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1.
Cell ; 184(7): 1865-1883.e20, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636127

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. By using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep-learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our findings thus shed light on coronavirus and reveal multiple candidate therapeutics for COVID-19 treatment.


Assuntos
Tratamento Farmacológico da COVID-19 , Reposicionamento de Medicamentos , RNA Viral , Proteínas de Ligação a RNA/antagonistas & inibidores , SARS-CoV-2 , Animais , Linhagem Celular , Chlorocebus aethiops , Aprendizado Profundo , Humanos , Conformação de Ácido Nucleico , RNA Viral/química , Proteínas de Ligação a RNA/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética
2.
Proc Natl Acad Sci U S A ; 120(40): e2302484120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37769254

RESUMO

Two behavioral motivations coexist in transgressors following an interpersonal transgression-approaching and compensating the victim and avoiding the victim. Little is known about how these motivations arise, compete, and drive transgressors' decisions. The present study adopted a social interaction task to manipulate participants' (i.e., the transgressor) responsibility for another's (i.e., the victim) monetary loss and measure the participants' tradeoff between compensating the victim and avoiding face-to-face interactions with the victim. Following each transgression, participants used a computer mouse to choose between two options differing in the amount of compensation to the victim and the probability of face-to-face contact with the victim. Results showed that as participants' responsibility increased, 1) the decision weights on contact avoidance relative to compensation increased, and 2) the onset of the contact-avoidance attribute was expedited and that of the compensation attribute was delayed. These results demonstrate how competing social motivations following transgression evolve and determine social decision-making and shed light on how social-affective state modulates the dynamics of decision-making in general.


Assuntos
Emoções , Motivação , Humanos , Comportamento Social , Interação Social , Relações Interpessoais
3.
PLoS Comput Biol ; 20(6): e1011882, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838038

RESUMO

In embryonic development and organogenesis, cells sharing identical genetic codes acquire diverse gene expression states in a highly reproducible spatial distribution, crucial for multicellular formation and quantifiable through positional information. To understand the spontaneous growth of complexity, we constructed a one-dimensional division-decision model, simulating the growth of cells with identical genetic networks from a single cell. Our findings highlight the pivotal role of cell division in providing positional cues, escorting the system toward states rich in information. Moreover, we pinpointed lateral inhibition as a critical mechanism translating spatial contacts into gene expression. Our model demonstrates that the spatial arrangement resulting from cell division, combined with cell lineages, imparts positional information, specifying multiple cell states with increased complexity-illustrated through examples in C.elegans. This study constitutes a foundational step in comprehending developmental intricacies, paving the way for future quantitative formulations to construct synthetic multicellular patterns.


Assuntos
Redes Reguladoras de Genes , Modelos Biológicos , Animais , Redes Reguladoras de Genes/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/crescimento & desenvolvimento , Divisão Celular/fisiologia , Divisão Celular/genética , Biologia Computacional , Desenvolvimento Embrionário/fisiologia , Desenvolvimento Embrionário/genética , Linhagem da Célula , Simulação por Computador , Regulação da Expressão Gênica no Desenvolvimento/genética
4.
Proc Natl Acad Sci U S A ; 119(49): e2209078119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36445964

RESUMO

In the history of humanity, most conflicts within and between societies have originated from perceived inequality in resource distribution. How humans achieve and maintain distributive justice has therefore been an intensely studied issue. However, most research on the corresponding psychological processes has focused on inequality aversion and has been largely agnostic of other motives that may either align or oppose this behavioral tendency. Here we provide behavioral, computational, and neuroimaging evidence that distribution decisions are guided by three distinct motives-inequality aversion, harm aversion, and rank reversal aversion-that interact with each other and can also deter individuals from pursuing equality. At the neural level, we show that these three motives are encoded by separate neural systems, compete for representation in various brain areas processing equality and harm signals, and are integrated in the striatum, which functions as a crucial hub for translating the motives to behavior. Our findings provide a comprehensive framework for understanding the cognitive and biological processes by which multiple prosocial motives are coordinated in the brain to guide redistribution behaviors. This framework enhances our understanding of the brain mechanisms underlying equality-related behavior, suggests possible neural origins of individual differences in social preferences, and provides a new pathway to understand the cognitive and neural basis of clinical disorders with impaired social functions.


