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1.
Cell Discov ; 8(1): 39, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35501312

RESUMO

The entity of DNA N6-methyladenine (6mA) in mammals remains elusive and subsequently its roles in diseases are poorly understood. Here we exploited a bacterial DNA contamination-free and ultrasensitive UHPLC-MS/MS assay to reassess DNA 6mA in human glioblastomas and unveiled that DNA 6mA (~0.08 ppm) is extremely rare. By the use of two independent heavy stable isotope-labeling strategies, we further prove that the observed 6mA is solely generated by DNA polymerase-mediated misinocorporation. In vitro experiments point toward that the generation of misincorporated DNA 6mA is associated with the cellular stresses-caused release of RNA N6-methyladenine (m6A) nucleoside, which is profoundly inhibited by hypoxia milieu. Consistently, compared with normal brain tissues, DNA 6mA decreases in hypoxic human gliomas. Our data also strongly support that rare DNA 6mA rather than relatively abundant DNA 5-methylcytosine and 5-hydroxymethylcytosine is a hallmark of poor prognosis of IDH1/2 mutation-absent glioblastoma patients, reflecting the incidence of cytotoxic stresses and subsequent release of m6A nucleoside. The released m6A nucleoside may selectively preserve a subset of the glioblastoma cells and stimulate their stemness and proliferation. Noteworthily, demethylation-inhibiting IDH1 mutation increases the DNA 6mA content in human gliomas, but the depletion of the demethylase candidate ALKBH1 fails to do so, together suggesting the presence of other unknown 6mA demethylase for erasing misincorporated DNA 6mA. This is the first report on the identification of the misincorporated 6mA together with its origin and roles in diseases.

2.
Hum Vaccin Immunother ; 18(1): 2040330, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35321627

RESUMO

As an acute respiratory infectious disease, COVID-19 threatens the safety of global public health. Given the current lack of specific treatment against this disease, research and development of vaccines have become sharp weapons for overcoming the pandemic. mRNA vaccines have become the lead in COVID-19 vaccination strategies due to their advantages, such as rapid industrial production and efficacy. A total of 137 COVID-19 vaccines have entered the clinical trial stage, among which 23 are mRNA vaccines, accounting for 17% of the total vaccines. Herein, we summarize the research and developmental processes of mRNA vaccines as well as the approach for protecting the human body against infection. Focusing on the latest clinical trial data of two COVID-19 mRNA vaccines from Pfizer and Modena, we discuss their effectiveness and safety. Finally, we analyze the challenges and problems that mRNA vaccines face in controlling the COVID-19 pandemic.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Vacinas Sintéticas
3.
Chem Res Toxicol ; 35(3): 387-391, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35263988

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that causes endless pain for patients and accounts for thousands of deaths worldwide. The development of an effective AML treatment is a topic of ongoing interest. Here, we demonstrated that a pyroptosis inhibitor necrosulfonamide (NSA) can selectively induce highly toxic double-strand breaks and kill AML cells. Mechanistically, reactive oxygen species (ROS) were the key effectors mediating the toxicity of NSA. These results probably indicate that NSA is a novel candidate for the treatment of AML.


Assuntos
Apoptose , Leucemia Mieloide Aguda , Acrilamidas , Linhagem Celular Tumoral , DNA , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Espécies Reativas de Oxigênio , Sulfonamidas
4.
IEEE Trans Image Process ; 31: 2433-2448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35259105

