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1.
Funct Plant Biol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34637699

RESUMO

In vascular plants, bryophytes and algae, the photosynthetic light reaction takes place in the thylakoid membrane where two transmembrane supercomplexes PSII and PSI work together with cytochrome b6f and ATP synthase to harvest the light energy and produce ATP and NADPH. Vascular plant PSI is a 600-kDa protein-pigment supercomplex, the core complex of which is partly surrounded by peripheral light-harvesting complex I (LHCI) that captures sunlight and transfers the excitation energy to the core to be used for charge separation. PSI is unique mainly in absorption of longer-wavelengths than PSII, fast excitation energy transfer including uphill energy transfer, and an extremely high quantum efficiency. From the early 1980s, a lot of effort has been dedicated to structural and functional studies of PSI-LHCI, leading to the current understanding of how more than 200 cofactors are kept at the correct distance and geometry to facilitate fast energy transfer in this supercomplex at an atomic level. In this review, we review the history of studies on vascular plant PSI-LHCI, summarise the present research progress on its structure, and present some new and further questions to be answered in future studies.

2.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472332

RESUMO

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

3.
Photodiagnosis Photodyn Ther ; 36: 102547, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34562647

RESUMO

BACKGROUND: Nucleic acids used as drug delivery systems (DDS) have gained attention because of their biosafety and effortless synthesis. G-quadruplex (G4) structured aptamer such as AS1411 was frequently employed to deliver photosensitizers or chemotherapeutic agents while other aptamers were seldomly reported in this field. METHODS: Herein, a chemical anticancer drug daunomycin (DNM), and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were physically assembled with a novel DNA structure composed of an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-rich DNA fragment (gc-34). Spectral and molecular mimicking methods were employed to research the drug loading/releasing process. The in vitro cytotoxicity was studied by MTT, ROS, cell cycle, and cell apoptotic assays and the in vivo anticancer efficiency was evaluated by the inhibitive effect on the cancerous growth of MCF-7 tumor-bearing nude mice. RESULTS: The G4-structured VEGF aptamer delivered TMPyP successfully for the first time. The designed DDS displayed sensitive VEGF/pH controlled drug release. The co-delivery of DNM and TMPyP exhibited high ROS production, significant cell cycle arresting and evident cell apoptosis, and displayed superior cytotoxicity against tumor cells compared with individual agents in vitro. In vivo studies showed that the dual-drug loaded system can greatly inhibit tumor growth with chemotherapeutic/photodynamic synergistic effects. CONCLUSION: The co-delivery of DNM and TMPyP with aptamer/C-rich DNA successfully integrates the functions of VEGF/pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system, and may have great potential in cancer treatment.

4.
Cell Death Dis ; 12(10): 878, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34564701

RESUMO

The poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. The long noncoding RNA PVT1 (lncRNA PVT1) has been shown to interact with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), promoting gemcitabine resistance in pancreatic cancer. In this study, we found histone acetyltransferase 1 (HAT1) enhanced the tolerance of pancreatic cancer cells to gemcitabine and HAT1-mediated resistance mechanisms were regulated by PVT1 and EZH2. Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance, while silencing HAT1 restored gemcitabine sensitivity. Moreover, HAT1 depletion caused a notable increase of gemcitabine sensitivity in gemcitabine-resistant pancreatic cancer cell lines. Further research found that HAT1 increased PVT1 expression to induce gemcitabine resistance, which enhanced the binding of bromodomain containing 4 (BRD4) to the PVT1 promoter, thereby promoting PVT1 transcription. Besides, HAT1 prevented EZH2 degradation by interfering with ubiquitin protein ligase E3 component n-recognin 4 (UBR4) binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability to elevate the level of EZH2 protein, which also promoted HAT1-mediated gemcitabine resistance. These results suggested that HAT1 induced gemcitabine resistance of pancreatic cancer cells through regulating PVT1/EZH2 complex. Given this, Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to block HAT1 expression and improve the antitumor effect of gemcitabine. The results showed that CS-TPP-siHAT1 nanoparticles augmented the antitumor effects of gemcitabine in vitro and in vivo. In conclusion, HAT1-targeted therapy can improve observably gemcitabine sensitivity of pancreatic cancer cells. HAT1 is a promising therapeutic target for pancreatic cancer.

