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Analysis of bacterial carbohydrate-active enzymes (CAZymes) contributes significantly to comprehending the response exhibited by coral symbionts to the external environment. This study explored the impact of bleaching on the bacteria and their CAZymes in coral Favites sp. through metagenomic sequencing. Notably, principal coordinates analysis (PCoA) unveiles substantial difference in bacterial communities between bleached and unbleached corals. Proteobacteria, Actinobacteria, Acidobacteria, Bacteroidota, and Chloroflexi, exhibit noteworthy alterations during coral bleaching. CAZymes profiles in bleached coral disclosed a significant increase in Glycosyltransferases (GTs) abundance, suggesting an intensified biosynthesis of polysaccharides. Conversely, there is a marked reduction in other CAZymes abundance in bleached coral. Proteobacteria, Bacteroidota, Chlorobi, and Planctomycetota exhibit greater contributions to CAZymes in bleached corals, with Rhodobacterales, Cytophagales, Burkholderiales, Caulobacterales, and Hyphomicrobiales being the main contributors. While Acidobacteria, Actinobacteria, and Chloroflexi demonstrate higher contributions to CAZymes in unbleached corals. The changes in bacteria and their CAZymes reflect the ecological adaptability of coral holobionts when facing environmental stress. The alterations in CAZymes composition caused by bleaching events may have profound impacts on coral nutrient absorption and ecosystem stability. Therefore, understanding the dynamic changes in CAZymes is crucial for assessing the health and recovery potential of coral ecosystems.
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Medical immunology is an important link between basic experiments and clinical applications, and it is also the intersection of many cutting-edge disciplines. At present, there are still limitations in immunology teaching such as single teaching methods and insufficient scientific research training for students. Department of Immunology has implemented practice and exploration of "scientific research back-feeding teaching" in medical immunology course. By incorporating scientific research into teaching activities, the team has carried out teaching practice through scientific research platforms, enriched teaching content with scientific research progress, conducted scientific research activities to stimulate students' interest, which not only increase students' inner drive, improves teaching efficiency, and leads to a "win-win" situation of teaching and scientific research, but also contributes to training medical innovative talents who can shoulder the heavy responsibility of the country.
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Alergia e Inmunología , Enseñanza , Humanos , Alergia e Inmunología/educación , Educación Médica/métodos , Investigación Biomédica/educaciónRESUMEN
Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency commonly occurs in critically ill patients, but supplementary iron therapy is not considered during the acute phase of critical illness since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful and has potential adverse outcomes such as cognitive dysfunction, fatigue, and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency quickly and efficiently. This article reviews current knowledge about iron-related biomarkers in critical illness with a focus on patients with sepsis, and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of those patients.
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Enfermedad Crítica , Hierro , Sepsis , Humanos , Sepsis/metabolismo , Hierro/metabolismo , Biomarcadores/metabolismo , Animales , Deficiencias de HierroRESUMEN
Contaminant accumulation in organisms can be influenced by both biological traits and environmental conditions. However, delineating the main factors affecting contaminant burdens in organisms remains challenging. Here, we conducted an initial investigation into the impact of diet and habitat on the accumulation of short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in Indo-Pacific humpback dolphins (2003-2020, n = 128) from the Pearl River Estuary (PRE), a highly polluted estuary in China. The detected levels of SCCPs (5897 ± 3480 ng g-1 lw) and MCCPs (13,960 ± 8285 ng g-1 lw) in blubber samples of humpback dolphin are the highest among recorded values marine mammals. Both SCCPs and MCCPs exhibited biomagnification factor values exceeding 1, suggesting their biomagnification potential within the dolphins and their diet. Quantitative diet analysis using the dolphin fatty acid signatures revealed that humpback dolphins inhabiting the western PRE consumed a larger proportion of carnivorous fish than those from the eastern PRE. However, spatial analysis showed that humpback dolphins in the western PRE contained lower SCCP/MCCP concentrations than those from the eastern PRE. Based on these findings we suggest that, compared to diet differences, spatial variations of SCCPs/MCCPs in humpback dolphins may be predominantly influenced by their space-use strategies, as the eastern PRE is closer to the pollutant discharge source and transfer routes.