RESUMO

Recently, tensor Singular Value Decomposition (t-SVD)-based low-rank tensor completion (LRTC) has achieved unprecedented success in addressing various pattern analysis issues. However, existing studies mostly focus on third-order tensors while order- d ( d ≥ 4 ) tensors are commonly encountered in real-world applications, like fourth-order color videos, fourth-order hyper-spectral videos, fifth-order light-field images, and sixth-order bidirectional texture functions. Aiming at addressing this critical issue, this paper establishes an order- d tensor recovery framework including the model, algorithm and theories by innovatively developing a novel algebraic foundation for order- d t-SVD, thereby achieving exact completion for any order- d low t-SVD rank tensors with missing values with an overwhelming probability. Emperical studies on synthetic data and real-world visual data illustrate that compared with other state-of-the-art recovery frameworks, the proposed one achieves highly competitive performance in terms of both qualitative and quantitative metrics. In particular, as the observed data density becomes low, i.e., about 10%, the proposed recovery framework is still significantly better than its peers. The code of our algorithm is released at https://github.com/Qinwenjinswu/TIP-Code.

5.
Science ; 375(6580): 515-522, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35113693

RESUMO

The discovery of N6-methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic DNA sample into species of interest, genomic regions, and sources of contamination. Applying this method, we observed high-resolution 6mA deposition in two protozoa. We found that commensal or soil bacteria explained the vast majority of 6mA in insect and plant samples. We found no evidence of high abundance of 6mA in Drosophila, Arabidopsis, or humans. Plasmids used for genetic manipulation, even those from Dam methyltransferase mutant Escherichia coli, could carry abundant 6mA, confounding the evaluation of candidate 6mA methyltransferases and demethylases. On the basis of this work, we advocate for a reassessment of 6mA in eukaryotes.


Assuntos
Metilação de DNA , DNA/química , Desoxiadenosinas/análise , Eucariotos/genética , Animais , Arabidopsis/genética , Neoplasias Encefálicas/genética , Chlamydomonas reinhardtii/genética , DNA/genética , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Fúngico/química , DNA Fúngico/genética , DNA de Protozoário/química , DNA de Protozoário/genética , Drosophila melanogaster/genética , Drosophila melanogaster/microbiologia , Epigênese Genética , Escherichia coli/genética , Eucariotos/metabolismo , Glioblastoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucócitos Mononucleares/química , Metagenômica , Plasmídeos , Análise de Sequência de DNA , Tetrahymena thermophila/genética
7.
EBioMedicine ; 76: 103861, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35124429

RESUMO

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).


Assuntos
Redes Reguladoras de Genes/genética , Genoma Humano , Ácido Hialurônico/metabolismo , RNA Viral/genética , SARS-CoV-2/genética , Antagomirs/metabolismo , Proteínas Argonauta/genética , Sequência de Bases , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Progressão da Doença , Elementos Facilitadores Genéticos/genética , Humanos , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Ácido Hialurônico/sangue , MicroRNAs/genética , RNA Viral/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Regulação para Cima
8.
Blood Adv ; 6(1): 339-357, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34547770

RESUMO

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Irmãos , Doadores não Relacionados
9.
Environ Pollut ; 294: 118630, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871645

RESUMO

This study investigated the characteristics of air multi-pollutants emitted during typical electronic waste (e-waste) dismantling processes and assessed their risks to the environment and human health. Concentrations of total volatile organic compounds (TVOCs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in a typical e-waste dismantling workshop were 137 µg/m3, 135 ng/m3 and 42 ng/m3, respectively, which were lower than those without emission control measures. The partial removal of pollutants due to the emission control measures also decreased the ozone formation potential and non-cancer risk of volatile organic compounds (VOCs). In the workshop, the lifetime cancer risk (LCR) of VOCs (8.1 × 10-5) was close to the recommended values. Conversely, the LCR of PAHs (3.6 × 10-5) and the total exposure index of PBDEs (19 ng/d) were remarkably lower than the recommended values of 10-3 and that without emission control measures, respectively. Meanwhile, the concentrations of TVOCs, polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), PBDEs, and PAHs in the outlet were approximately 10-30 times higher than those in the workshop. In addition, the LCR of TVOCs within a 5-km radius area remained higher than the accepted value (10-6), and the inhalation exposure risk of PCDD/Fs within a 20-km radius area was five times higher than the recommended value. Therefore, the emissions from e-waste recycling processes should be considered as an important source of air pollution, and more efficient control measures should be taken in the future.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Resíduo Eletrônico , Poluentes Ambientais , Dibenzodioxinas Policloradas , Poluentes Atmosféricos/análise , China , Dibenzofuranos , Resíduo Eletrônico/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , Éteres Difenil Halogenados/análise , Humanos , Dibenzodioxinas Policloradas/análise , Medição de Risco
10.
Chemosphere ; 289: 133161, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34883127