Assuntos
Motivação , Justiça Social , Humanos , Encéfalo , Ciências Humanas , Afeto
5.
Neuroimage ; 285: 120468, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38042393

RESUMO

When confronted with injustice, individuals often intervene as third parties to restore justice by either punishing the perpetrator or helping the victim, even at their own expense. However, little is known about how individual differences in third-party intervention propensity are related to inter-individual variability in intrinsic brain connectivity patterns and how these associations vary between help and punishment intervention. To address these questions, we employed a novel behavioral paradigm in combination with resting-state fMRI and inter-subject representational similarity analysis (IS-RSA). Participants acted as third-party bystanders and needed to decide whether to maintain the status quo or intervene by either helping the disadvantaged recipient (Help condition) or punishing the proposer (Punish condition) at a specific cost. Our analyses focused on three brain networks proposed in the third-party punishment (TPP) model: the salience (e.g., dorsal anterior cingulate cortex, dACC), central executive (e.g., dorsolateral prefrontal cortex, dlPFC), and default mode (e.g., dorsomedial prefrontal cortex, dmPFC; temporoparietal junction, TPJ) networks. IS-RSA showed that individual differences in resting-state functional connectivity (rs-FC) patterns within these networks were associated with the general third-party intervention propensity. Moreover, rs-FC patterns of the right dlPFC and right TPJ were more strongly associated with individual differences in the helping propensity rather than the punishment propensity, whereas the opposite pattern was observed for the dmPFC. Post-hoc predictive modeling confirmed the predictive power of rs-FC in these regions for intervention propensity across individuals. Collectively, these findings shed light on the shared and distinct roles of key regions in TPP brain networks at rest in accounting for individual variations in justice-restoring intervention behaviors.


Assuntos
Encéfalo , Córtex Pré-Frontal , Humanos , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância Magnética
6.
Cereb Cortex ; 33(17): 9741-9755, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37415070

RESUMO

The human brain can utilize various information to form temporal expectations and optimize perceptual performance. Here we show dissociated amplitude and phase effects of prestimulus alpha oscillation in a nested structure of rhythm- and sequence-based expectation. A visual stream of rhythmic stimuli was presented in a fixed sequence such that their temporal positions could be predicted by either the low-frequency rhythm, the sequence, or the combination. The behavioral modeling indicated that rhythmic and sequence information additively led to increased accumulation speed of sensory evidence and alleviated threshold for the perceptual discrimination of the expected stimulus. The electroencephalographical results showed that the alpha amplitude was modulated mainly by rhythmic information, with the amplitude fluctuating with the phase of the low-frequency rhythm (i.e. phase-amplitude coupling). The alpha phase, however, was affected by both rhythmic and sequence information. Importantly, rhythm-based expectation improved the perceptual performance by decreasing the alpha amplitude, whereas sequence-based expectation did not further decrease the amplitude on top of rhythm-based expectation. Moreover, rhythm-based and sequence-based expectations collaboratively improved the perceptual performance by biasing the alpha oscillation toward the optimal phase. Our findings suggested flexible coordination of multiscale brain oscillations in dealing with a complex environment.


Assuntos
Eletroencefalografia , Motivação , Humanos , Encéfalo , Ritmo alfa , Estimulação Luminosa/métodos
7.
Cereb Cortex ; 33(9): 5671-5689, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36437790

RESUMO

Linguistic communication is often regarded as an action that serves a function to convey the speaker's goal to the addressee. Here, with an functional magnetic resonance imaging (fMRI) study and a lesion study, we demonstrated that communicative functions are represented in the human premotor cortex. Participants read scripts involving 2 interlocutors. Each script contained a critical sentence said by the speaker with a communicative function of either making a Promise, a Request, or a Reply to the addressee's query. With various preceding contexts, the critical sentences were supposed to induce neural activities associated with communicative functions rather than specific actions literally described by these sentences. The fMRI results showed that the premotor cortex contained more information, as revealed by multivariate analyses, on communicative functions and relevant interlocutors' attitudes than the perisylvian language regions. The lesion study results showed that, relative to healthy controls, the understanding of communicative functions was impaired in patients with lesions in the premotor cortex, whereas no reliable difference was observed between the healthy controls and patients with lesions in other brain regions. These findings convergently suggest the crucial role of the premotor cortex in representing the functions of linguistic communications, supporting that linguistic communication can be seen as an action.


