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The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.
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Galinhas , Animais , Dioxinas e Compostos Semelhantes a Dioxinas/metabolismo , Dioxinas e Compostos Semelhantes a Dioxinas/toxicidade , Feminino , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Bifenilos Policlorados/toxicidade , Metabolômica , Metaboloma/efeitos dos fármacos , Ração Animal/análise , Dibenzodioxinas Policloradas/toxicidadeRESUMO
Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
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Compostos Benzidrílicos , Galinhas , Estresse do Retículo Endoplasmático , Ferroptose , Fenóis , Piroptose , Espécies Reativas de Oxigênio , Selênio , Animais , Compostos Benzidrílicos/toxicidade , Ferroptose/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Selênio/deficiência , Fenóis/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Timo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.
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Bisphenol A (BPA) is widely applied in plastic products, which will produce immunotoxicity to organisms after spilling in the environment, and become a kind of endocrine disruptor. Selenium (Se) is an essential trace element and plays an important role in maintaining redox homeostasis and immune function. BPA exposure and Se deficiency often occur together in livestock and poultry farming, however, studies on the effects of joint exposure on chicken immunotoxins have not been reported. Therefore, this study established a chicken spleen and MDCC-MSB1 cell model under the combined effects of BPA exposure or/and Se deficiency. Transcriptomic analysis showed that BPA exposure and/or Se deficiency induced differential enrichment of positive regulatory pathways such as NLRP3 inflammatory complex assembly, inflammatory response and cellular oxidative stress response. In the -Se+BPA group, pathological damage was significantly increased, Se content decreased, BPA accumulation, oxidative stress and pyroptosis. Meanwhile, the roles and mechanisms of oxidative stress and pyroptosis in BPA exposure or/and Se deficiency-induced splenic tissue injury were investigated by using IF and qRT-PCR methods. The results showed that joint BPA exposure with Se deficiency resulted in more significant changes in the above outcomes than 1 of them. The oxidative stress inhibitor NAC effectually reduced Se deficiency and BPA-induced oxidative stress and pyroptosis, further suggests that oxidative stress mediated Se deficiency or/and BPA-induced pyroptosis. This study revealed that BPA exposure and Se deficiency induced spleen pyroptosis in chickens via the ROS/NLRP3 pathway. These results provide the theoretical basis for the toxicity of BPA in poultry and enrich the toxicological mechanism of combined exposure of Se deficiency and environmental toxins.
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Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.
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Apoptose , Proliferação de Células , Proteínas RGS , Saponinas , Transdução de Sinais , Espirostanos , Carcinoma Anaplásico da Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Saponinas/farmacologia , Proteínas RGS/metabolismo , Proteínas RGS/genética , Proliferação de Células/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Espirostanos/farmacologia , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Camundongos Nus , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Metástase NeoplásicaRESUMO
Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals.
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Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.
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Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135⯵M DEHP and/or 80⯵M Que were used to treat the IPEC-J2 cells for 24â¯h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H2O2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-ß, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells.
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Background: Cinnamomum camphora is a commercially important tree species in China, and it's also a common native tree in the forests of southern China. However, literature on the impact of Cinnamomum camphora essential oil (CCEO) on human psychophysiological activity is scarce. Hence, the primary objective of this study was to examine the effect of exposure to CCEO on the functioning of the human autonomic nervous system, electroencephalographic (EEG) activity, and emotional state. Methods: Forty-three healthy university students participated. The data collected included heart rate (HR), blood pressure (BP), pulse rate, blood oxygen saturation (SpO2), electroencephalographic (EEG) activity, and the results of the Profile of Mood States (POMS) test. Results: A drop in diastolic pressure (DBP) and pulse rate was also noticed after participants inhaled CCEO. Furthermore, EEG studies have demonstrated notable reductions in absolute beta (AB), absolute gamma (AG), absolute high beta (AHB), and relative gamma (RG) power spectra during exposure to CCEO. Conversely, the relative theta (RT) and power spectra values showed a significant increase. Additionally, the finding from POMS indicated that the fragrance evoked positive emotions and suppressed negative feelings. Conclusion: The results suggest that exposure to CCEO may promote mental and physical relaxation, facilitate cognitive processes such as memory and attention, and enhance mood states.
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Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.
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BACKGROUND: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. METHODS: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method. RESULTS: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. CONCLUSION: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.
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The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.