RESUMO

Abnormal elevation of indispensable steroid hormone estrogens and exposure to exogenous estrogen-like compounds pose adverse health effects to aquatic animals and human alike. These compounds generally display functionally important estrogenic activity even at extremely low picomolar concentrations. In this study we identified one critical but lethal gene (TAF1) that remarkably represses estrogenic activity. This gene is selected as a candidate for genetically modulating an estrogen-responding cell line. To overcome its lethality, instead of adopting a gene knockout strategy, we developed a transient TAF1 depletion strategy using a designed small interfering RNA. By the transient knockdown of TAF1 in the estrogen-responding reporter cell line, the maximum induction signals for endogenous estrogen 17ß-estradiol (E2) and environmental estrogens 17α-ethynyl estradiol (EE2) and bisphenol compounds were enhanced by 4.8-13.3 folds. The limit of detection for EE2 is about 8 × 10-15 mol/L. Moreover, by the established method, trace estrogenic activity (14.7-24.2 pg E2 equivalents (E2Eq)/L) can be detected in a portion of Tap water samples.


Assuntos
Estrogênios , Poluentes Químicos da Água , Animais , Estradiol/análise , Estrogênios/análise , Estrona/análise , Etinilestradiol/análise , Humanos , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
11.
Blood Adv ; 6(3): 828-847, 2022 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-34551064

RESUMO

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Recidiva , Indução de Remissão
13.
Bone Marrow Transplant ; 57(1): 6-10, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34413470

RESUMO

There are several statistical programmes to compute direct adjusted survival estimates from results of the Cox proportional hazards model. However, when used to analyze observational databases with large sample sizes or highly stratified treatment groups such as in registry-related datasets, these programmes are inefficient or unable to generate confidence bands and simultaneous p values. Also, these programmes do not consider potential left-truncation in retrospectively collected data. To address these deficiencies we developed a new SAS macro %adjsurvlt() able to produce direct adjusted survival estimates based on a stratified Cox model. The macro has improved computational performance and is able to handle left-truncated and right-censored time-to-event data. Several mechanisms were implemented to improve computational efficiency including choosing matrix operations over do-loops and reducing dimensions of co-variate matrices. Compared to the latest SAS macro, %adjsurvlt() used < 0.1% computational time to process a dataset with 100 treatment cohorts and a sample size of 20,000 and showed similar computational efficiency when analyzing left-truncated and right-censored data. We illustrate use of %adjsurvlt() to compare retrospectively collected survival data of 2 transplant cohorts.


Assuntos
Estudos Retrospectivos , Humanos , Modelos de Riscos Proporcionais , Tamanho da Amostra , Análise de Sobrevida
14.
Colloids Surf A Physicochem Eng Asp ; 633: 127849, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34744314

RESUMO

Hydroxychloroquine sulfate (HCQ) is a well-established antimalarial drug that has received considerable attention during the COVID-19 associated pneumonia epidemic. Gelatin is a multifunctional biomacromolecule with pharmaceutical applications and can be used to deliver HCQ. The effect of HCQ on the gelation behaviors, water mobility, and structure of gelatin was investigated to understand the interaction between the drug and its delivery carrier. The gel strength, hardness, gelling (Tg) and melting (Tm) temperatures, gelation rate (kgel), and water mobility of gelatin decreased with increasing amounts of HCQ. The addition of HCQ led to hydrogen bonding that interfered with triple helix formation in gelatin. Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometer (XRD) analysis further confirmed that the interaction between HCQ and gelatin is primarily through hydrogen bonding. Atomic force microscopy (AFM) revealed that higher content of HCQ resulted in more and larger aggregates in gelatin. These results provide not only an important understanding of gelatin for drug delivery design but also a basis for the studying interactions between a drug and its delivery carrier.