Assuntos
Córtex Motor , Humanos , Idioma , Linguística , Comunicação , Encéfalo , Imageamento por Ressonância Magnética
8.
Cereb Cortex ; 33(22): 11126-11145, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37814363

RESUMO

Early auditory deprivation leads to a reorganization of large-scale brain networks involving and extending beyond the auditory system. It has been documented that visuomotor transformation is impaired after early deafness, associated with a hyper-crosstalk between the task-critical frontoparietal network and the default-mode network. However, it remains unknown whether and how the reorganized large-scale brain networks involving the auditory cortex contribute to impaired visuomotor transformation after early deafness. Here, we asked deaf and early hard of hearing participants and normal hearing controls to judge the spatial location of a visual target. Compared with normal hearing controls, the superior temporal gyrus showed significantly increased functional connectivity with the frontoparietal network and the default-mode network in deaf and early hard of hearing participants, specifically during egocentric judgments. However, increased superior temporal gyrus-frontoparietal network and superior temporal gyrus-default-mode network coupling showed antagonistic effects on egocentric judgments. In deaf and early hard of hearing participants, increased superior temporal gyrus-frontoparietal network connectivity was associated with improved egocentric judgments, whereas increased superior temporal gyrus-default-mode network connectivity was associated with deteriorated performance in the egocentric task. Therefore, the data suggest that the auditory cortex exhibits compensatory neuroplasticity (i.e. increased functional connectivity with the task-critical frontoparietal network) to mitigate impaired visuomotor transformation after early auditory deprivation.


Assuntos
Córtex Auditivo , Surdez , Perda Auditiva , Humanos , Córtex Auditivo/diagnóstico por imagem , Mapeamento Encefálico , Encéfalo , Lobo Temporal/diagnóstico por imagem , Imageamento por Ressonância Magnética
9.
Skin Res Technol ; 30(3): e13629, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38407525

RESUMO

PURPOSE: Although many studies have investigated the association between psoriasis and chronic obstructive pulmonary disease (COPD), the causal relationship between psoriasis and COPD is still unknown. METHODS: We employed bidirectional Mendelian randomization to investigate the causal relationship between psoriasis and COPD. Genetic instruments for exposure were selected from two distinct genome-wide association study databases. Single nucleotide polymorphisms associated with exposures at the genome-wide significance level (p < 5 × 10^-8 ) and exhibiting low linkage disequilibrium (r^2  < 0.001) were chosen as instrumental variables. Causality was assessed using multiple MR methods, including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. A significance level of p < 0.05 was considered statistically significant. Heterogeneity was examined using Cochran's Q test, and MR-Egger regression was employed to detect pleiotropy. The robustness and reliability of the results were further evaluated through leave-one-out analysis. RESULTS: We found a positive causal association between psoriasis and COPD [IVW: odds ratio (OR): 1.0006; p = 0.0056]. Heterogeneity and pleiotropy have not been discovered, so the results of the study are reliable. In the reverse analysis, no causal association between CPOD and psoriasis was found. CONCLUSION: Our findings revealed that psoriasis was associated with an elevated risk of COPD. However, no causal association between COPD and psoriasis was identified in our study.


Assuntos
Psoríase , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Psoríase/epidemiologia , Psoríase/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética
10.
Skin Res Technol ; 30(7): e13781, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38932454

RESUMO

BACKGROUND: Reports suggest that lipid profiles may be linked to the likelihood of developing skin cancer, yet the exact causal relationship is still unknown. OBJECTIVE: This study aimed to examine the connection between lipidome and skin cancers, as well as investigate any possible mediators. METHODS: A two-sample Mendelian randomization (MR) analysis was conducted on 179 lipidomes and each skin cancer based on a genome-wide association study (GWAS), including melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Then, Bayesian weighted MR was performed to verify the analysis results of two-sample MR. Moreover, a two-step MR was employed to investigate the impact of TNF-like weak inducer of apoptosis (TWEAK)-mediated lipidome on skin cancer rates. RESULTS: MR analysis identified higher genetically predicted phosphatidylcholine (PC) (17:0_18:2) could reduce the risk of skin tumors, including BCC (OR = 0.9149, 95% CI: 0.8667-0.9658), SCC (OR = 0.9343, 95% CI: 0.9087-0.9606) and melanoma (OR = 0.9982, 95% CI: 0.9966-0.9997). The proportion of PC (17:0_18:2) predicted by TWEAK-mediated genetic prediction was 6.6 % in BCC and 7.6% in SCC. The causal relationship between PC (17:0_18:2) and melanoma was not mediated by TWEAK. CONCLUSION: This study identified a negative causal relationship between PC (17:0_18:2) and keratinocyte carcinomas, a small part of which was mediated by TWEAK, and most of the remaining mediating factors are still unclear. Further research on other risk factors is needed in the future.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Citocina TWEAK , Queratinócitos , Lipidômica , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Citocina TWEAK/genética , Citocina TWEAK/metabolismo , Queratinócitos/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudo de Associação Genômica Ampla , Melanoma/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença/genética , Teorema de Bayes
11.
Psychol Res ; 88(2): 404-416, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37498337