5.
Am J Med Sci ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547284

RESUMO

BACKGROUND: Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. METHOD: A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore relationship between CS and thyroid hormones. RESULTS: Patients who developed CS (n=103) had lower FT3 and higher FT4 on admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 (<2.25 pg/ml) or higher FT4 (>1.25 ng/dl) was correlated with higher prevalence of CS. Over 2.5 years' follow-up, patients (n=294) with low FT3 (<2.85 pg/ml) and high FT4 (>=0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend <0.0001). CONCLUSIONS: Both FT3 and FT4 are independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in a long-term follow-up.

6.
J Fluoresc ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495469

RESUMO

Although cyanogen ion (CN-) plays important role in industry which also bring acute environmental pollution. More serious, trace CN- enters the human body can cause serious consequences and even death. Therefore, it is of great significance to detect trace CN- with high sensitivity. Herein, a novel aggregation-induced emission (AIE) probe C-BH was synthesized based on coumarin matrix. Probe C-BH showed high selectivity and sensitivity toward CN- by dual channel response due to the excited state intramolecular proton transfer (ESIPT). The low detection limit was calculated to be 0.05 µM. Moreover, probe C-BH was successfully used for imaging CN- in living cells and zebrafish due to its low toxicity and excellent optical properties.

7.
Biomolecules ; 11(8)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34439811

RESUMO

Verticillium wilt, primarily induced by the soil-borne fungus Verticillium dahliae, is a serious threat to cotton fiber production. There are a large number of really interesting new gene (RING) domain-containing E3 ubiquitin ligases in Arabidopsis, of which three (At2g39720 (AtRHC2A), At3g46620 (AtRDUF1), and At5g59550 (AtRDUF2)) have a domain of unknown function (DUF) 1117 domain in their C-terminal regions. This study aimed to detect and characterize the RDUF members in cotton, to gain an insight into their roles in cotton's adaptation to environmental stressors. In this study, a total of 6, 7, 14, and 14 RDUF (RING-DUF1117) genes were detected in Gossypium arboretum, G. raimondii, G. hirsutum, and G. barbadense, respectively. These RDUF genes were classified into three groups. The genes in each group were highly conserved based on gene structure and domain analysis. Gene duplication analysis revealed that segmental duplication occurred during cotton evolution. Expression analysis revealed that the GhRDUF genes were widely expressed during cotton growth and under abiotic stresses. Many cis-elements related to hormone response and environment stressors were identified in GhRDUF promoters. The predicted target miRNAs and transcription factors implied that GhRDUFs might be regulated by gra-miR482c, as well as by transcription factors, including MYB, C2H2, and Dof. The GhRDUF genes responded to cold, drought, and salt stress and were sensitive to jasmonic acid, salicylic acid, and ethylene signals. Meanwhile, GhRDUF4D expression levels were enhanced after V. dahliae infection. Subsequently, GhRDUF4D was verified by overexpression in Arabidopsis and virus-induced gene silencing treatment in upland cotton. We observed that V. dahliae resistance was significantly enhanced in transgenic Arabidopsis, and weakened in GhRDUF4D silenced plants. This study conducted a comprehensive analysis of the RDUF genes in Gossypium, hereby providing basic information for further functional studies.