15.
BMC Cancer ; 22(1): 326, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337279

RESUMO

BACKGROUND: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy. METHODS: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China. RESULTS: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001). CONCLUSIONS: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Anal Chem ; 93(47): 15567-15572, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34783527

RESUMO

To date, subchromatin structure-based quantification of epigenetic DNA modifications is limited. Matrix attachment regions (MARs), an important subchromatin structure, contain DNA elements that specifically bind chromatin to the nuclear matrix in eukaryotes and are involved in a number of diseases. Here, we exploited a high-salt extraction-based subchromatin fractionation approach for the isolation of MAR DNA and other fractions and further developed heavy stable isotope-diluted ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for the specific quantification of epigenetic DNA modifications in the subchromatin structures. By this approach, we showed for the first time that the content of a DNA demethylation intermediate, 5-hydroxymethylcytosine (5hmdC), in MARs decreased significantly in four tested cell lines compared to the contents in genomic DNA. In particular, the content of DNA 5hmdC in the MARs of 293T cell lines decreased the most at approximately 41.09%. Together, our findings implicate that MAR DNA is less sensitive than genomic DNA to DNA demethylation.


Assuntos
Regiões de Interação com a Matriz , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , DNA/genética , Epigênese Genética , Isótopos
17.
Front Med (Lausanne) ; 8: 753257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778316

RESUMO

Purpose: To assess the potential of a health examination center-based screening model in improving service for uncorrected refractive error. Methods: Individuals aged ≥18 years undergoing the routine physical examinations at a tertiary hospital in the northeast China were invited. Presenting visual acuity, noncycloplegic autorefraction, noncontact tonometry, fundus photography, and slit-lamp examination were performed. Refractive error was defined as having spherical equivalent ≤ -0.75 D or ≥ +1 D and uncorrected refractive error was considered as refractive error combined with presenting visual acuity < 6/12 in the better eye. Costs for the screening were assessed. Results: A total of 5,284 participants (61 ± 14 years) were included. The overall prevalence of myopia and hyperopia was 38.7% (95% CI, 37.4-40.0%) and 23.5% (95% CI, 22.3-24.6%), respectively. The prevalence of uncorrected refractive error was 7.85% (95% CI, 7.13-8.58%). Women (p < 0.001 and p = 0.003), those with age ≥ 70 years (p < 0.001 and p = 0.003), and myopia (p < 0.001 and p < 0.001) were at higher risk of uncorrected refractive error and uncorrected refractive error-related visual impairment. Spectacle coverage rate was 70.6% (95% CI, 68.2-73.0%). The cost to identify a single case of refractive error and uncorrected refractive error was US$3.2 and US$25.2, respectively. Conclusion: The prevalence of uncorrected refractive error is high in the urban Chinese adults. Health examination center-based refractive error screening is able to provide an efficient and low-cost model to improve the refractive services in China.

18.
Genomics ; 113(6): 4245-4253, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34793949

RESUMO

Heterosis refers to the superior phenotypes observed in hybrids. Cytoplasmic male sterility (CMS) system plays an important role in cotton heterosis utilization. However, the global gene expression patterns of CMS-D2 and its interaction with the restorer gene Rf1 remain unclear. Here, the full-length transcript sequencing was performed in anthers of the CMS-D2 restorer line using PacBio single-molecule real-time sequencing technology. Combining PacBio SMRT long-read isoforms and Illumina RNA-seq data, 107,066 isoforms from 44,338 loci were obtained, including 10,086 novel isoforms of novel genes and 66,419 new isoforms of known genes. Totally 56,572 alternative splicing (AS) events, 1146 lncRNAs, 61 fusion transcripts and 10,466 genes exhibited alternative polyadenylation (APA), and 60,995 novel isoforms with predicted open reading frames (ORFs) were further identified. Furthermore, the specifically expressed genes in restorer line were selected and confirmed by qRT-PCR. These findings provide a basis for upland cotton genome annotation and transcriptome research, and will help to reveal the molecular mechanism of interaction between Rf1 and CMS-D2 cytoplasm.