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Regulação da Expressão Gênica de Plantas , Família Multigênica , Panax , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Panax/genética , Panax/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Regiões Promotoras Genéticas , Perfilação da Expressão GênicaRESUMO
Family environment, emotion regulation and biological sensitivity have been shown to be associated with adolescents' externalizing problem behaviours. However, findings regarding respiratory sinus arrhythmia (RSA) reactivity are mixed and sometimes contradictory. This study aims to clarify the roles of RSA reactivity and anger regulation in the relationship between negative family expressiveness (NFE) and adolescents' externalizing behaviour by measuring RSA reactivity during the Parent-Adolescent Interaction Task (PAIT), designed to simulate a naturalistic negative family environment. In this study, 125 Chinese adolescents (M = 13.95 years, SD = 0.95; 48% male) completed questionnaires assessing negative family expressiveness, anger regulation and externalizing problems. Additionally, we collected electrocardiogram and respiration data during both the resting period and a 10-min PAIT. Results showed that anger regulation mediated the relationship between NFE and externalizing problem behaviours. Moreover, adolescents' RSA reactivity moderated this mediation effect, even after controlling for baseline RSA. Greater RSA suppression potentially indicated greater susceptibility, with the relationship between NFE and anger regulation being more pronounced in adolescents with greater RSA suppression compared to those with lesser RSA suppression. These findings highlight the importance of considering physiological systems, especially within the context of adverse family environments, when studying the relationships with externalizing problems.
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Path planning is an crucial research area in robotics. Compared to other path planning algorithms, the Rapidly-exploring Random Tree (RRT) algorithm possesses both search and random sampling properties, and thus has more potential to generate high-quality paths that can balance the global optimum and local optimum. This paper reviews the research on RRT-based improved algorithms from 2021 to 2023, including theoretical improvements and application implementations. At the theoretical level, branching strategy improvement, sampling strategy improvement, post-processing improvement, and model-driven RRT are highlighted, at the application level, application scenarios of RRT under welding robots, assembly robots, search and rescue robots, surgical robots, free-floating space robots, and inspection robots are detailed, and finally, many challenges faced by RRT at both the theoretical and application levels are summarized. This review suggests that although RRT-based improved algorithms has advantages in large-scale scenarios, real-time performance, and uncertain environments, and some strategies that are difficult to be quantitatively described can be designed based on model-driven RRT, RRT-based improved algorithms still suffer from the problems of difficult to design the hyper-parameters and weak generalization, and in the practical application level, the reliability and accuracy of the hardware such as controllers, actuators, sensors, communication, power supply and data acquisition efficiency all pose challenges to the long-term stability of RRT in large-scale unstructured scenarios. As a part of autonomous robots, the upper limit of RRT path planning performance also depends on the robot localization and scene modeling performance, and there are still architectural and strategic choices in multi-robot collaboration, in addition to the ethics and morality that has to be faced. To address the above issues, I believe that multi-type robot collaboration, human-robot collaboration, real-time path planning, self-tuning of hyper-parameters, task- or application-scene oriented algorithms and hardware design, and path planning in highly dynamic environments are future trends.
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Background: Numerous studies have consistently demonstrated a decline in sleep quality during the COVID-19 pandemic. The primary objective of this study is to explore the impact of engaging with pertinent epidemic information through the media amid the COVID-19 crisis on individuals' sleep quality and the underlying mechanisms through which this influence operates. Methods: An online cross-sectional study design was employed. A total of 1,063 British adults (36.2% males; M age = 38.85, SD age = 13.36, ranging from 18 to 77 years old) participated in the study and completed our questionnaires, which included media usage frequency during the pandemic, the 10-item Kessler Psychological Distress Scale (K10), the Insomnia Severity Index (ISI), and the Ten-item Personality Inventory (TIPI). Results: Pearson's correlation analyses indicated that there was no significant correlation between COVID-19-related traditional media use (television, radio, newspaper) and psychological distress or sleep quality. However, exposure to information related to COVID-19 through new media use (Facebook, Tik Tok, Twitter) was correlated with greater psychological distress and poorer sleep quality. A moderated mediation analysis showed that psychological distress fully mediated the relationship between new media use and poor sleep, which was moderated by age, with the association between psychological distress and poor sleep quality being stronger among older adults. Conclusion: Exposure to information of COVID-19 via new (but not traditional) media use deteriorated sleep quality through greater psychological distress, and this relationship was stronger among older adults.
