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1.
Anal Methods ; 15(37): 4883-4891, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37712204

RESUMO

Coatings are considered to play a crucial role in solid-phase microextraction (SPME). In this work, a novel coating named ZIF-67/[HOEMIM]BF4 was fabricated through in situ potentiostatic electrodeposition in methanol solutions containing ZIF-67 precursors and 1-(2'-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ([HOEMIM]BF4). Compared with the traditional solvothermal method, this method reduced the synthesis time and enabled ZIF-67 to grow directly on the surface of stainless-steel wire, effectively simplifying the preparation process and improving the coating reproducibility. Owing to the inherent characteristics such as high porosity and high thermal and mechanical stability, and the impressive morphological regulation and extraction function of [HOEMIM]BF4, the developed coating exhibited a prolonged service life and a better extraction capacity for trace polycyclic aromatic hydrocarbons (PAHs) compared to single ZIF-67 and commercial fibers. Under the optimal conditions, the linear range of the ZIF-67/[HOEMIM]BF4-based SPME-GC method was 0.01-500 µg L-1, and the detection limit was 0.27-5.2 ng L-1. When applied in the determination of PAHs in a real water sample, recoveries between 85.6-117.3% were obtained, indicating the potential of ZIF-67/[HOEMIM]BF4 in the high efficiency SPME and GC analysis of PAHs.

2.
Analyst ; 148(17): 4203-4212, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37539587

RESUMO

Extraction and determination of trace hazardous components from complex matrices continue to attract public attention. In this work, magnetic porous carbon (MPC) was prepared for efficient magnetic solid phase extraction (MSPE) of fluoroquinolone (FQ) antibiotics in food and water samples. To prepare the MPC, an Fe-based metal-organic framework (MIL-101(Fe)) was grown on a network of graphene oxide and multi-walled carbon nanotubes through a hydrothermal method, and then a carbonization process under a nitrogen atmosphere was carried out to obtain the MPC with high specific surface area and good magnetism. Four target FQs including ciprofloxacin (CIP), enrofloxacin (ENO), lomefloxacin (LOM) and ofloxacin (OFX) were enriched using the as-prepared MPC and determined by coupled high-performance liquid chromatography. Under the optimal conditions, the established MSPE-HPLC-UV detection method exhibited a linear range of 0.5-800 µg L-1 and detection limits of 0.11-0.18 µg L-1 with relative standard deviations (RSDs) of 0.5-4.8%. When applied in the determination of the above four FQs in real samples such as lake water, milk and pork, good recoveries between 85.2 and 103.7% were obtained, and the RSDs were less than 4.8%. This work indicates that the MPC material can be a good adsorption material and has good application prospects in antibiotics enrichment and/or removal from complex samples.


Assuntos
Estruturas Metalorgânicas , Nanotubos de Carbono , Estruturas Metalorgânicas/química , Porosidade , Fluoroquinolonas/análise , Fluoroquinolonas/química , Antibacterianos/análise , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Adsorção , Água , Fenômenos Magnéticos , Limite de Detecção
3.
Phytother Res ; 37(10): 4722-4739, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37443453

RESUMO

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.


Assuntos
Neoplasias Ovarianas , Trombospondina 1 , Animais , Camundongos , Humanos , Feminino , Carcinoma Epitelial do Ovário , Trabectedina/uso terapêutico , Trombospondina 1/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Células Endoteliais/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética
4.
PLoS Biol ; 21(5): e3002088, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37130348

RESUMO

Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Here, we performed serial single-cell transcriptome analyses of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven acute myeloid leukemia (AML) model in mice, which represented the transformation course in patients. We found that the Myc targets were gradually up-regulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for hematopoietic stem and progenitor cells (HSPCs) to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aa1hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 4 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134ß promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.


Assuntos
Leucemia Mieloide Aguda , Análise da Expressão Gênica de Célula Única , Humanos , Animais , Camundongos , Leucemia Mieloide Aguda/genética , Splicing de RNA/genética , RNA , Fatores de Processamento de RNA/genética , Transcriptoma/genética
5.
Mikrochim Acta ; 190(6): 236, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37219633