Assuntos
RNA Longo não Codificante , Transcriptoma , Fertilidade/genética , Estudos de Associação Genética , RNA Longo não Codificante/genética , RNA-Seq
19.
Huan Jing Ke Xue ; 42(11): 5193-5200, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708958

RESUMO

The emission characteristics of VOCs from three typical rubber manufacture industries were studied by GC-MS/FID. Maximum incremental reactivity(MIR) and fractional aerosol coefficient(FAC) were employed to evaluate the ozone formation potential(OFP) and secondary organic aerosol(SOA) formation potential. The results show that the VOC types emitted from the manufacturing of rubber products mainly include alkanes, ketones, aldehydes, alcohols, and benzene series. For traditional rubber products manufactured through rubber mixing and vulcanization, the main pollutants are ketones and alcohols, whereas for production processes involving gluing and painting, the main pollutants belong to the benzene series. In terms of ozone impact, the traditional processes contribute to ozone formation mainly through oxygenated hydrocarbons. In industries that utilize adhesives and paints, the extensive use of these organic solvents lead to a significantly higher contribution of the benzene series than other VOC species to ozone formation; the benzene series account for 82.9% of the total contribution. In terms of SOA impact, the benzene series are the main contributor to SOA, whereas the contribution of VOCs from traditional processes is small; hence, SOA primarily originates from the gluing and painting processes. Therefore, in traditional production of rubber products through rubber mixing and vulcanization, the emission of oxygenated hydrocarbons should be preferentially controlled, whereas for rubber industries utilizing gluing and painting processes, the emission of benzene series should be preferentially controlled.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Borracha , Compostos Orgânicos Voláteis/análise
20.
Front Cell Dev Biol ; 9: 724310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604224

RESUMO

Dermal papillae are a target of androgen action in patients with androgenic alopecia, where androgen acts on the epidermis of hair follicles in a paracrine manner. To mimic the complexity of the dermal papilla microenvironment, a better culture model of human dermal papilla cells (DPCs) is needed. Therefore, we evaluated the inhibitory effect of dihydrotestosterone (DHT)-treated two-dimensional (2D)- and 3D-cultured DPCs on hair follicle growth. 2D- and 3D-cultured DPC proliferation was inhibited after co-culturing with outer root sheath (ORS) cells under DHT treatment. Moreover, gene expression levels of ß-catenin and neural cell adhesion molecules were significantly decreased and those of cleaved caspase-3 significantly increased in 2D- and 3D-cultured DPCs with increasing DHT concentrations. ORS cell proliferation also significantly increased after co-culturing in the control-3D model compared with the control-2D model. Ki67 downregulation and cleaved caspase-3 upregulation in DHT-treated 2D and 3D groups significantly inhibited ORS cell proliferation. Sequencing showed an increase in the expression of genes related to extracellular matrix synthesis in the 3D model group. Additionally, the top 10 hub genes were identified, and the expression of nine chemokine-related genes in DHT-treated DPCs was found to be significantly increased. We also identified the interactions between transcription factor (TF) genes and microRNAs (miRNAs) with hub genes and the TF-miRNA coregulatory network. Overall, the findings indicate that 3D-cultured DPCs are more representative of in vivo conditions than 2D-cultured DPCs and contribute to our understanding of the molecular mechanisms underlying androgen-induced alopecia.

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