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OBJECTIVE: This study aimed to evaluate the burden of kidney dysfunction (KD), assess socioeconomic inequalities, and project trends in the future. METHODS: Data on deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were from Global Burden of Disease Study 2019. The Joinpoint regression model was utilized to analyze the temporal trend by the annual percentage change (APC). The slope index and concentration index were employed to evaluate cross-country disparities. The future trend was predicted using an age-period-cohort analysis. RESULTS: In the past three decades, the death numbers of KD increased from 1,571,720 to 3,161,552, DALYs from 42,090,331 to 76,486,945, YLDs from 5,003,267 to 11,282,484, and YLLs from 37,087,065 to 65,204,461, respectively. The age-standardized rate (ASR) of deaths, DALYs, and YLLs exhibited a declining trend. The ASR of YLDs increased until 2017, then decreased. The slope index and concentration index for DALYs increased from 248.1 to 351.9 and from 40.70 to 57.8. In the future, the ASR of deaths, DALYs, YLDs, and YLLs will remain stable, while their numbers will continue to rise, except for YLLs. CONCLUSIONS: The disease burden of KD remained serious. Tailored interventions should be developed based on national contexts.
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The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.
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Enzima de Conversão de Angiotensina 2 , Anticorpos Monoclonais , COVID-19 , Evasão da Resposta Imune , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/genética , COVID-19/imunologia , COVID-19/virologia , COVID-19/metabolismo , Sítios de Ligação , Modelos Moleculares , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , MutaçãoRESUMO
Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impact on meiosis, a special cell division essential for the delivery of genetic information across generations in eukaryotes, has not yet been elucidated. In this study, by performing cytogenetic studies, we reported that UV radiation does not damage meiotic chromosome integrity but attenuates centromere-mediated chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We showed that functional centromere-specific histone 3 (CENH3) is required for obligate crossover formation and plays a role in the protection of sister chromatid cohesion under UV stress. Moreover, we found that UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. We determined that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but possibly occurs via altered JASON function and downregulated Parallel Spindle1. This study provides evidence that UV radiation influences meiotic genome stability and gametophytic ploidy consistency in flowering plants.
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Despite extensive study, geochemical modeling often fails to accurately predict lead (Pb) immobilization in environmental samples. This study employs the Charge Distribution MUlti-SIte Complexation (CD-MUSIC) model, X-ray absorption fine structure (XAFS), and density functional theory (DFT) to investigate mechanisms of phosphate (PO4) induced Pb immobilization on metal (hydr)oxides. The results reveal that PO4 mainly enhances bidentate-adsorbed Pb on goethite via electrostatic synergy at low PO4 concentrations. At relatively low pH (below 5.5) and elevated PO4 concentrations, the formation of the monodentate-O-sharing Pb-PO4 ternary structure on goethite becomes important. Precipitation of hydropyromorphite (Pb5(PO4)3OH) occurs at high pH and high concentrations of Pb and PO4, with an optimized log Ksp value of -82.02. The adjustment of log Ksp compared to that in the bulk solution allows for quantification of the overall Pb-PO4 precipitation enhanced by goethite. The CD-MUSIC model parameters for both the bidentate Pb complex and the monodentate-O-sharing Pb-PO4 ternary complex were optimized. The modeling results and parameters are further validated and specified with XAFS analysis and DFT calculations. This study provides quantitative molecular-level insights into the contributions of electrostatic enhancement, ternary complexation, and precipitation to phosphate-induced Pb immobilization on oxides, which will be helpful in resolving controversies regarding Pb distribution in environmental samples.