RESUMO

Reward motivates goal-directed behaviors, leading to faster reaction time (RT) and lower error rate in searching for a target in the reward condition than in the no-reward condition in target-discrimination tasks. However, it is unclear how reward influences target detection in which participants are required to judge whether a predesignated target is present or absent. Here, we asked participants to complete a target-detection search task in which the color of the search array indicated the reward availability of the current trial. Correct and faster (than a baseline) responses would be rewarded if the search array had the reward-related color. In Experiments 1A and 1B, the target was presented in 50% of the trials. Experiment 1B had the same design as Experiment 1A, except that different baselines were set for the target-present and target-absent conditions. In Experiment 2, the proportion of target presence was manipulated to be high (80%), moderate (50%), or low (20%) in different blocks of stimuli. Results showed that, across all the experiments, participants responded faster and made fewer errors in the reward than in the no-reward condition when the target was present. However, this facilitatory effect was reversed when the target was absent, showcasing a reward-induced interference. The signal detection analysis suggested that reward biased the report criterion to the "yes" response. These findings demonstrate that the impact of reward on goal-directed behavior can be detrimental and reward prolongs the search process by rendering participants reluctant to say "no" in visual search termination.


Assuntos
Recompensa , Humanos , Tempo de Reação/fisiologia
12.
BMC Med Educ ; 24(1): 596, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816806

RESUMO

BACKGROUND: The shortage of pathologists in Germany, coupled with an aging workforce, requires innovative approaches to attract medical students to the field. Medical education must address different learning styles to ensure that all students are successful. METHODS: The pilot project "Practical Pathology" aims to enhance students' understanding of pathology by providing hands-on experience in macroscopic gross analysis through the use of tumor dummies built from scratch. RESULTS: An evaluation survey, completed by 63 participating students provided positive feedback on the course methodology, its relevance to understanding the pathology workflow, and its improvement over traditional teaching methods. The majority of students recognized the importance of hands-on training in medical education. Students with previous work experience rated the impact of the course on knowledge acquisition even more positively. CONCLUSION: The course improved students' understanding of pathological processes and potential sources of clinical-pathological misunderstanding. An increase in motivation for a potential career in the field of pathology was observed in a minority of students, although this exceeded the percentage of pathologists in the total medical workforce.


Assuntos
Patologia , Estudantes de Medicina , Humanos , Projetos Piloto , Estudantes de Medicina/psicologia , Patologia/educação , Alemanha , Competência Clínica , Neoplasias/patologia , Educação de Graduação em Medicina , Ensino , Currículo , Patologistas/educação , Masculino , Feminino
13.
Plant Foods Hum Nutr ; 79(2): 308-315, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639852

RESUMO

In food industry, the characteristics of food substrate could be improved through its bidirectional solid-state fermentation (BSF) by fungi, because the functional components were produced during BSF. Six edible fungi were selected for BSF to study their effects on highland barley properties, such as functional components, antioxidant activity, and texture characteristics. After BSF, the triterpenes content in Ganoderma lucidum and Ganoderma leucocontextum samples increased by 76.57 and 205.98%, respectively, and the flavonoids content increased by 62.40% (Phellinus igniarius). Protein content in all tests increased significantly, with a maximal increase of 406.11% (P. igniarius). Proportion of indispensable amino acids increased significantly, with the maximum increase of 28.22%. Lysine content increased largest by 437.34% to 3.310 mg/g (Flammulina velutipes). For antioxidant activity, ABTS radical scavenging activity showed the maximal improvement, with an increase of 1268.95%. Low-field NMR results indicated a changed water status of highland barley after fermentation, which could result in changes in texture characteristics of highland barley. Texture analysis showed that the hardness and chewiness of the fermented product decreased markedly especially in Ganoderma lucidum sample with a decrease of 77.96% and 58.60%, respectively. The decrease indicated a significant improvement in the taste of highland barley. The results showed that BSF is an effective technology to increase the quality of highland barley and provide a new direction for the production of functional foods.


