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1.
Front Genet ; 12: 705753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721519

RESUMO

The Hui minority is predominantly composed of Chinese-speaking Islamic adherents distributed throughout China, of which the individuals are mainly concentrated in Northwest China. In the present study, we employed the length and sequence polymorphisms-based typing system of 231 molecular markers, i.e., amelogenin, 22 phenotypic-informative single nucleotide polymorphisms (PISNPs), 94 identity-informative single nucleotide polymorphisms (IISNPs), 24 Y-chromosomal short tandem repeats (Y-STRs), 56 ancestry-informative single nucleotide polymorphisms (AISNPs), 7 X-chromosomal short tandem repeats (X-STRs), and 27 autosomal short tandem repeats (A-STRs), into 90 unrelated male individuals from the Chinese Northwest Hui group to comprehensively explore its forensic characteristics and genetic background. Total of 451 length-based and 652 sequence-based distinct alleles were identified from 58 short tandem repeats (STRs) in 90 unrelated Northwest Hui individuals, denoting that the sequence-based genetic markers could pronouncedly provide more genetic information than length-based markers. The forensic characteristics and efficiencies of STRs and IISNPs were estimated, both of which externalized high polymorphisms in the Northwest Hui group and could be further utilized in forensic investigations. No significant departure from the Hardy-Weinberg equilibrium (HWE) expectation was observed after the Bonferroni correction. Additionally, four group sets of reference population data were exploited to dissect the genetic background of the Northwest Hui group separately from different perspectives, which contained 26 populations for 93 IISNPs, 58 populations for 17 Y-STRs, 26 populations for 55 AISNPs (raw data), and 109 populations for 55 AISNPs (allele frequencies). As a result, the analyses based on the Y-STRs indicated that the Northwest Hui group primarily exhibited intimate genetic relationships with reference Hui groups from Chinese different regions except for the Sichuan Hui group and secondarily displayed close genetic relationships with populations from Central and West Asia, as well as several Chinese groups. However, the AISNP analyses demonstrated that the Northwest Hui group shared more intimate relationships with current East Asian populations apart from reference Hui group, harboring the large proportion of ancestral component contributed by East Asia.

2.
Ecotoxicol Environ Saf ; 228: 112954, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34739934

RESUMO

As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl2 treatment could induce kidney damage. Meanwhile, NiCl2 treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl2-mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl2. The results showed that NAC significantly suppressed the NiCl2-mediated oxidative stress and mitigated NiCl2-induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl2-induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl2-induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl2-induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/- 8/- 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl2-mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches.

3.
Opt Express ; 29(24): 39685-39695, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809326

RESUMO

We propose and demonstrate a circular-side octagonal microcavity (COM) semiconductor laser with a spatially distributed current injection for manipulating the lasing modes. There are two types of high-quality-factor whispering-gallery (WG) modes with distinct field patterns in a COM: the four-bounced quadrilateral modes and the eight-bounced octagonal modes. By designing two separated p-electrodes, the COM laser is divided into two regions that are pumped independently to select specific modes for lasing. The two types of WG modes lase simultaneously when the two regions are injected with equivalent currents. Degeneracy removal of the quadrilateral modes is observed in both simulation and experiment when the two regions are injected with inequivalent currents. The quadrilateral modes are suppressed when one of the two regions is un-injected or biased with a negative current, and single-octagonal-mode lasing is realized. The results show that the lasing modes can be efficiently manipulated with the spatially distributed current injection considering the distinct field patterns of different WG modes in the microcavities, which can promote the practical application of the microcavity lasers.

4.
ACS Omega ; 6(45): 30442-30450, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34805674

RESUMO

A theoretical study of geometrical structures, electronic properties, and spectral properties of single-atom transition metal-doped boron clusters MB24 (M = Sc, V, and Mn) is performed using the CALYPSO approach for the global minimum search, followed by density functional theory calculations. The global minima obtained for the VB24 and MnB24 clusters correspond to cage structures. Interestingly, the global minima obtained for the ScB24 cluster tend to a three-ring tubular structure. Population analyses and valence electron density analyses reveal that partial electrons on transition-metal atoms transfer to boron atoms. The localized orbital locator of MB24 (M = Sc, V, and Mn) indicates that the electron delocalization of ScB24 is stronger than that of VB24 and MnB24, and there is no obvious covalent bond between doped metals and B atoms. The spin density and spin population analyses reveal that MB24 (M = Sc, V, and Mn) have different spin characteristics which are expected to lead to interesting magnetic properties and potential applications in molecular devices. The calculated spectra indicate that MB24 (M = Sc, V, and Mn) has meaningful characteristic peaks that can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of these single-atom transition metal-doped boron clusters. Our work enriches the database of geometrical structures of doped boron clusters and can provide an insight into new doped boron clusters.