Assuntos
Proteínas de Arabidopsis/genética , Resistência à Doença/genética , Gossypium/genética , Doenças das Plantas/genética , Imunidade Vegetal/genética , Ubiquitina-Proteína Ligases/genética , Adaptação Fisiológica/genética , Adaptação Fisiológica/imunologia , Arabidopsis/classificação , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/microbiologia , Proteínas de Arabidopsis/metabolismo , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/patogenicidade , Sequência de Bases , Dedos de Zinco CYS2-HIS2/genética , Dedos de Zinco CYS2-HIS2/imunologia , Sequência Conservada , Regulação da Expressão Gênica de Plantas , Gossypium/classificação , Gossypium/imunologia , Gossypium/microbiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , MicroRNAs/genética , MicroRNAs/imunologia , Família Multigênica , Filogenia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estresse Fisiológico , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Ubiquitina-Proteína Ligases/metabolismo
8.
Int J Biol Macromol ; 189: 516-527, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34450147

RESUMO

Rapid endothelialization and regulation of smooth muscle cell proliferation are crucial for small-diameter vascular grafts to address poor compliance, thromboembolism, and intimal hyperplasia, and achieve revascularization. As a gaseous signaling molecule, nitric oxide (NO) regulates cardiovascular homeostasis, inhibits blood clotting and intimal hyperplasia, and promotes the growth of endothelial cells. Due to the instability and burst release of small molecular NO donors, a novel biomacromolecular donor has generated increasing interest. In the study, a low toxic NO donor of S-nitrosated keratin (KSNO) was first synthesized and then coelectrospun with poly(ε-caprolactone) to afford NO-releasing small-diameter vascular graft. PCL/KSNO graft was capable to generate NO under the catalysis of ascorbic acid (Asc), so the graft selectively elevated adhesion and growth of human umbilical vein endothelial cells (HUVECs), while inhibited the proliferation of human aortic smooth muscle cells (HASMCs) in the presence of Asc. In addition, the graft displayed significant antibacterial properties and good blood compatibility. Animal experiments showed that the biocomposite graft could inhibit thrombus formation and preserve normal blood flow via single rabbit carotid artery replacement for 1 month. More importantly, a complete endothelium was observed on the lumen surface. Taken together, PCL/KSNO small-diameter vascular graft has potential applications in vascular tissue engineering with rapid endothelialization and vascular remolding.

9.
Front Public Health ; 9: 685315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395364

RESUMO

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to public health in Southeast Asia, a tropical region with limited resources. This study aimed to investigate the evolutionary dynamics and spatiotemporal patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the region. Materials and Methods: A total of 1491 complete SARS-CoV-2 genome sequences from 10 Southeast Asian countries were downloaded from the Global Initiative on Sharing Avian Influenza Data (GISAID) database on November 17, 2020. The evolutionary relationships were assessed using maximum likelihood (ML) and time-scaled Bayesian phylogenetic analyses, and the phylogenetic clustering was tested using principal component analysis (PCA). The spatial patterns of SARS-CoV-2 spread within Southeast Asia were inferred using the Bayesian stochastic search variable selection (BSSVS) model. The effective population size (Ne) trajectory was inferred using the Bayesian Skygrid model. Results: Four major clades (including one potentially endemic) were identified based on the maximum clade credibility (MCC) tree. Similar clustering was yielded by PCA; the first three PCs explained 46.9% of the total genomic variations among the samples. The time to the most recent common ancestor (tMRCA) and the evolutionary rate of SARS-CoV-2 circulating in Southeast Asia were estimated to be November 28, 2019 (September 7, 2019 to January 4, 2020) and 1.446 × 10-3 (1.292 × 10-3 to 1.613 × 10-3) substitutions per site per year, respectively. Singapore and Thailand were the two most probable root positions, with posterior probabilities of 0.549 and 0.413, respectively. There were high-support transmission links (Bayes factors exceeding 1,000) in Singapore, Malaysia, and Indonesia; Malaysia involved the highest number (7) of inferred transmission links within the region. A twice-accelerated viral population expansion, followed by a temporary setback, was inferred during the early stages of the pandemic in Southeast Asia. Conclusions: With available genomic data, we illustrate the phylogeography and phylodynamics of SARS-CoV-2 circulating in Southeast Asia. Continuous genomic surveillance and enhanced strategic collaboration should be listed as priorities to curb the pandemic, especially for regional communities dominated by developing countries.