Assuntos
Antioxidantes , Fermentação , Ganoderma , Hordeum , Hordeum/química , Antioxidantes/análise , Antioxidantes/metabolismo , Ganoderma/química , Ganoderma/metabolismo , Flavonoides/análise , Aminoácidos/análise , Aminoácidos/metabolismo , Flammulina/química , Flammulina/metabolismo , Reishi/metabolismo , Reishi/química , Manipulação de Alimentos/métodos
14.
Opt Express ; 31(1): 426-441, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606977

RESUMO

Photon counting is a promising solution to detecting low-power optical signals for ultraviolet (UV) communications in the forthcoming sixth-generation (6G) network. Different from the conventional additive white Gaussian noise (AWGN) model, the discrete signal-dependent Poisson shot noise poses challenges to the signal processing of photon-counting systems. In this paper, a joint design of precoder and equalizer is proposed for photon-counting multiple-input multiple-output (PhC-MIMO) UV systems. To circumvent the impasse arising from the signal-dependent shot noise, we propose an alternating optimization algorithm based on the minimum mean squared error (MMSE) criterion. The algorithm decomposes the joint design into convex subproblems solved in an alternating manner, and guarantees at least a stationary point solution. Numerical results corroborate that the proposed system exhibits robustness to turbulence fading and offers high throughput while mitigating the adverse effect of background radiation noise. Specifically, the 32 × 8 system can achieve a bit error rate (BER) of 10-5 at the signal energy of -154.0 dBJ per bit under strong Gamma-Gamma turbulence with the scintillation index (S.I.) of 3.

15.
Psychol Med ; 53(12): 5569-5581, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36066201

RESUMO

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is a high-prevalence personality disorder characterized by subtle but stable interpersonal dysfunction. There have been only limited studies addressing the behavioral patterns and cognitive features of OCPD in interpersonal contexts. The purpose of this study was to investigate how behaviors differ between OCPD individuals and healthy controls (HCs) in the context of guilt-related interpersonal responses. METHOD: A total of 113 participants were recruited, including 46 who were identified as having OCPD and 67 HCs. Guilt-related interpersonal responses were manipulated and measured with two social interactive tasks: the Guilt Aversion Task, to assess how anticipatory guilt motivates cooperation; and the Guilt Compensation Task, to assess how experienced guilt induces compensation behaviors. The guilt aversion model and Fehr-Schmidt inequity aversion model were adopted to analyze decision-making in the Guilt Aversion Task and the Guilt Compensation Task, respectively. RESULTS: Computational model-based results demonstrated that, compared with HCs, the OCPD group exhibited less guilt aversion when making cooperative decisions as well as less guilt-induced compensation after harming others. CONCLUSION: Our findings indicate that individuals with OCPD tend to be less affected by guilt than HCs. These impairments in guilt-related responses may prevent adjustments in behaviors toward compliance with social norms and thus result in interpersonal dysfunctions.


Assuntos
Transtorno da Personalidade Compulsiva , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno da Personalidade Compulsiva/psicologia , Transtorno Obsessivo-Compulsivo/psicologia , Interação Social , Culpa , Simulação por Computador
16.
J Surg Res ; 285: 158-167, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680876

RESUMO

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.


Assuntos
Traumatismos por Explosões , Hemostáticos , Animais , Coelhos , Fibrinogênio , Hemostasia , Derivados de Hidroxietil Amido , Reprodutibilidade dos Testes , Ressuscitação/métodos
17.
Immunol Invest ; 52(6): 767-778, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37417317

RESUMO

BACKGROUND: Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. METHODS: In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. RESULTS: The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070-4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025). CONCLUSION: The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.


Assuntos
Antígenos HLA-A , Hepatite B , Adulto , Humanos , Alelos , China , População do Leste Asiático , Frequência do Gene , Predisposição Genética para Doença , Hepatite B/genética , Vírus da Hepatite B , Antígenos HLA-A/genética , Antígenos HLA-B , Cadeias HLA-DRB1/genética
18.
Exp Cell Res ; 410(1): 112951, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843715