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Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator DIBI in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI is a polymer with a polyvinylpyrrolidone backbone containing nine 3-hydroxy-1-(methacrylamidoethyl)-2-methyl-4(1H) pyridinone (MAHMP) residues per molecule and was given by intraperitoneal injection either as a single dose (80 mg/kg) immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1ß, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24 h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.
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Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.
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Linfocitos T CD8-positivos , Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Humanos , Femenino , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Receptores CXCR5/metabolismo , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Adulto , Persona de Mediana Edad , Linfocitos B/inmunología , Linfocitos B/metabolismo , Inmunoglobulinas/metabolismo , Inmunoglobulinas/inmunología , Enfermedades Desmielinizantes/inmunología , Enfermedades Desmielinizantes/patologíaRESUMEN
Compared to traditional continuous performance tasks, virtual reality-based continuous performance tests (VR-CPT) offer higher ecological validity. While previous studies have primarily focused on behavioral outcomes in VR-CPT and incorporated various distractors to enhance ecological realism, little attention has been paid to the effects of distractors on EEG. Therefore, our study aimed to investigate the influence of distractors on EEG during VR-CPT. We studied visual distractors and auditory distractors separately, recruiting 68 subjects (M =20.82, SD =1.72) and asking each to complete four tasks. These tasks were categorized into four groups according to the presence or absence of visual and auditory distractors. We conducted paired t-tests on the mean relative power of the five electrodes in the ROI region across different frequency bands. Significant differences were found in theta waves between Group 3 (M =2.49, SD =2.02) and Group 4 (M =2.68, SD =2.39) (p < 0.05); in alpha waves between Group 3 (M =2.08, SD =3.73) and Group 4 (M =3.03, SD =4.60) (p < 0.001); and in beta waves between Group 1 (M = -4.44 , SD =2.29) and Group 2 (M = -5.03 , SD =2.48) (p < 0.001), as well as between Group 3 (M = -4.48 , SD =2.03) and Group 4 (M = -4.67 , SD =2.23) (p < 0.05). The incorporation of distractors in VR-CPT modulates EEG signals across different frequency bands, with visual distractors attenuating theta band activity, auditory distractors enhancing alpha band activity, and both types of distractors reducing beta oscillations following target stimuli. This insight holds significant promise for the rehabilitation of children and adolescents with attention deficits.
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Atención , Electroencefalografía , Realidad Virtual , Humanos , Masculino , Femenino , Electroencefalografía/métodos , Adulto Joven , Atención/fisiología , Adulto , Percepción Visual/fisiología , Ritmo Teta/fisiología , Estimulación Acústica/métodos , Ritmo alfa/fisiología , Estimulación Luminosa , Percepción Auditiva/fisiología , Desempeño Psicomotor/fisiologíaRESUMEN
AIMS: The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on oral microbial colonization in infants fed by gastric tube at different time points. METHODS: Infants (n = 116) with birth weight <1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The control group (n = 51) accepted oropharyngeal normal saline administration. The experimental group (n = 53) accepted oropharyngeal mother's milk administration before fed by gastric tube once every 3 h over 21 days after birth. We analyzed the oral microbiota at initiation and 7 and 14 and 21 days later using 16S DNA amplicon sequencing. RESULTS: There were no difference in oral microbial diversity between the two groups at any time point, but diversity decreased significantly over time in both groups. On the first day of life, the oral microbiota of the infant in the experimental and control groups consisted mainly of Firmicutes (7.75%, 6.18%) and Proteobacteria (68.65%, 68.69%), respectively. As time increases to 21 days after birth, Firmicutes (77.67%, 77.66%) had replaced Proteobacteria (68.65%, 68.69%) as the predominant phylum. DISCUSSION: From birth to 21 days after birth, oropharyngeal mother's milk administration did not change the diversity and structural composition of the oral microbiota. The oral microbial diversity of infants declined significantly over time. Firmicutes had replaced Proteobacteria as the predominant phylum.