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With the increasing production and demand of plastic products in life, inescapable bisphenol A (BPA) exposure results in a threat to the health of organisms. Selenium (Se) is an essential trace element for living organisms. The insufficient Se intake can cause multi-tissue organ damage. In the process of production and life, the exposure of BPA is usually accompanied by Se deficiency. In this study, the models of chicken with BPA exposure and/or Se deficiency was duplicated, the status of nitrification stress, apoptosis, necroptosis, and changes in TNF-α/FADD signaling pathways in chicken spleen were examined. At the same time, nitrification stress inhibitor and TNF-α inhibitor were introduced into MSB-1 cell model tests in vitro, indicating that BPA exposure and Se deficiency up-regulated TNF-α/FADD signaling pathway through nitrification stress, inducing necroptosis and apoptosis, and heat shock protein was also involved in this process. This study provides a new control idea for healthy poultry breeding based on Se, and also provides a new reference for toxicity control of environmental pollutants.
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Galinhas , Nitrificação , Fenóis , Baço , Fator de Necrose Tumoral alfa , Animais , Fator de Necrose Tumoral alfa/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Fenóis/toxicidade , Selênio/deficiência , Compostos Benzidrílicos/toxicidade , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.IMPORTANCEPhloroglucinol is an important intermediate in the bacterial degradation of polyphenols, a highly abundant class of plant natural products. Recent research has identified key enzymes of the phloroglucinol degradation pathway in butyrate-producing anaerobic bacteria, which involves cleavage of a linear triketide intermediate by a beta ketoacid cleavage enzyme, requiring acetyl-CoA as a co-substrate. This paper reports a variant of the pathway in the lactic acid bacterium Collinsella sp. zg1085, which involves cleavage of the triketide intermediate by a homolog of deoxyribose-5-phosphate aldolase, highlighting the variety of mechanisms for phloroglucinol degradation by different anaerobic bacterial taxa.
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Redes e Vias Metabólicas , Floroglucinol , Floroglucinol/metabolismo , Floroglucinol/análogos & derivados , Redes e Vias Metabólicas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Aldeído Liases/metabolismo , Aldeído Liases/genética , AnimaisRESUMO
Pseudorabies viruses (PRV) pose a major threat to the global pig industry and public health. Rapid, intuitive, affordable, and accurate diagnostic testing is critical for controlling and eradicating infectious diseases. In this study, a portable detection platform based on RPA-CRISPR/EsCas13d was developed. The platform exhibits high sensitivity (1 copy/µL), good specificity, and no cross-reactivity with common pathogens. The platform uses rapid preamplification technology to provide visualization results (lateral flow assays or visual fluorescence) within 1 h. Fifty pig samples (including tissues, oral fluids, and serum) were tested using this platform and real-time quantitative polymerase chain reaction (qPCR), showing 34.0 % (17 of 50) PRV positivity with the portable CRISPR/EsCas13d dual-readout platform, consistent with the qPCR results. These results highlight the stability, sensitivity, efficiency, and low equipment requirements of the portable platform. Additionally, a novel point-of-care test is being developed for clinical use in remote rural and resource-limited areas, which could be a prospective measure for monitoring the progression of pseudorabies and other infectious diseases worldwide.
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Sistemas CRISPR-Cas , Herpesvirus Suídeo 1 , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/isolamento & purificação , Animais , Suínos , Sistemas CRISPR-Cas/genética , Pseudorraiva/diagnóstico , Pseudorraiva/virologia , Doenças dos Suínos/virologia , Doenças dos Suínos/diagnósticoRESUMO
Graph Convolutional Networks (GCNs) are widely used for skeleton-based action recognition and achieved remarkable performance. Due to the locality of graph convolution, GCNs can only utilize short-range node dependencies but fail to model long-range node relationships. In addition, existing graph convolution based methods normally use a uniform skeleton topology for all frames, which limits the ability of feature learning. To address these issues, we present the Graph Convolution Network with Self-Attention (SelfGCN), which consists of a mixing features across self-attention and graph convolution (MFSG) module and a temporal-specific spatial self-attention (TSSA) module. The MFSG module models local and global relationships between joints by executing graph convolution and self-attention branches in parallel. Its bi-directional interactive learning strategy utilizes complementary clues in the channel dimensions and the spatial dimensions across both of these branches. The TSSA module uses self-attention to learn the spatial relationships between joints of each frame in a skeleton sequence. It also models the unique spatial features of the single frames. We conduct extensive experiments on three popular benchmark datasets, NTU RGB+D, NTU RGB+D120, and Northwestern-UCLA. The results of the experiment demonstrate that our method achieves or exceeds the record accuracies on all three benchmarks. Our project website is available at https://github.com/SunPengP/SelfGCN.