Assuntos
COVID-19 , SARS-CoV-2 , Ásia Sudeste/epidemiologia , Teorema de Bayes , Genoma Viral/genética , Humanos , Filogenia
10.
Genes (Basel) ; 12(7)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34356061

RESUMO

Cottonseed oil is rich in unsaturated fatty acids (UFAs) and serves as an edible oil in human nutrition. Reports suggest that acyl-coenzyme A: diacylglycerol acyltransferases (DGAT) and wax ester synthase/DGAT (WSD1) genes encode a key group of enzymes that catalyze the final step for triacylglycerol biosynthesis and enable an important rate-limiting process. However, their roles in oil biosynthesis and the fatty acid profile of cotton seed are poorly understood. Therefore, the aim of this study was to identify and characterize DGAT and WSD1 genes in cotton plants and examine their roles in oil biosynthesis, the fatty acid profile of cotton seeds, and abiotic stress responses. In this study, 36 GhDGAT and GhWSD1 genes were identified in upland cotton (G. hirsutum) and found to be clustered into four groups: GhDGAT1, GhDGAT2, GhDGAT3, and GhWSD1. Gene structure and domain analyses showed that the GhDGAT and GhWSD1 genes in each group are highly conserved. Gene synteny analysis indicated that segmental and tandem duplication events occurred frequently during cotton evolution. Expression analysis revealed that GhDGAT and GhWSD1 genes function widely in cotton development and stress responses; moreover, several environmental stress and hormone response-related cis-elements were detected in the GhDGAT and GhWSD1 promoter regions. The predicted target transcription factors and miRNAs imply an extensive role of GhDGAT and GhWSD1 genes in stress responses. Increases in GhDGAT3 gene expression with increases in cottonseed oil accumulation were observed. Transformation study results showed that there was an increase in C18:1 content and a decrease in C18:2 and C18:3 contents in seeds of Arabidopsis transgenic plants overexpressing GhDGAT3D compared with that of control plants. Overall, these findings contributed to the understanding of the functions of GhDGAT and GhWSD1 genes in upland cotton, providing basic information for further research.

11.
Cells ; 10(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34440912

RESUMO

During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. T central memory (TCM), T effector memory (TEM), and long-lived effector (LLE) cells are circulating memory populations with distinct plasticity, migration patterns, and effector functions. Tissue-resident memory (TRM) cells permanently reside in the frontline sites of pathogen entry and provide tissue-specific protection upon reinfection. Here, using single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq, we examined the different and shared transcriptomes and regulators of TRM cells with other circulating memory populations. Furthermore, we identified heterogeneity within the TRM pool from small intestine and novel transcriptional regulators that may control the phenotypic and functional heterogeneity of TRM cells during acute infection. Our findings provide a resource for future studies to identify novel pathways for enhancing vaccination and immunotherapeutic approaches.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34382925

RESUMO

A novel Gram-stain-negative strain, WQ 117T, isolated from the faeces of Rhinopithecus bieti collected at Yunnan Snub-nosed Monkey National Park, Yunnan province, PR China, was subjected to a polyphasic taxonomic study. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate represented a member of the genus Faecalibacter, sharing 97.64 % sequence similarity with the type strain Faecalibacter macacae YIM 102668T. The G+C content of the genomic DNA of WQ117T was 30.5 mol%. The predominant isoprenoid quinone was MK-6. The major cellular fatty acids was iso-C15 : 0. The whole genome average nucleotide identity (gANI) values and the digital DNA-DNA hybridization values between WQ 117T and YIM 102668T were 79.66 % and 22.20 %, respectively. Growth occurred at 0-50 °C (optimally at 28-35 °C), pH 7.0-9.0 (optimally at pH 8.0) and with 0-2 % (w/v) NaCl (optimally without NaCl). On the basis of the taxonomic evidence, a novel species, Faecalibacter rhinopitheci sp. nov., is proposed. The type strain is WQ 117T (=KCTC 82394T=CCTCC AA 2020027T).