RESUMO

Endoreplication, known as endocycles or endoreduplication, is a cell cycle variant in which the genomic DNA is re-replicated without mitosis leading to polyploidy. Endoreplication is essential for the development and functioning of the different organs in animals and plants. Deletion of Geminin, a DNA replication licensing inhibitor, causes DNA re-replication or damage. However, the role of Geminin in endoreplication is still unclear. Here, we studied the role of Geminin in the endoreplication of the silk gland cells of silkworms by constructing two transgenic silkworm strains, including BmGeminin1-overexpression and BmGeminin1-RNA interference. Interference of BmGeminin1 led to body weight gain, increased silk gland volume, increased DNA content, and enhanced DNA re-replication activity relative to wild-type Dazao. Meanwhile, overexpression of BmGeminin1 showed an opposite phenotype compared to the BmGem1-RNAi strain. Furthermore, RNA-sequencing of the transgenic strains was carried out to explore how BmGeminin1 regulates DNA re-replication. Our data demonstrated a vital role of Geminin in the regulation of endoreplication in the silk gland of silkworms.


Assuntos
Bombyx/genética , Replicação do DNA/genética , Geminina/genética , Seda/genética , Animais , Bombyx/metabolismo , Ciclo Celular/genética , Geminina/antagonistas & inibidores , Mitose/genética , Interferência de RNA , Seda/biossíntese
19.
Environ Res ; 220: 115241, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621547

RESUMO

Large volumes of iron-containing sludge (Fe-Sludge) would be generated with the application of iron salts in drinking water treatment plants, which must be disposed appropriately. One of the common disposal solutions for Fe-Sludge is through direct disposal into the municipal sewer system, whereby it would be mixed with domestic wastewater and treated in the wastewater treatment plant. To better understand the properties of Fe-Sludge and the effect of dosing Fe-Sludge to the real domestic wastewater (WW) on the wastewater characteristics, a serial batch tests were conducted on a local wastewater reclamation plant (WRP). It was found that the impact of dosing Fe-Sludge at a Fe/P ratio of 5 did not vary with the types of WW, i.e., filtered or non-filtered by the 5 mm screen. In addition, the soluble organic, phosphate and total soluble iron concentrations mostly decreased with the dosing of Fe-Sludge within the dosage range of 0-5 (Fe/P ratio). In contrast, the suspended solid (SS) and volatile suspended solid (VSS) concentrations increased with the dosage of Fe-Sludge within the dosage range of 0-5 (Fe/P ratio). Furthermore, the pH condition of the domestic wastewater affected the phosphate removal efficiency by Fe-Sludge and influenced the total soluble iron concentration and iron species distribution. These findings will provide fundamental support for the further study of the effect of Fe-Sludge on the biological treatment performance and membrane filtration performance of the membrane bioreactor (MBR) system.


Assuntos
Esgotos , Águas Residuárias , Ferro/química , Eliminação de Resíduos Líquidos , Fosfatos/química , Reatores Biológicos , Concentração de Íons de Hidrogênio
20.
Nucleic Acids Res ; 49(D1): D183-D191, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33068412

RESUMO

RNA molecules fold into complex structures that are important across many biological processes. Recent technological developments have enabled transcriptome-wide probing of RNA secondary structure using nucleases and chemical modifiers. These approaches have been widely applied to capture RNA secondary structure in many studies, but gathering and presenting such data from very different technologies in a comprehensive and accessible way has been challenging. Existing RNA structure probing databases usually focus on low-throughput or very specific datasets. Here, we present a comprehensive RNA structure probing database called RASP (RNA Atlas of Structure Probing) by collecting 161 deduplicated transcriptome-wide RNA secondary structure probing datasets from 38 papers. RASP covers 18 species across animals, plants, bacteria, fungi, and also viruses, and categorizes 18 experimental methods including DMS-seq, SHAPE-Seq, SHAPE-MaP, and icSHAPE, etc. Specially, RASP curates the up-to-date datasets of several RNA secondary structure probing studies for the RNA genome of SARS-CoV-2, the RNA virus that caused the on-going COVID-19 pandemic. RASP also provides a user-friendly interface to query, browse, and visualize RNA structure profiles, offering a shortcut to accessing RNA secondary structures grounded in experimental data. The database is freely available at http://rasp.zhanglab.net.


Assuntos
Biologia Computacional/estatística & dados numéricos , Bases de Dados Genéticas/estatística & dados numéricos , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Conformação de Ácido Nucleico , RNA/química , Transcriptoma , Animais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Biologia Computacional/métodos , Genoma Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pandemias , RNA/genética , Sondas RNA/genética , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Fúngico/química , RNA Fúngico/genética , RNA de Plantas/química , RNA de Plantas/genética , RNA Viral/química , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
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