RESUMO

A dual-mode electrochemical sensor was fabricated for carbendazim (CBD) detection. Biomass-derived carbon loaded gold nanoparticles (AuNPs/BC) were firstly coated on a glassy carbon electrode (GCE), and then molecularly imprinted polymer (MIP) of o-aminophenol was prepared on the resulting AuNPs/BC/GCE through electrochemical method in the presence of CBD. The AuNPs/BC had excellent conductivity, large surface and good electrocatalysis, while the imprinted film presented good recognition. Thus, the obtained MIP/AuNPs/BC/GCE exhibited sensitive current response to CBD. Furthermore, the sensor displayed good impedance response to CBD. Hence, a dual-mode detection platform for CBD was established. Under optimum conditions, the linear response ranges were as wide as 1.0 nM - 15 µM (by differential pulse voltammetry, DPV) and 1.0 nM - 10 µM (by electrochemical impedance spectroscopy, EIS), and the detection limits for these two methods were as low as 0.30 nM (S/N = 3) and 0.24 nM (S/N = 3), respectively. The sensor also had high selectivity, stability and reproducibility. The sensor was applied to detect CBD in spiked real samples, including cabbage, peach, apple and lake water, and the recoveries were 85.8-108% (by DPV) and 91.4-110% (by EIS); the relative standard deviations (RSD) were 3.4-5.3% (by DPV) and 3.7-5.1% (by EIS), respectively. The results were consistent with that obtained by high-performance liquid chromatography. Therefore, this sensor is a simple and effective tool for CBD detection, and it has good application potential.


Assuntos
Ouro , Nanopartículas Metálicas , Biomassa , Reprodutibilidade dos Testes , Carbono
6.
Small Methods ; 7(7): e2300178, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37129554

RESUMO

Single-piece flexible supercapacitors (FSCs) have light and ultrathin superiorities, thereby having great potential in portable/wearable electronics. However, all the available single-piece FSCs are fabricated by in situ growth routes, which are incompatible with large-scale technology. This work designs a carboxymethyl cellulose/phytic acid/polyaniline ink, incorporating electrode with electrolyte active compositions. Based on the electrode/electrolyte active ink, a double-face print technique on mixed cellulose ester and nylon membranes to fabricate single-piece membrane-FSCs, where both sides of membranes can be utilized well, is proposed. Consequently, one FSC is measured to be only ≈0.785 cm2 in area, ≈0.021 g in weight, and ≈200 µm in thickness, while it has exceptional areal and volumetric capacitances up to 757 mF cm-2 and 37.8 F cm-3 , respectively, based on the entire device. It also exhibits high flexibility with a capacitance retention of 98% after 2000 bend cycles from 0° to 180°. The state-of-the-art FSCs are expected to have exciting prospects in portable/wearable electronics, smart reading, and flexible displays. The preparation strategy renders the massive production of large-area and mini-size arrayed FSCs, and also the "do-it-yourself" or homemade preparation, which adds more interest and designability for general users.

7.
Nat Commun ; 14(1): 1727, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977719

RESUMO

By lacking de novo purine biosynthesis enzymes, Plasmodium falciparum requires purine nucleoside uptake from host cells. The indispensable nucleoside transporter ENT1 of P. falciparum facilitates nucleoside uptake in the asexual blood stage. Specific inhibitors of PfENT1 prevent the proliferation of P. falciparum at submicromolar concentrations. However, the substrate recognition and inhibitory mechanism of PfENT1 are still elusive. Here, we report cryo-EM structures of PfENT1 in apo, inosine-bound, and inhibitor-bound states. Together with in vitro binding and uptake assays, we identify that inosine is the primary substrate of PfENT1 and that the inosine-binding site is located in the central cavity of PfENT1. The endofacial inhibitor GSK4 occupies the orthosteric site of PfENT1 and explores the allosteric site to block the conformational change of PfENT1. Furthermore, we propose a general "rocker switch" alternating access cycle for ENT transporters. Understanding the substrate recognition and inhibitory mechanisms of PfENT1 will greatly facilitate future efforts in the rational design of antimalarial drugs.


Assuntos
Malária Falciparum , Proteínas de Transporte de Nucleobases, Nucleosídeos, Nucleotídeos e Ácidos Nucleicos , Humanos , Plasmodium falciparum/metabolismo , Proteínas de Transporte de Nucleosídeos/genética , Proteínas de Transporte de Nucleosídeos/metabolismo , Proteínas de Transporte de Nucleobases, Nucleosídeos, Nucleotídeos e Ácidos Nucleicos/metabolismo , Malária Falciparum/tratamento farmacológico , Nucleosídeos de Purina/metabolismo , Inosina/metabolismo
8.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834656

RESUMO

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.