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Chumbo , Fosfatos , Chumbo/química , Fosfatos/química , Compostos de Ferro/química , Minerais/química , Concentração de Íons de Hidrogênio , AdsorçãoRESUMO
OBJECTIVE: With this study, we aimed to estimate the disease burden attributable to child and maternal malnutrition (CMM) throughout the world between 1990 and 2019. METHODS: The number, age-standardized rate, population attributable fraction of deaths, disability-adjusted life-years, years of life lost, and years lived with disability associated with CMM were estimated using the Global Burden of Disease Study 2019 by age, sex, year, location, and sociodemographic index at the global level. The slope index of inequality and concentration index were employed to measure socioeconomic-related health inequalities across countries. RESULTS: The number (million) of global deaths, disability-adjusted life-years, and years of life lost related to CMM were 2.9, 294.8, and 250.5 in 2019, showing decreases of 60.8, 57.4, and 60.7% since 1990. However, the number of years lived with CMM-related disability increased from 36.0 in 1990 to 44.3 in 2019. Additionally, the age-standardized rates of these 4 indicators showed varying degrees of decline. The global burden of CMM-related conditions differed with age and sex. The burden was the heaviest in western sub-Saharan Africa, especially in Chad. In terms of diseases, neonatal disorders represented the most significant burden attributed to CMM. Additionally, the CMM burden was more concentrated in regions with low sociodemographic indices, shown by the slope index of inequality and concentration index. CONCLUSIONS: The findings of this study highlight the ongoing global burden of CMM, particularly in terms of years lived with disability. Population-wide actions targeting the effective treatment and relief of CMM may reduce the CMM-related disease burden.
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Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Humanos , Carga Global da Doença/tendências , Feminino , Pré-Escolar , Masculino , Criança , Lactente , Anos de Vida Ajustados por Deficiência/tendências , Desnutrição/epidemiologia , Saúde Global , Transtornos da Nutrição Infantil/epidemiologia , Recém-Nascido , Adolescente , Gravidez , Efeitos Psicossociais da DoençaRESUMO
The number of thoracic vertebrae (NTV) in pigs is an important economic trait that significantly influences pork production. While the Licha black pig is a well-known Chinese pig breed with multiple thoracic vertebrae, the genetic mechanism is still unknown. Here, we performed a selective signal analysis on the genome of Licha black pigs, comparing individuals with 15 NTV versus those with 16 NTV to better understand functional genes associated with NTV. A total of 2265 selection signal regions were detected across the genome, including 527 genes and 1073 QTL that overlapped with the selection signal regions. Functional enrichment analysis revealed that LRP5 and SP5 genes were involved in biological processes such as bone morphogenesis and Wnt protein binding. Furthermore, three genes, LRP8, DEF6, and SCUBE3, associated with osteoblast differentiation and bone formation, were located within or close to the QTL related to bone development and vertebrae number. These five genes were hypothesized to be potential candidates for regulating the NTV trait in Licha black pigs. Our findings revealed several candidate genes that play crucial roles in NTV regulation and provide a theoretical foundation to understand the genetic mechanism of the NTV trait in pig breeding.
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Locos de Características Quantitativas , Vértebras Torácicas , Animais , Suínos/genética , Cruzamento , Sus scrofa/genéticaRESUMO
Zinc is one of human essential metals. In this study, 101 kinds of daily food for residents, including vegetables, aquatic food, meat, fruits, rice and cereal products, pulse food, dairy products and eggs, were collected at various agricultural markets and supermarkets in Guangzhou city, China, and their zinc contents were determined. The results showed oyster is most abundant in zinc (703.5 ± 25.6 mg/kg), followed by high-zinc milk powder (58.63 ± 0.90 mg/kg), pulse food, mutton, beef and pig liver with zinc contents above 30 mg/kg. The zinc contents of rice and cereal products, milk powder, poultry, pork, some aquatic food and eggs are also relatively high (>10 mg/kg), while vegetables and fruits have zinc contents significantly below 10 mg/kg. The daily zinc intake per person was determined by considering the zinc content of various food types and the dietary habits of specific demographic groups, resulting in 12.3 mg/day for the normal person, 11.2 mg/day for low-income individual, 12.3 mg/day for middle-income individual, 13.3 mg/day for high-income individual, 10.2 mg/day for older individual, 12.9 mg/day for factory worker, 11.5 mg/day for college student, and 8.4 mg/day for kindergarten child. The reference values of zinc intake recommended by the Chinese Nutrition Society were used to evaluate the zinc intake of Guangzhou residents, showing that the residents' zinc intake is generally sufficient and not necessary to use zinc supplementation. Income, age and occupation could have posed influence on dietary intake of zinc.