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Leche Humana , Madres , Femenino , Humanos , Recién Nacido , Recién Nacido de muy Bajo PesoRESUMEN
Enhanced recovery after surgery (ERAS) is a multimodal perioperative management concept, but there is no article to comprehensively review the collaboration and impact of countries, institutions, authors, journals, references, and keywords on ERAS from a bibliometric perspective. This study assessed the evolution of clustering of knowledge structures and identified hot trends and emerging topics. Articles and reviews related to ERAS were retrieved through subject search from the Web of Science Core Collection. We used the following strategy: "TS = Enhanced recovery after surgery" OR "Enhanced Postsurgical Recovery" OR "Postsurgical Recoveries, Enhanced" OR "Postsurgical Recovery, Enhanced" OR "Recovery, Enhanced Postsurgical" OR "Fast track surgery" OR "improve surgical outcome". Bibliometric analyses were conducted on Excel 365, CiteSpace, VOSviewer, and Bibliometrics (R-Tool of R-Studio). Totally 3242 articles and reviews from 1997 to 2022 were included. These publications were mainly from 684 journals in 78 countries, led by the United States and China. Kehlet H published the most papers and had the largest number of co-citations. Analysis of the journals with the most outputs showed that most journals mainly cover Surgery and Oncology. The hottest keyword is "enhanced recovery after surgery". Later appearing topics and keywords indicate that the hotspots and future research trends include ERAS protocols for other types of surgery and improving perioperative status, including "bariatric surgery", "thoracic surgery", and "prehabilitation". This study reviewed the research on ERAS using bibliometric and visualization methods, which can help scholars better understand the dynamic evolution of ERAS and provide directions for future research.
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Bibliometría , Recuperación Mejorada Después de la Cirugía , HumanosRESUMEN
As long-lived apex predators, marine mammal adults often accumulate alarmingly levels of environmental contaminants. Nevertheless, the accumulation and risks of these contaminants in the critical calf stage of marine mammals remain largely unknown. Here, we investigated the exposure status and health risks of 74 organohalogen contaminants (OHCs) in Indo-Pacific humpback dolphin calves (Sousa chinensis) collected from the Pearl River Estuary (PRE), China, during 2005-2019. Our findings revealed moderate levels of polychlorinated biphenyls (PCBs), medium-high levels of dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs), and the highest levels of polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs) compared to those reported for cetaceans elsewhere. Traditional OHCs like DDTs, PCBs, and PBDEs did not exhibit significant decreasing trends in the dolphin calves despite global restrictions on these compounds, and AHFRs as emerging OHCs showed an increasing trend over the study period. Risk quotients of DDTs, HCHs, PBDEs, and PCBs in most of the dolphin samples were > 1, indicating that humpback dolphin calves may have suffered long-term threats from OHC exposure. The significant correlation observed between the traditional OHC levels and the stranding death number of the dolphin calves suggests these OHCs may impact the survival of this endangered species.
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Delfines , Bifenilos Policlorados , Animales , Bifenilos Policlorados/análisis , Éteres Difenilos Halogenados/toxicidad , Monitoreo del Ambiente , Hexaclorociclohexano , EcosistemaRESUMEN
Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.