Assuntos
Bacteroidetes/classificação , Filogenia , Presbytini , Animais , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Hibridização de Ácido Nucleico , Presbytini/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
14.
Zhongguo Gu Shang ; 34(8): 717-24, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34423614

RESUMO

OBJECTIVE: To observe the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and nerve function in patients with spinal tuberculosis before and after surgery, explore the timing of surgical intervention, and evaluate its influence on surgical safety. METHODS: A retrospective analysis was conducted on 387 patients with spinal tuberculosis who received surgical treatment from March 2012 to March 2017, including 278 males and 109 females, aged 12 to 86 years old with an average of (49.9±19.1) years. There were 64 cases of cervical tuberculosis, 86 cases of thoracic tuberculosis, 76 cases of thoracolumbar tuberculosis and 161 cases of lumbar tuberculosis. There were 297 patients with single segmental involvementand 90 patients with multiple segmental involvement. Among them, 62 cases presented neurological damage, and preoperative spinal cord neurological function depended on ASIA grade, 5 cases of grade A, 8 cases of grade B, 39 cases of grade C, and 10 cases of grade D. According to the duration of preoperative antituberculosis treatment, the patients were divided into group A (256 cases, receiving conventional quadruple antituberculosis treatment for 2-4 weeks before surgery) and group B (131 cases, receiving conventional quadruple antituberculosis treatment for more than 4 weeks before surgery). The two groups were compared in terms of gender, age, preoperative complicated pulmonary tuberculosis, lesion site, lesion scope, surgical approach, drug resistance and other general clinical characteristics. ESR, CRP, visual analogue scale(VAS), Oswestry Disability Index (ODI), Frankel grade and postoperative complications were observed. RESULTS: All 387 patients were followed up for 12 to 36 (18.3±4.5) months. There were no significant differences in gender, age, preoperative pulmonary tuberculosis, lesion site, lesion range, surgical approach, preoperative drug resistance and other characteristics between two groups. A total of 32 patients in two groups did not heal after surgery, with an incidence rate of 8.27%. The VAS and spinal cord dysfunction index of the two groups were significantly improved after surgery (P<0.05), but there was no significant difference between two groups at the same time point (P>0.05) . From 1 to 14 days after operation, the neurological function began to gradually recover, and the neurological function grade was increased by 1 to 3 grades. From 3 months after operation to the final follow up, 52 cases recovered completely, 8 cases partially recovered, and 2 cases did not improve. There was no significant difference in ESR and CRP between two groups before admission, 1 month after surgery, and final follow-up (P>0.05). CONCLUSION: After 2-4 weeks of anti tuberculosis treatment before operation, patients with spinal tuberculosis could be operated upon with ESR and CRP in a descending or stable period. In principle, patients with spinal tuberculosis and paraplegia should be treated as soon as possible after active preoperative management of the complication without emergency surgery.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas , Tuberculose da Coluna Vertebral/cirurgia , Adulto Jovem
15.
Front Immunol ; 12: 716075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394120

RESUMO

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.


Assuntos
Doenças Assintomáticas , COVID-19/imunologia , Portador Sadio/imunologia , Leucócitos Mononucleares/imunologia , SARS-CoV-2/imunologia , Transcriptoma/genética , Adulto , Portador Sadio/virologia , Ativação do Complemento/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/imunologia , Influenza Humana/complicações , Interferons/sangue , Interferons/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transcriptoma/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
16.
Chin J Traumatol ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34419336

RESUMO

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, the 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.