Assuntos
COVID-19 , Pancreatite , Humanos , Doença Aguda , Antígenos HLA-DR , Monócitos , Imunidade
9.
Front Oncol ; 13: 1272586, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38169749

RESUMO

Background: This study evaluated the cost-effectiveness of elacestrant (ELA) and standard-of-care (SOC) as second-/third-line treatment for pretreated estrogen receptor (ER)- positive/human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (A/MBC) in the US. Methods: The 3 health states partitioned survival model (PSM) was conducted from the perspective of the US third-party payers. The time horizon for the model lasted 10 years. Effectiveness and safety data were derived from the EMERALD trial (NCT03778931). Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from published studies. One-way sensitivity analysis as well as probabilistic sensitivity analysis were performed to observe model stability. Result: ELA led to an incremental cost-effectiveness ratio (ICER) of $8,672,360/quality-adjusted life year (QALY) gained compared with SOC in the overall population and $2,900,560/QALY gained compared with fulvestrant (FUL) in the ESR1(estrogen receptor 1) mutation subgroup. The two ICERs of ELA were significantly higher than the willingness-to-pay (WTP) threshold values of $150,000/QALY. Conclusions: ELA was not cost-effective for the second-/third-line treatment of patients with ER+/HER2-A/MBC compared with SOC in the US.

10.
Small Methods ; : e2301423, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38161268

RESUMO

Exploring special anode materials with high capacity, stable structure, and extreme temperature feasibility remains a great challenge in secondary sodium based energy systems. Here, a bimetallic Cu-Fe selenide nanosheet with refined nanostructure providing confined internal ion transport channels are reported, in which the structure improves the pseudocapacitance and reduces the charge transfer resistance for making a significant contribution to accelerating the reaction dynamics. The CuFeSe2 nanosheets have a high initial specific capacity of 480.4 mAh g-1 at 0.25 A g-1 , showing impressively excellent rate performance and ultralong cycling life over 1000 cycles with 261.1 mAh g-1 at 2.5 A g-1 . Meanwhile, it exhibits a good sodium storage performance at extreme temperatures from -20 °C to 50 °C, supporting at least 500 cycles. Besides, the CuFeSe2 ||Na3 V2 (PO4 )3 /C full cell delivers a high specific capacity of 168.5 mAh g-1 at 0.5 A g-1 and excellent feasibility for over 600 cycles long cycling. Additionally, the Na+ storage mechanisms are further revealed by ex situ X-ray diffraction (XRD) and in situ transmission electron microscopy (TEM) techniques. A feasible channelized structural design strategy is provided that inspires new instruction into the development of novel materials with high structural stability and low volume expansion rate toward the application of other secondary batteries.

11.
Front Immunol ; 13: 1062849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578487

RESUMO

Acute pancreatitis is a common gastrointestinal disease characterized by inflammation of the exocrine pancreas and manifesting itself through acute onset of abdominal pain. It is frequently associated with organ failure, pancreatic necrosis, and death. Mounting evidence describes monocytes - phagocytic, antigen presenting, and regulatory cells of the innate immune system - as key contributors and regulators of the inflammatory response and subsequent organ failure in acute pancreatitis. This review highlights the recent advances of dynamic change of numbers, phenotypes, and functions of circulating monocytes as well as their underling regulatory mechanisms with a special focus on the role of lipid modulation during acute pancreatitis.


Assuntos
Monócitos , Pancreatite Necrosante Aguda , Humanos , Doença Aguda , Inflamação
12.
Medicine (Baltimore) ; 101(42): e31065, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281118

RESUMO

We aimed to identify long non-coding RNAs (lncRNAs) aberrantly expressed in peripheral blood mononuclear cells (PBMCs) triggered by active tuberculosis (ATB), latent tuberculosis infection (LTBI), and healthy controls (HC). We examined lncRNAs expression in PBMCs isolated from children with ATB and LTBI, and from HC using RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the biological processes and signaling pathways of aberrantly expressed mRNAs. A total of 348 and 205 lncRNAs were differentially expressed in the ATB and LTBI groups, respectively, compared to the HC group. Compared to the LTBI group, 125 lncRNAs were differentially expressed in the ATB group. Compared to the HC group, 2317 mRNAs were differentially expressed in the ATB group, and 1093 mRNAs were differentially expressed in the LTBI group. Compared to the LTBI group, 2328 mRNAs were differentially expressed in the ATB group. The upregulated mRNAs were mainly enriched in neutrophil activation, neutrophil-mediated biological processes, and positive regulation of immune response in tuberculosis (TB), whereas the downregulated mRNAs were enriched in signaling pathways and structural processes, such as the Wnt signaling pathway and rDNA heterochromatin assembly. This is the first study on the differential expression of lncRNAs in PBMCs of children with TB. We identified significant differences in the expression profiles of lncRNAs and mRNAs in the PBMCs of children with ATB, LTBI, and HC, which has important implications for exploring lncRNAs as novel biomarkers for the diagnosis of TB. In addition, further experimental identification and validation of lncRNA roles could help elucidate the underlying mechanisms of Mycobacterium tuberculosis infection in children.