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Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/genética , Metabolismo de los Lípidos/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
Despite the increasing health risks shown by the continuous detection of organophosphate esters (OPEs) in biota in recent years, information on the occurrence and potential risks of OPEs in marine mammals remains limited. This study conducted the first investigation into the body burdens and potential risks of 10 traditional OPEs (tOPEs) and five emerging OPEs (eOPEs) in 10 cetacean species (n = 84) from the northern South China Sea (NSCS) during 2005-2021. All OPEs, except for 2-ethylhexyl diphenyl phosphate (EHDPHP), were detected in these cetaceans, indicating their widespread occurrence in the NSCS. Although the levels of the ∑10tOPEs in humpback dolphins remained stable from 2005 to 2021, the concentrations of the ∑5eOPEs showed a significant increase, suggesting a growing demand for these new-generation OPEs in South China. Dolphins in proximity to urban regions generally exhibited higher OPE concentrations than those from rural areas, mirroring the environmental trends of OPEs occurring in this area. All OPE congeners, except for EHDPHP, in humpback dolphins exhibited a maternal transfer ratio >1, indicating that the dolphin placenta may not be an efficient barrier for OPEs. The observed significant correlations between levels of OPEs and hormones (triiodothyronine, thyroxine, and testosterone) in humpback dolphins indicated that OPE exposures might have endocrine disruption effects on the dolphin population.
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Delfines , Retardadores de Llama , Animales , Monitoreo del Ambiente , Bioacumulación , Ésteres , China , Organofosfatos , Fosfatos , Retardadores de Llama/análisisRESUMEN
Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.
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Cardiomiopatías Diabéticas , Miocitos Cardíacos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Cardiomiopatías Diabéticas/inducido químicamente , Cardiomiopatías Diabéticas/metabolismo , Vía de Señalización Hippo , Ratones Endogámicos C57BL , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/metabolismo , Factores de Diferenciación de Crecimiento/farmacología , Glucosa/farmacología , Glucosa/metabolismo , Apoptosis/genéticaRESUMEN
Plastic additives, such as organophosphate esters (OPEs) and phthalate esters (PAEs), are raising public concerns due to their widespread presence and potential health risks. Nonetheless, the occurrences and potential health risks of these additives in marine mammals remain limited. Here, we first investigated the accumulation patterns and potential risks of OPEs and metabolites of PAEs (mPAEs) in Indo-Pacific finless porpoises inhabiting the northern South China Sea (NSCS) during 2007-2020. The average hepatic concentrations of ∑15OPEs and ∑16mPAEs in the NSCS finless porpoises were 53.9 ± 40.7 and 98.6 ± 54.8 ng/g ww, respectively. The accumulation of mPAEs and OPEs in the finless porpoises is associated with the chemical structures of the compounds. ∑5halogenated-OPEs were the most dominant category (62.6%) of ∑15OPEs, followed by ∑6aryl-OPEs (25.9%) and ∑6nonhalogenated alkyl-OPEs (11.5%). The accumulation of mPAEs displayed a declining trend with increasing alkyl side chain length (C0-C10). Although the hepatic burden of mPAEs in finless porpoises was sex-independent, some OPEs, including TDCIPP, TBOEP, TCIPP, TCrP, TPHP, and TDBPP, exhibited significantly higher concentrations in adult males than in adult females. TDBPP, as a new-generation OPE, exhibited a gradual increase during the study period, suggesting that TDBPP should be prioritized for monitoring in the coastal regions of South China. The estimated hazard quotient indicated that almost all mPAEs and OPEs pose no hazard to finless porpoises, with only DEHP presenting potential health risks to both adult and juvenile finless porpoises.