17.
Nat Immunol ; 22(8): 996-1007, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34282329

RESUMO

During chronic viral infection, CD8+ T cells develop into three major phenotypically and functionally distinct subsets: Ly108+TCF-1+ progenitors, Ly108-CX3CR1- terminally exhausted cells and the recently identified CX3CR1+ cytotoxic effector cells. Nevertheless, how CX3CR1+ effector cell differentiation is transcriptionally and epigenetically regulated remains elusive. Here, we identify distinct gene regulatory networks and epigenetic landscapes underpinning the formation of these subsets. Notably, our data demonstrate that CX3CR1+ effector cells bear a striking similarity to short-lived effector cells during acute infection. Genetic deletion of Tbx21 significantly diminished formation of the CX3CR1+ subset. Importantly, we further identify a previously unappreciated role for the transcription factor BATF in maintaining a permissive chromatin structure that allows the transition from TCF-1+ progenitors to CX3CR1+ effector cells. BATF directly bound to regulatory regions near Tbx21 and Klf2, modulating their enhancer accessibility to facilitate the transition. These mechanistic insights can potentially be harnessed to overcome T cell exhaustion during chronic infection and cancer.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Coriomeningite Linfocítica/imunologia , Proteínas com Domínio T/genética , Subpopulações de Linfócitos T/citologia , Animais , Antígenos Ly/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular , Feminino , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Vírus da Coriomeningite Linfocítica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subpopulações de Linfócitos T/imunologia
18.
Cardiovasc Intervent Radiol ; 44(10): 1597-1608, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34240232

RESUMO

OBJECTIVES: Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. RESULTS: A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. CONCLUSIONS: The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

19.
Nat Plants ; 7(8): 1132-1142, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34226692

RESUMO

Photosystem II (PSII) is a multisubunit pigment-protein complex and catalyses light-induced water oxidation, leading to the conversion of light energy into chemical energy and the release of dioxygen. We analysed the structures of two Psb28-bound PSII intermediates, Psb28-RC47 and Psb28-PSII, purified from a psbV-deletion strain of the thermophilic cyanobacterium Thermosynechococcus vulcanus, using cryo-electron microscopy. Both Psb28-RC47 and Psb28-PSII bind one Psb28, one Tsl0063 and an unknown subunit. Psb28 is located at the cytoplasmic surface of PSII and interacts with D1, D2 and CP47, whereas Tsl0063 is a transmembrane subunit and binds at the side of CP47/PsbH. Substantial structural perturbations are observed at the acceptor side, which result in conformational changes of the quinone (QB) and non-haem iron binding sites and thus may protect PSII from photodamage during assembly. These results provide a solid structural basis for understanding the assembly process of native PSII.


Assuntos
Proteínas de Bactérias/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Precursores de Proteínas/metabolismo , Thermosynechococcus/genética , Thermosynechococcus/metabolismo , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Complexos de Proteínas Captadores de Luz/genética , Estrutura Molecular , Complexo de Proteína do Fotossistema II/genética
20.
Harmful Algae ; 105: 102055, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34303516

RESUMO

Blooms of Margalefidinium (previously Cochlodinium) polykrikoides occur almost annually in summer in the lower Chesapeake Bay and its tributaries (e.g., the James and York Rivers). The Lafayette River, a sub-tributary of the lower James River, has been recognized as an initiation location for blooms in this region. The timing of bloom initiation varies interannually, ranging from late June to early August. To fully understand critical environmental factors controlling bloom initiation and interactions between physical and biological processes, a numerical module simulating M. polykrikoides blooms was developed with a focus on the bloom initiation. The module also includes life cycle and behavioral strategies such as mixotrophy, vertical migration, cyst dynamics and grazing suppression. Parameterizations for these behaviors were assigned based on published laboratory culture experiments. The module was coupled with a 3D physical-biogeochemical model for the James River that examined the contribution of each environmental factor and behavioral strategy to bloom initiation and development. Model simulation results highlight the importance of mixotrophy in maintaining high growth rates for M. polykrikoides in this region. Model results suggest that while many factors contribute to the initiation process, temperature, physical transport processes, and cyst germination are the three dominant factors controlling the interannual variability in the timing of bloom initiation.


Assuntos
Dinoflagelados , Proliferação Nociva de Algas , Estuários , Rios , Temperatura
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