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Doping in transition metal dichalcogenide (TMD) has received extensive attention for its prospect in the application of photoelectric devices. Currently researchers focus on the doping ability and doping distribution in monolayer TMD and have obtained a series of achievements. Bilayer TMD has more excellent properties compared with monolayer TMD. Moreover, bilayer TMD with different stacking structures presents varying performance due to the difference in interlayer coupling. Herein, this work focuses on doping ability of dopants in different bilayer stacking structures that has not been studied yet. Results of this work show that the doping ability of V atoms in bilayer AA' and AB stacked WS2 is different, and the doping concentration of V atoms in AB stacked WS2 is higher than in AA' stacked WS2. Moreover, dopants from top and bottom layer can be distinguished by scanning transmission electron microscopy (STEM) image. Density functional theory (DFT) calculation further confirms the doping rule. This study reveals the mechanism of the different doping ability caused by stacking structures in bilayer TMD and lays a foundation for further preparation of controllable-doping bilayer TMD materials.
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Patients with neurodegenerative diseases exhibit diminished basal forebrain (BF) volume compared to healthy individuals. However, it's uncertain whether this difference is consistent between sexes. It has been reported that BF volume moderately atrophies during aging, but the effect of sex on BF volume changes during the normal aging process remains unclear. In the cross-sectional study, we observed a significant reduction in BF volume in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to Healthy Controls (HCs), especially in the Ch4 subregion. Notably, significant differences in BF volume between MCI and HCs were observed solely in the female group. Additionally, we identified asymmetrical atrophy in the left and right Ch4 subregions in female patients with AD. In the longitudinal analysis, we found that aging seemed to have a minimal impact on BF volume in males. Our study highlights the importance of considering sex as a research variable in brain science.
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Chlorobenzene (CB) is a prevalent organic contaminant in water and soil environments. It presents high chemical stability and is resistant to both oxidation and reduction. In this study, we showed that CB was substantially removed by soluble Mn(III) produced during the reductive dissolution of colloidal MnO2 by naturally-occurring organic acids such as formate (FOR), oxalate (OX), and citrate (CIT). The removal rate was dependent on the physicochemical properties of organic acids. With strong electron-donating and coordination ability, OX and CIT promoted MnO2 dissolution and Mn(III) generation compared to FOR, but had adverse effects on the stability and reactivity of Mn(III). As a result, CB removal followed the order: MnO2/CIT > MnO2/FOR > MnO2/OX. Analysis of the transformation products showed that Mn(III) complexes acted as strong electrophiles, attacking the ortho/para carbons of the benzene ring and transforming CB to chlorophenols via an electrophilic substitution mechanism. The theoretical foundation of this proposed reaction mechanism was supplemented by quantum mechanical calculations. Together, the findings of this study provide new insights into the transformation of CB in natural environments and hold the potential to offer a novel strategy for the development of manganese oxide/ligand systems for CB elimination.
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Clorofenóis , Óxidos , Óxidos/química , Compostos de Manganês/química , Oxirredução , Água , Compostos OrgânicosRESUMO
In contaminated soil sites, the coexistence of inorganic and organic contaminants poses a significant threat to both the surrounding ecosystem and public health. However, the migration characteristics of these co-contaminants within the soil and their interactions with key components, including Fe-bearing minerals, organic matter, and microorganisms, remain unclear. This study involved the collection of a 4.3-m-depth co-contaminated soil profile to investigate the vertical distribution patterns of co-contaminants (namely, arsenic, cadmium, and polychlorinated biphenyls (PCBs)) and their binding mechanisms with environmental factors. The results indicated a notable downward accumulation of inorganic contaminants with increasing soil depth, whereas PCBs were predominantly concentrated in the uppermost layer. Chemical extraction and synchrotron radiation analysis highlighted a positive correlation between the abundance of reactive iron (FeCBD) and both co-contaminants and microbial communities in the contaminated site. Furthermore, Mantel tests and structural equation modeling (SEM) demonstrated the direct impacts of FeCBD and microbial communities on co-contaminants within the soil profile. Overall, these results provided valuable insights into the migration and transformation characteristics of co-contaminants and their binding mechanisms mediated by minerals, organic matter, and microorganisms.