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Marsopas , Masculino , Animales , Femenino , Marsopas/metabolismo , Monitoreo del Ambiente , China , Organofosfatos/análisis , Océanos y Mares , Ésteres/análisisRESUMEN
Unsaturated fatty acids (UFAs) are known to play a vital role in regulating stress resistance and metabolism in corals. Nevertheless, a comprehensive understanding of the microbial and functional composition of the UFA synthesis pathway (UFASP) remains lacking. This study employed metagenome and metabolome to investigate the microbial community, function, and metabolic response of UFASP in reef-building corals inhabiting the Nansha Islands. Our findings revealed significantly higher diversity for the UFASP microbe in bleached corals compared to unbleached corals. Furthermore, principal coordinates analysis (PCoA) and taxonomy assessments exhibited notable distinctions in the microbe between the two coral states. Notably, the dominant microorganisms involved in UFASP were Dinophyceae, Sordariomycetes, Ulvophyceae, and Chlorophyceae. Bleaching resulted in a considerable increase in fungal abundance within coral symbionts. A total of 12 KEGG Orthology (KO) were identified in UFASP, with PCoA analysis indicating significant differences in their abundance between bleached and unbleached corals. UFASP's beta-Oxidation module exhibited reduced abundance in bleached corals. Contribution analysis highlighted the participation of Symbiodiniaceae, Ascomycota, Chlorophyta, Proteobacteria, and Actinobacteria in UFASP. Notably, Symbiodiniaceae and Ascomycota were the major contributors to two UFASP modules, with the latter displaying greater involvement in bleached corals. Furthermore, significant differences in n3 and n6-family metabolites were observed between bleached and unbleached corals. Notably, bleaching induced a reduction in metabolites of Symbiodiniaceae, while an increase in the multiple UFAs abundance was detected in bleached corals. These findings suggest that bleaching-induced alterations coral symbionts composition directly impact the functionality of UFASP, ultimately affecting the corals' capacity to adapt to stress.
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Antozoos , Dinoflagelados , Animales , Antozoos/fisiología , Metagenoma , Bacterias , Dinoflagelados/fisiología , Adaptación Fisiológica , Arrecifes de Coral , SimbiosisRESUMEN
Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called LHX1-DT, which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene. Our findings demonstrated that LHX1-DT is nuclear-localized and transiently elevated expression along with LHX1 during early differentiation of cardiomyocytes. The phenotype was rescued by overexpression of LHX1 into the LHX1-DT-/- hESCs, indicating LHX1 is the downstream of LHX1-DT. Mechanistically, we discovered that LHX1-DT physically interacted with RNA/histone-binding protein PHF6 during mesoderm commitment and efficiently replaced conventional histone H2A with a histone variant H2A.Z at the promoter region of LHX1. In summary, our work uncovers a novel lncRNA, LHX1-DT, which plays a vital role in mediating the exchange of histone variants H2A.Z and H2A at the promoter region of LHX1.
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(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host cells. DNA vaccines for EBOV are in development, but their effectiveness is unclear. The lack of immune characteristics resides in antigenic MHC class II reactivity. (2) Methods: We selected MHC-II molecules from four human leukocyte antigen II (HLA-II) superfamilies with 98% population coverage and eight mouse H2-I alleles. IEDB, NetMHCIIpan, SYFPEITHI, and Rankpep were used to screen MHC-II-restricted epitopes with high affinity for EBOV GP. Further immunogenicity and conservation analyses were performed using VaxiJen and BLASTp, respectively. EpiDock was used to simulate molecular docking. Cluster analysis and binding affinity analysis of EBOV GP epitopes and selected MHC-II molecules were performed using data from NetMHCIIpan. The selective GP epitopes were verified by the enzyme-linked immunospot (ELISpot) assay using splenocytes of BALB/c (H2d), C3H, and C57 mice after DNA vaccine pVAX-GPEBO immunization. Subsequently, BALB/c mice were immunized with Protein-GPEBO, plasmid pVAX-GPEBO, and pVAX-LAMP/GPEBO, which encoded EBOV GP. The dominant epitopes of BALB/c (H-2-I-AdEd genotype) mice were verified by the enzyme-linked immunospot (ELISpot) assay. It is also used to evaluate and explore the advantages of pVAX-LAMP/GPEBO and the reasons behind them. (3) Results: Thirty-one HLA-II-restricted and 68 H2-I-restricted selective epitopes were confirmed to have high affinity, immunogenicity, and conservation. Nineteen selective epitopes have cross-species reactivity with good performance in MHC-II molecular docking. The ELISpot results showed that pVAX-GPEBO could induce a cellular immune response to the synthesized selective peptides. The better immunoprotection of the DNA vaccines pVAX-LAMP/GPEBO coincides with the enhancement of the MHC class II response. (4) Conclusions: Promising MHC-II-restricted candidate epitopes of EBOV GP were identified in humans and mice, which is of great significance for the development and evaluation of Ebola vaccines.