5.
Sci Rep ; 11(1): 21348, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725421

RESUMO

Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegenerative diseases. Here, we investigated the possible role of VLCFA-lipids in frontotemporal dementia (FTD), which is a leading cause of younger-onset dementia. Using quantitative discovery lipidomics, we identified three VLCFA-lipid species that were significantly increased in FTD brain compared to controls, with strong correlations with ELOVL4. Increases in ELOVL4 expression correlated with significant decreases in the membrane-bound synaptophysin in FTD brain. Furthermore, increases in ABCD1 expression correlated with increases in VLCFA-lipids. We uncovered a new pathomechanism that is pertinent to understanding the pathogenesis of FTD.

6.
Ann Transl Med ; 9(17): 1382, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733934

RESUMO

Background: Breast cancer (BC) is a common tumor that seriously affects women's physical/mental health and even life. BC invasion and metastasis are still the main causes of mortality in BC patients. Exosomal long non-coding RNAs (exo-lncRNA) play an important role in cell communication and can help to understand better the physiological and pathological conditions that result from BC. This study investigates new potential targets and functions of the expression profiles of exo-lncRNAs in BC patients through high-throughput screening and bioinformatics. Methods: Samples were collected from two BC patients and one healthy subject. The serum exosomal RNAs were subsequently purified, and a library was established for quality inspection and sequencing. The resultant data was compared with the reference data to obtain the differential expression of exo-lncRNAs, and predict the target genes. To obtain the final results, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes. Results: After a comprehensive comparison of the BC patients and healthy subjects, we discovered five up-regulated exo-lncRNAs and six down-regulated exo-lncRNAs of interest. Combining our results with a literature review and screening, we found that VIM-AS1, SNHG8, and ELDR play a role in the progression of BC, with VIM-AS1 predicting 35 target miRNAs; SNHG8 predicting 12 target miRNAs, and ELDR predicting 24 target miRNAs. Target prediction considered that the target gene of VIM-AS1 was VIM and that the target gene of SNHG8 was PRSS12. GO enrichment analysis showed that VIM mainly played a role in cell processes, biological regulation, metabolic regulation, and molecular adhesion, while PRSS12 was enriched through cell metabolism, catalytic activity, and hydrolase activity. KEGG pathway enrichment results also indicated how the VIM protein functions in cancer development through the viral infection signaling pathway and miRNA signaling pathway. Conclusions: There is a significant difference in the expression profiles of serum exo-lncRNAs between BC patients and healthy individuals. This may be closely related to BC's occurrence, development, and metastasis, and therefore provides a theoretical basis for more in-depth studies into exo-lncRNA.

8.
Sci Total Environ ; : 151380, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780825

RESUMO

This present study investigated detoxification mechanisms of leguminous forage Trifolium pratense L. (red clover) seedlings upon exposure to Ag ions (Ag+) on an atomic level. Depressed plant growth (maximum inhibition rate: 46.57%) and significantly altered antioxidase/antioxidant substances levels (maximum inhibition rate: 65.45%/55.41%) revealed that the physiological metabolism was disturbed. Notable lesions were observed in both leaf and root cells at 588 µM Ag+ treatment. All differentially expressed genes (DEGs) were remarkably mapped to biological metabolism related pathways. Red clover seedlings were speculated to initially transform and immobilize Ag+ in the culture medium, then transporting and fixing them inside the cell, mainly as unreduced Ag+ bound to oxygen-, nitrogen-, sulfur-, chloride-containing biological molecules. A portion of Ag+ was reduced to Ag0 and aggregated to form crystalline argentiferous nanoparticles. Effective reducing agents such as alcohols, carboxylic acid, and etc, which are capable of coordinating heavy metals to reduce and stabilize them, were assumed to play a role in Ag+ reduction. The research results are of great value to understand the defense and tolerance mechanisms of red clover to Ag+ and explore the main existing forms of Ag+ in vivo and in vitro, which could indicate contamination condition in regional ecological environment such as mining area and its potential effects.

9.
Front Neurol ; 12: 740136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795628

RESUMO

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period. Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded. Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p < 0.001; 25.9 vs. 20.3%, p < 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322-3.059, p = 0.001). Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.