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Microbiota , Bifenilos Policlorados , Poluentes do Solo , Ferro/química , Solo/química , Bifenilos Policlorados/análise , Poluentes do Solo/análise , Minerais/químicaRESUMO
OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.
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Lúpus Eritematoso Sistêmico , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Seguimentos , Índice de Gravidade de Doença , Inquéritos e Questionários , Lúpus Eritematoso Sistêmico/psicologia , ChinaRESUMO
Human brain structure shows heterogeneous patterns of change across adults aging and is associated with cognition. However, the relationship between cortical structural changes during aging and gene transcription signatures remains unclear. Here, using structural magnetic resonance imaging data of two separate cohorts of healthy participants from the Cambridge Centre for Aging and Neuroscience (n = 454, 18-87 years) and Dallas Lifespan Brain Study (n = 304, 20-89 years) and a transcriptome dataset, we investigated the link between cortical morphometric similarity network and brain-wide gene transcription. In two cohorts, we found reproducible morphometric similarity network change patterns of decreased morphological similarity with age in cognitive related areas (mainly located in superior frontal and temporal cortices), and increased morphological similarity in sensorimotor related areas (postcentral and lateral occipital cortices). Changes in morphometric similarity network showed significant spatial correlation with the expression of age-related genes that enriched to synaptic-related biological processes, synaptic abnormalities likely accounting for cognitive decline. Transcription changes in astrocytes, microglia, and neuronal cells interpreted most of the age-related morphometric similarity network changes, which suggest potential intervention and therapeutic targets for cognitive decline. Taken together, by linking gene transcription signatures to cortical morphometric similarity network, our findings might provide molecular and cellular substrates for cortical structural changes related to cognitive decline across adults aging.
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Envelhecimento , Encéfalo , Adulto , Humanos , Encéfalo/fisiologia , Envelhecimento/fisiologia , Cognição/fisiologia , Lobo Temporal , Imageamento por Ressonância Magnética/métodosRESUMO
Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.
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Transtorno Bipolar , Humanos , Criança , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/psicologia , Encéfalo/diagnóstico por imagem , Emoções/fisiologia , Lobo Frontal , Córtex Pré-Frontal , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
Brain function changes affect cognitive functions in older adults, yet the relationship between cognition and the dynamic changes of brain networks during naturalistic stimulation is not clear. Here, we recruited the young, middle-aged and older groups from the Cambridge Center for Aging and Neuroscience to investigate the relationship between dynamic metrics of brain networks and cognition using functional magnetic resonance imaging data during movie-watching. We found six reliable co-activation pattern (CAP) states of brain networks grouped into three pairs with opposite activation patterns in three age groups. Compared with young and middle-aged adults, older adults dwelled shorter time in CAP state 4 with deactivated default mode network (DMN) and activated salience, frontoparietal and dorsal-attention networks (DAN), and longer time in state 6 with deactivated DMN and activated DAN and visual network, suggesting altered dynamic interaction between DMN and other brain networks might contribute to cognitive decline in older adults. Meanwhile, older adults showed easier transfer from state 6 to state 3 (activated DMN and deactivated sensorimotor network), suggesting that the fragile antagonism between DMN and other cognitive networks might contribute to cognitive decline in older adults. Our findings provided novel insights into aberrant brain network dynamics associated with cognitive decline.
