of health. OBJECTIVE: This study aimed to assess the prevalence of depression and the associated factors among the general public during the early stages of the COVID-19 pandemic in China. METHODS: A cross-sectional survey with convenience sampling was conducted from February 11 to 16, 2020, in the early stages of the COVID-19 outbreak in China. A self-administrated smartphone questionnaire based on the Patient Health Questionnaire-9 (PHQ-9) and psychological and behavioral responses was distributed to the general public. Hierarchical multiple regression analysis and multivariate logistic regression analysis were conducted to explore the associated factors of depression.aA cross-sectional survey with convenience sampling was conducted from February 11 to 16, 2020, in the early stages of the COVID-19 outbreak in China. A self-administrated smartphone questionnaire based on the Patient Health Questionnaire-9 (PHQ-9) and psychological and behavioral responses was distributed to the general public. Hierarchical multiple regression analysis and multivariate logistic regression analysis were conducted to explore the associated factors of depression. RESULTS: The prevalence of depression (PHQ-9 score ≥10) among the general public during the COVID-19 pandemic was 182/1342 (13.6%). Regression analysis indicated that feeling stressed, feeling helpless, persistently being worried even with support, never feeling clean after disinfecting, scrubbing hands and items repeatedly, hoarding food, medicine, or daily supplies, and being distracted from work or study were positively associated with depression, while social support and being calm were negatively associated with depression. CONCLUSIONS: The general public suffered from high levels of depression during the early stages of the COVID-19 pandemic. Thus, COVID-19-related mood management and social support should be provided to attenuate depression in the general public.
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Ansiedade/epidemiologia , Infecções por Coronavirus/epidemiologia , Depressão/epidemiologia , Inquéritos Epidemiológicos , Saúde Mental/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Ansiedade/psicologia , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/psicologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Pneumonia Viral/psicologia , Prevalência , SARS-CoV-2 , Autorrelato , SmartphoneRESUMO
A novel Gram-stain negative, strictly aerobic, rod-shaped motile bacterium with a single flagellum, designated strain DASS28T, was isolated from surface sediment of Bohai Sea in China. Growth occurred in the presence of 1.0-4.0% NaCl (w/v, optimum 2.0%), at 10-37 °C (optimum 20 °C) on the Marine agar 2216E and pH 6.0-10.0 (optimum pH 8.0). The major fatty acids (> 10% of total fatty acids) were summed feature 3 (C16:1ω7c and/or iso-C15:0 2-OH), C16:0 and C18:1ω7c. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and two unidentified polar lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The genomic DNA G + C content calculated from the genome sequence of strain DASS28T was 48.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain DASS28T belongs to the genus Corallincola and shows high 16S rRNA gene sequence similarity of 96.7% to Corallincola platygyrae JLT 2006T (= JCM18796T = CGMCC 1.10992T). On the basis of the polyphasic evidence, strain DASS28T is considered to represent a novel species in the genus Corallincola, for which the name Corallincola luteus sp. nov. is proposed. The type strain is DASS28T (= KCTC 52376T = MCCC 1K03208T).
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Organismos Aquáticos/classificação , Organismos Aquáticos/isolamento & purificação , Gammaproteobacteria/classificação , Gammaproteobacteria/isolamento & purificação , Sedimentos Geológicos/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/microbiologiaRESUMO
The human molecular chaperone DNAJB6, an oligomeric protein with a conserved S/T-rich region, is an efficient suppressor of amyloid fibril formation by highly aggregation-prone peptides such as the Aß and polyQ peptides associated with Alzheimer's and Huntington's disease, respectively. We previously showed that DNAJB6 can inhibit the processes through which amyloid fibrils are formed via strong interactions with aggregated forms of Aß42 that become sequestered. Here we report that the concentration-dependent capability of DNAJB6 to suppress fibril formation in thioflavin T fluorescence assays decreases progressively with an increasing number of S/T substitutions, with an almost complete loss of suppression when 18 S/T residues are substituted. The kinetics of primary nucleation in particular are affected. No detectable changes in the structure are caused by the substitutions. Also, the level of binding of DNAJB6 to Aß42 decreases with the S/T substitutions, as determined by surface plasmon resonance and microscale thermophoresis. The aggregation process monitored using nuclear magnetic resonance spectroscopy showed that DNAJB6, in contrast to a mutational variant with 18 S/T residues substituted, can keep monomeric Aß42 soluble for an extended time. The inhibition of the primary nucleation is likely to depend on hydroxyl groups in side chains of the S/T residues, and hydrogen bonding with Aß42 is one plausible molecular mechanism, although other possibilities cannot be excluded. The loss of the ability to suppress fibril formation upon S/T to A substitution was previously observed also for polyQ peptides, suggesting that the S/T residues in the DNAJB6-like chaperones have a general ability to inhibit amyloid fibril formation by different aggregation-prone peptides.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Proteínas de Choque Térmico HSP40/química , Proteínas de Choque Térmico HSP40/metabolismo , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Amiloide/química , Peptídeos beta-Amiloides/química , Humanos , Ligação de Hidrogênio , Modelos Biológicos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismoRESUMO
BACKGROUND: To determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission. METHOD: Weekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways. RESULTS: GLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui. CONCLUSION: Average temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity's effect on HFMD showed a non-linear interacting relationship with average temperature.
Assuntos
Doença de Mão, Pé e Boca/epidemiologia , Criança , China/epidemiologia , Clima , Doença de Mão, Pé e Boca/etiologia , Humanos , Incidência , Modelos Lineares , Temperatura , Tempo (Meteorologia)RESUMO
A Gram-stain-negative, strictly aerobic, non-flagellated, non-gliding, catalase-positive, long-rod-shaped bacterium designated strain CSW06T, was isolated from surface seawater of the Bohai Sea. Optimal growth occurred in the presence of 4â% (w/v) NaCl, at pH 7 and at 28 °C. The predominant fatty acids (>10â% of total fatty acids) were iso-C15â:â1G, iso-C17â:â0 3-OH and summed feature 3 (iso-C15â:â0 2-OH and/or C16â:â1ω7c). The major polar lipids were phosphatidylethanolamine, two unidentified phospholipids and one unidentified aminolipid. The DNA G+C content of CSW06T was 50.3 mol%. The predominant isoprenoid quinone detected was menaquinone with six isoprene units (MK-6). On the basis of the results of polyphasic analyses, CSW06T was considered to represent a novel species of the genus Muricauda in the family Flavobacteriaceae, for which the name Muricauda lutea sp. nov. is proposed. The type strain is CSW06T (=CGMCC 1.15761T=JCM 31455T=KCTC 52375T=MCCC 1K03195T).