Assuntos
Tuberculose Latente , RNA Longo não Codificante , Tuberculose , Criança , Humanos , RNA Longo não Codificante/metabolismo , Leucócitos Mononucleares/metabolismo , Heterocromatina/metabolismo , Perfilação da Expressão Gênica , Tuberculose/genética , Tuberculose Latente/genética , Tuberculose Latente/diagnóstico , RNA Mensageiro/metabolismo , Biomarcadores/metabolismo , DNA Ribossômico
13.
Nucleic Acids Res ; 50(11): e66, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35288753

RESUMO

Alternative polyadenylation increases transcript diversities at the 3' end, regulating biological processes including cell differentiation, embryonic development and cancer progression. Here, we present a Bayesian method SCAPE, which enables de novo identification and quantification of polyadenylation (pA) sites at single-cell level by utilizing insert size information. We demonstrated its accuracy and robustness and identified 31 558 sites from 36 mouse organs, 43.8% (13 807) of which were novel. We illustrated that APA isoforms were associated with miRNAs binding and regulated in tissue-, cell type-and tumor-specific manners where no difference was found at gene expression level, providing an extra layer of information for cell clustering. Furthermore, we found genome-wide dynamic changes of APA usage during erythropoiesis and induced pluripotent stem cell (iPSC) differentiation, suggesting APA contributes to the functional flexibility and diversity of single cells. We expect SCAPE to aid the analyses of cellular dynamics and diversities in health and disease.


Assuntos
Células-Tronco Pluripotentes Induzidas , MicroRNAs , Regiões 3' não Traduzidas/genética , Animais , Teorema de Bayes , Diferenciação Celular/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Poliadenilação
14.
Int J Hyperthermia ; 39(1): 230-238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35094613

RESUMO

OBJECTIVE: This study was aimed at comparing the outcomes of high-intensity focused ultrasound (HIFU) with those of uterine artery embolization (UAE) and traditional surgeries for treating symptomatic uterine fibroids. MATERIALS AND METHODS: We searched the following databases from their beginning to 5 November 2021: PubMed, Medline, Embase and Cochrane Library. RESULTS: Overall, 21 studies were included in this meta-analysis. The results revealed that HIFU had a higher re-intervention rate than UAE (relative risk [RR] = 4.06, 95% confidence interval [CI]: 2.47-6.69) and offered no significant advantages in reducing the symptom severity score (SSS) (mean difference [MD] = 17.01, 95% CI: 10.25-23.77) and improving the health-related quality of life (HRQoL) score (MD= -18.32, 95% CI: -24.87 to -11.78) in the treatment of symptomatic uterine fibroids. However, compared with UAE, HIFU may be associated with a higher pregnancy rate (RR = 17.44, 95% CI: 2.40-126.50) and may have a significant advantage in shortening pregnancy interval and preserving ovarian function. Moreover, upon comparing HIFU with traditional surgical treatments, the HIFU group showed significantly improved HRQoL score (MD = 2.25, 95% CI: 1.15-3.35), but the re-intervention rate (RR = 1.65, 95% CI: 0.59-4.57), pregnancy rate (RR = 1.01, 95% CI: 0.90-1.13), SSS and ovarian function did not significantly differ between the two groups. CONCLUSIONS: Although HIFU has relatively high re-intervention rate, it may offer a higher pregnancy rate and shorter pregnancy interval with little influence on ovarian function, thus making it an attractive option for treating symptomatic fibroids in young women who wish to plan a pregnancy in the future.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Neoplasias Uterinas , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Leiomioma/cirurgia , Leiomioma/terapia , Gravidez , Qualidade de Vida , Resultado do Tratamento , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/terapia
15.
Signal Transduct Target Ther ; 7(1): 9, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-35027529

RESUMO

Lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, and epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing. We investigated their differences in genetic amplification, cellular compositions, and expression modules. We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells, and had distinct cellular composition modules associated with poor survival of lung cancer. Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression. Moreover, we identified subclusters with proliferating and differentiating properties in AT2 and basal cells. Overexpression assays of ten genes, including sub-cluster markers AQP5 and KPNA2, further indicated their functional roles, providing potential targets for early diagnosis and treatment in lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Análise de Sequência de RNA , Análise de Célula Única , Transcrição Gênica , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
17.
Sci Data ; 8(1): 309, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845251