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Encéfalo , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Cognição/fisiologia , Mapeamento Encefálico , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologiaRESUMO
The objective of this study was to evaluate the worldwide burden of leukemia owing to occupational exposure to formaldehyde (OEF) from 1990 to 2019. Data on leukemia due to OEF were obtained from the Global Burden of Disease Study (GBD) 2019. By region, age, sex, and disease subtype, the numbers and age-standardized rates (ASRs) associated with deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed. Annual average percentage change (AAPC) was used to estimate disease burden trends from 1990 to 2019. To measure the risk of leukemia due to OEF, the population attributable fraction (PAF) was introduced. From 1990 to 2019, the number of deaths, DALYs, YLLs, and YLDs for leukemia caused by OEF increased by 44%, 34%, 33%, and 124%, respectively. Regarding the change in ASRs, the age-standardized YLDs (ASYLDs) rate of leukemia due to OEF, which was 38.03% (AAPC = 1.17 [95% confidence interval [CI] 1.11, 1.23]), indicated an increased trend. But the age-standardized mortality rate (ASMR), age-standardized DALY (ASDALY) rate, and age-standardized YLL (ASYLL) rate showed decline trends, with - 11.90% (AAPC = - 0.41 [95% CI - 0.45, - 0.37]), - 14.19% (AAPC = - 0.5 [95% CI - 0.55, - 0.45]), and - 14.97% (AAPC = - 0.53 [95% CI - 0.58, - 0.48]), respectively. In terms of PAFs, there were increasing trends in PAFs of age-standardized deaths, ASDALYs, ASYLLs, and ASYLDs for leukemia caused by OEF, with 20.15% (95% uncertainty interval [UI] 11.76%, 30.25%), 36.28% (95% UI 21.46%, 53.42%), 51.91% (95% UI 35.05%, 72.07%), and 36.34% (95% UI 21.58%, 53.63%), respectively. Across the socio-demographic index (SDI) regions, the leukemia burden caused by OEF was concentrated in middle and high-middle SDI regions. Besides, OEF poses a more serious risk for acute leukemia among the leukemia subtype. Globally, leukemia caused by OEF remains a public health burden. Policies must be developed to avoid the burden of leukemia caused by OEF.
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Leucemia , Exposição Ocupacional , Humanos , Expectativa de Vida , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Leucemia/induzido quimicamente , Leucemia/epidemiologia , Saúde GlobalRESUMO
The potential host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been expanding alongside its evolution during the pandemic, with rabbits and hares being considered important potential hosts, supported by a report of rabbit sero-prevalence in nature. We measured the binding affinities of rabbit and hare angiotensin-converting enzyme 2 (ACE2) with receptor-binding domains (RBDs) from SARS-CoV, SARS-CoV-2, and its variants and found that rabbit and hare ACE2s had broad variant tropism, with significantly enhanced affinities to Omicron BA.4/5 and its subsequent-emerged sub-variants (>10 fold). The structures of rabbit ACE2 complexed with either SARS-CoV-2 prototype (PT) or Omicron BA.4/5 spike (S) proteins were determined, thereby unveiling the importance of rabbit ACE2 Q34 in RBD-interaction and elucidating the molecular basis of the enhanced binding with Omicron BA.4/5 RBD. These results address the highly enhanced risk of rabbits infecting SARS-CoV-2 Omicron sub-variants and the importance of constant surveillance.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the globe and caused immense health and economic damage. SARS-CoV-2 has demonstrated a broad host range, indicating a high risk of interspecies transmission and adaptive mutation. Therefore, constant monitoring for potential hosts is of immense importance. In this study, we found that Omicron BA.4/5 and subsequent-emerged sub-variants exhibited enhanced binding to both rabbit and hare angiotensin-converting enzyme 2 (ACE2), and we elucidated the structural mechanism of their recognition. From the structure, we found that Q34, a unique residue of rabbit ACE2 compared to other ACE2 orthologs, plays an important role in ACE2 recognition. These results address the probability of rabbits/hares being potential hosts of SARS-CoV-2 and broaden our knowledge regarding the molecular mechanism of SARS-CoV-2 interspecies transmission.
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COVID-19 , Lebres , Animais , Coelhos , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , Mutação , Glicoproteína da Espícula de Coronavírus/genética , Ligação ProteicaRESUMO
Osteoarthritis (OA) is a degenerative joint disease commonly found in middle-aged and older people. Chondrocytes are the only cells in joint cartilage that are difficult to heal after pyroptosis, and they will aggravate the wear and tear of joint cartilage and affect the progression of OA. Pyroptosis is a novel form of programmed cell death, and the classical pyroptosis pathway is a programmed cell death pattern mediated by inflammatory cysteine protease-1. Activation of NLRP3 leads to activation and cleavage of caspase-1 precursors, which in turn leads to activation and cleavage of GSDMD proteins and the release of proinflammatory factors. Resolvin D1 (RvD1) is a specialized pro-resolving mediator (SPM) derived from omega-3 unsaturated fatty acids that reduces inflammation and catabolic responses in OA chondrocytes. However, it is unclear whether RvD1 promotes OA chondrocyte proliferation and thus joint cartilage repair. Our results show that RvD1 regulates the NLRP3/caspase-1 signaling pathway by inhibiting the expression of caspase-1, promoting the proliferation of OA chondrocytes, promoting the repair of articular cartilage in rats and delaying the progression of osteoarthritis.