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Acute lung injury (ALI) has been challenging health care systems since before the COVID-19 pandemic due to its morbidity, mortality, and length of hospital stay. In view of the complex pathogenesis of ALI, effective strategies for its prevention and treatment are still lacking. A growing body of evidence suggests that iron dysregulation is a common characteristic in many subtypes of ALI. On the one hand, iron is needed to produce reactive oxygen species (ROS) as part of the immune response to an infection; on the other hand, iron can accelerate the occurrence of ferroptosis and extend host cell damage. Iron chelation represents a novel therapeutic strategy for alleviating lung injury and improving the survival of patients with ALI. This article reviews the current knowledge of iron homeostasis, the role of iron in ALI development, and potential therapeutic targets.
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Food has regularly been proven to be a key source of exposure to environmental pollutants, drawing attention to the dietary exposure risks of contaminants to mammals with significant daily food intake. Here, the levels of six organotin compounds (OTs) in 18 fish (n = 310), three cephalopods (n = 50), and one shrimp (n = 34) from the Lingdingyang (LDY) and west four region (WFR) of the Pearl River Estuary (PRE) and their dietary exposure risks to Indo-Pacific humpback dolphins and humans were first investigated. Total OT levels ranged from 3.84 to 901. 48 ng/g wet weight (ww) in 22 prey species from the LDY, and from 14.37 to 1364.64 ng/g ww in 19 species from the WFR. The LDY marine species generally accumulated higher butyltin levels but lower phentyltin levels than those in the WFR. All species have a phenyltin degradation index <1 and over 60 % of the sampled species have a butyltin degradation index <1, suggesting the PRE marine species might be exposed to the fresh discharge of OTs. A total of nine marine species exceeded the threshold levels of OT intake for adverse health effects on human juveniles by consumption, all 22 marine species posed high dietary risks to the PRE humpback dolphins. Moreover, probabilistic risk assessment using Monte Carlo simulation revealed that the probabilities of RQ values associated with WFR OT exposure higher than 1 were 18.87 % for human adults, 40.55 % for human juveniles, 100 % for both humpback dolphin adults and humpback dolphin juveniles. Our results highlighted the potentially high dietary exposure risks of OTs to marine mammals and residents in the PRE.
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Seafood has long been considered a healthy food choice, but it is also an exposure source of contaminants that may bring potential health risks to humans. Here, 80 organohalogen contaminants (OHCs) and 36 fatty acids (FAs) were analyzed in 22 (n = 211) and 19 fishery species (n = 176) from the eastern- and western Pearl River Estuary (PRE), respectively, for risk-benefit analysis. The average concentrations of total FAs in seafood from the eastern- and western PRE were 26.0 ± 2.14 and 21.3 ± 1.66 mg g-1 wet weight, respectively. Seafood from the eastern PRE exhibited higher levels of OHCs than those from the western PRE, highlighting the spatial heterogeneity of OHC contamination within the PRE. Species occupying higher trophic levels (TLs) typically demonstrated higher levels of OHC accumulation, indicating the biomagnification potential of these contaminants in the PRE ecosystem. Significant negative correlations were observed between TLs and the proportions of monounsaturated fatty acids and polyunsaturated fatty acids, presumably attributed to the ability of fish to synthesize these FAs decreases with increasing TLs. Our benefit-risk quotient (BRQ) analyses revealed that, as far as OHCs are concerned, all seafood species had a BRQ∑OHCs value <1, except for one-spot snapper and daggertooth pike conger, which had BRQ values of 1.03 and 1.14, respectively. The findings indicate that most marine species here analyzed may not pose significant health risks to consumers as a result of OHC exposure. However, considering that many other pollutants and nutrients are not analyzed here, the results of our risk assessments should be treated as preliminary, not final. Future data collection is essential to enhance the comprehensiveness of this type of analysis.