RESUMO

Hematopoietic stem cells (HSCs) lie at the top of the differentiation hierarchy. Although HSC and their immediate downstream, multipotent progenitors (MPP) have full multilineage differentiation capacity, only long-term (LT-) HSC has the capacity of long-term self-renewal. The heterogeneity within the HSC population is gradually acknowledged with the development of single-cell RNA sequencing and lineage tracing technologies. Transcriptional and post-transcriptional regulations play important roles in controlling the differentiation and self-renewal capacity within HSC population. Here we report a dataset comprising short- and long-read RNA sequencing for mouse long- and short-term HSC and MPP at bulk and single-cell levels. We demonstrate that integrating short- and long-read sequencing can facilitate the identification and quantification of known and unannotated isoforms. Thus, this dataset provides a groundwork for comprehensive and comparative studies on transcriptional diversity and heterogeneity within different HSC cell types.


Assuntos
Diferenciação Celular/genética , Células-Tronco Hematopoéticas/citologia , Análise de Sequência de RNA , Animais , Feminino , Hematopoese , Camundongos , Camundongos Endogâmicos C57BL
18.
Angew Chem Int Ed Engl ; 60(47): 25055-25062, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34490697

RESUMO

Herein, we explore a general Cu2-x S nanocube template-assisted and reverse cation exchange-mediated growth strategy for fabricating hollow multinary metal sulfide. Unlike the traditional cation exchange method controlled by the metal sulfide constant, the introduction of tri-n-butylphosphine (TBP) can reverse cation exchange to give a series of hollow metal sulfides. A variety of hollow multinary metal sulfide cubic nanostructures has been demonstrated while preserving anisotropic shapes to the as-synthesized templates, including binary compounds (CdS, ZnS, Ag2 S, PbS, SnS), ternary compound (CuInS2 , Znx Cd1-x S), and quaternary compound (single-atom platinum anchored Znx Cd1-x S; Znx Cd1-x S-Pt1 ). Experimental and density functional theory (DFT) calculations show that the hollow metal sulfide semiconductors obtained could significantly improve the separation and migration of photogenerated electron-hole pairs. Owing to the efficient charge transfer, the Znx Cd1-x S-Pt1 exhibited outstanding photocatalytic performance of CO2 to CO, with the highest CO generation rate of 75.31 µmol h-1 .

19.
Curr Res Immunol ; 2: 104-119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532703

RESUMO

Natural infection with Plasmodium parasites, the causative agents of malaria, occurs via mosquito vectors. However, most of our knowledge of the immune response to the blood stages of Plasmodium is from infections initiated by injection of serially blood-passaged infected red blood cells, resulting in an incomplete life cycle in the mammalian host. Vector transmission of the rodent malaria parasite, Plasmodium chabaudi chabaudi AS has been shown to give rise to a more attenuated blood-stage infection in C57Bl/6J mice, when compared to infections initiated with serially blood-passaged P. chabaudi-infected red blood cells. In mouse models, the host immune response induced by parasites derived from natural mosquito transmission is likely to more closely resemble the immune responses to Plasmodium infections in humans. It is therefore important to determine how the host response differs between the two types of infections. As the spleen is considered to be a major contributor to the protective host response to P. chabaudi, we carried out a comparative transcriptomic analysis of the splenic response to recently mosquito-transmitted and serially blood-passaged parasites in C57Bl/6J mice. The attenuated infection arising from recently mosquito-transmitted parasites is characterised by an earlier and stronger myeloid- and IFNγ-related response. Analyses of spleen lysates from the two infections similarly showed stronger or earlier inflammatory cytokine and chemokine production in the recently mosquito-transmitted blood-stage infections. Furthermore, tissue macrophages, including red pulp macrophages, and IFNγ-signalling in myeloid cells, are required for the early control of P. chabaudi recently mosquito-transmitted parasites, thus contributing to the attenuation of mosquito-transmitted infections. The molecules responsible for this early activation response to recently-transmitted blood-stage parasites in mice would be important to identify, as they may help to elucidate the nature of the initial interactions between blood-stage parasites and the host immune system in naturally transmitted malaria.

20.
Signal Transduct Target Ther ; 6(1): 289, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326311

RESUMO

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.


Assuntos
Imunidade Adaptativa , COVID-19/imunologia , Imunidade Inata , Linfócitos/imunologia , Complicações Infecciosas na Gravidez/imunologia , SARS-CoV-2/imunologia , Adulto , Proteína C-Reativa/imunologia , Feminino , Humanos , Interleucina-6/imunologia , Gravidez , Estudos Retrospectivos , Análise de Sequência de RNA , Análise de Célula Única
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