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Proteína 3 que Contém Domínio de Pirina da Família NLR , Osteoartrite , Humanos , Pessoa de Meia-Idade , Ratos , Animais , Idoso , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Condrócitos/metabolismo , Caspase 1/metabolismo , Osteoartrite/metabolismo , Transdução de Sinais , Proliferação de CélulasRESUMO
Intravoxel incoherent motion (IVIM) modeling is a widely used double-exponential model for describing diffusion-weighted imaging (DWI) signal, with a slow component related to pure molecular diffusion and a fast component associated with microcirculatory perfusion, which compensates for the limitations of traditional DWI. IVIM is a noninvasive technique for obtaining liver pathological information and characterizing liver lesions, and has potential applications in the initial diagnosis and treatment monitoring of liver diseases. Recent studies have demonstrated that IVIM-derived parameters are useful for evaluating liver lesions, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and liver tumors. However, the results are not stable. Therefore, it is necessary to summarize the current applications of IVIM in liver disease research, identify existing shortcomings, and point out the future development direction. In this review, we searched for studies related to hepatic IVIM-DWI applications over the past two decades in the PubMed database. We first introduce the fundamental principles and influential factors of IVIM, and then discuss its application in NAFLD, liver fibrosis, and focal hepatic lesions. It has been found that IVIM is still unstable in ensuring the robustness and reproducibility of measurements in the assessment of liver fibrosis grade and liver tumors differentiation, due to inconsistent and substantial overlap in the range of IVIM-derived parameters for different fibrotic stages. In the end, the future direction of IVIM-DWI in the assessment of liver diseases is discussed, emphasizing the need for further research on the stability of IVIM-derived parameters, particularly perfusion-related parameters, in order to promote the clinical practice of IVIM-DWI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.
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OBJECTIVES: The abrupt change of climate has led to an increasing trend of hospitalised patients in recent years. This study aimed to analyse the temperature variability (TV) associated with respiratory disease (RD) hospitalisations, hospital stays and hospital expenses. STUDY DESIGN: The generalized linear model combined with distributed lag non-linear model was used to investigate the association between TV and RD hospitalisations. METHODS: TV was determined by measuring the standard deviation of maximum and minimum temperatures for the current day and the previous 7 days. RD hospitalisations data were obtained from three major tertiary hospitals in Huaibei City, namely, the Huaibei People's Hospital, the Huaibei Hospital Of Traditional Chinese Medicine and the Huaibei Maternal and Child Health Care Hospital. First, using a time series decomposition model, the seasonality and long-term trend of hospitalisations, hospital stays and hospital expenses for RD were explored in this warm temperate sub-humid monsoon climate. Second, robust models were used to analyse the association between TV and RD hospitalisations, hospital stays and hospital expenses. In addition, this study stratified results by sex, age and season. Third, using the attributable fraction (AF) and attributable number (AN), hospitalisations, hospital stays and hospital expenses for RD attributed to TV were quantified. RESULTS: Overall, 0.013% of hospitalisations were attributed to TV0-1 (i.e. TV at the current day and previous 1 day), corresponding to 220 cases, 1603 days of hospital stays and 1,308,000 RMB of hospital expenses. Females were more susceptible to TV than males, and the risk increased with longer exposure (the highest risk was seen at TV0-7 [i.e. TV at the current day and previous 7 days] exposure). Higher AF and AN were observed at ages 0-5 years and ≥65 years. In addition, it was also found that TV was more strongly linked to RD in the cool season. The hot season was positively associated with hospital stays and hospital expenses at TV0-3 to TV0-7 exposure. CONCLUSIONS: Exposure to TV increased the risk of hospitalisations, longer hospital stays and higher hospital expenses for RD. The findings suggested that more attention should be paid to unstable weather conditions in the future to protect the health of vulnerable populations.