10.
Medicine (Baltimore) ; 100(41): e27469, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731124

RESUMO

BACKGROUND: We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents. MATERIALS AND METHODS: A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10. RESULTS: Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76-1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33-0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29-0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80-1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65-1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60-1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70-1.16; P = .41). CONCLUSIONS: Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.


Assuntos
Acetanilidas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Acetanilidas/administração & dosagem , Acetanilidas/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Antagonistas Colinérgicos/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/epidemiologia , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Taquicardia/induzido quimicamente , Taquicardia/epidemiologia , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Infecções Urinárias/induzido quimicamente , Infecções Urinárias/epidemiologia , Baixa Visão/induzido quimicamente , Baixa Visão/epidemiologia , Xerostomia/induzido quimicamente , Xerostomia/epidemiologia
11.
J Hazard Mater ; : 127654, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34772557

RESUMO

Up to now, solvent extraction not only recycle valuable metals (i.e., Ni, Co, Mn and Li) from the leach liquor of spent cathode materials, but also apply to treat spent electrolyte. This paper summarizes the development of solvent extraction in the field of recycling spent lithium-ion batteries (LIBs) from the aspects of principle, technology and industrialization. Meanwhile, the paper also comments on the challenges and opportunities for the solvent extraction facing in the recycling of spent LIBs.

12.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5027-5037, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738398

RESUMO

To obtain the chemical profile of Tibetan medicinal plant ″Bangga″, the present study established the HPLC fingerprint of ″Bangga″ and inferred common chemical constituents of its two original plants, Aconitum tanguticum and A. naviculare by LC-MS. The HPLC analysis was performed on a Kromasil 100 C_8 column(4.6 mm×250 mm, 5 µm) with acetonitrile(A)-0.1% formic acid in water(B) as mobile phase in a gradient elution mode. Besides, the flow rate was set at 1 mL·min~(-1) and the column temperature was 35 ℃. The detection wavelength was set at 255 nm and the injection volume was 10 µL. Seventeen batches of ″Bangga″ samples were analyzed and the HPLC fingerprint was established under the above conditions. Similarity evaluation was performed using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012). As a result, 16 common peaks were selec-ted and the similarity values of 17 batches of ″Bangga″ were in the range of 0.702-0.966. Furthermore, one batch of A. tanguticum and one batch of A. naviculare were analyzed by LC-MS/MS and 74 common compounds were inferred, including 10 phenolic acids, 26 flavonoids, and 38 alkaloids. The established method, with good separation and strong specificity, is simple and feasible, and can be used for the quality control of ″Bangga″ and identification of its two original plants. A. tanguticum and A. naviculare are similar in chemical composition and component content, but are quite different in the content of flavonoids.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Espectrometria de Massas em Tandem , Tibet
13.
Clin Cancer Res ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740924

RESUMO

PURPOSE: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy. EXPERIMENTAL DESIGN: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-seq datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo Results: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function. CONCLUSIONS: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

14.
Leukemia ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741118

RESUMO

Myelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). The JAK inhibitor Ruxolitinib can reduce constitutional symptoms but it does not substantially improve bone marrow fibrosis. Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors. Here, we show that genetic ablation of Pim1 blocked the development of myelofibrosis induced by Jak2V617F and MPLW515L. Pharmacologic inhibition of Pim1 with a second-generation Pim kinase inhibitor TP-3654 significantly reduced leukocytosis and splenomegaly, and attenuated bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of MF. Combined treatment of TP-3654 and Ruxolitinib resulted in greater reduction of spleen size, normalization of blood leukocyte counts and abrogation of bone marrow fibrosis in murine models of MF. TP-3654 treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, we show that TP-3654 treatment significantly inhibits mTORC1, MYC and TGF-ß signaling in Jak2V617F mutant hematopoietic cells and diminishes the expression of fibrotic markers in the bone marrow. Collectively, our results suggest that Pim1 plays an important role in the pathogenesis of MF, and inhibition of Pim1 with TP-3654 might be useful for treatment of MF.

15.
Nucleic Acids Res ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755848

RESUMO

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

16.
J Inflamm Res ; 14: 5699-5711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754216

RESUMO

Background: Right heart failure is the terminal stage of PAH. When PAH patients suffer from pulmonary infection or puerperal infection heart failure often rapidly develops. Low dose of lipopolysaccharide induces rapid right ventricular failure in rats with pulmonary arterial hypertension. Purpose: The objective of this study was to investigate whether the NLRP3 inflammasome mediates disturbance of the ventricular immune microenvironment of PAH rats and promotes right ventricular failure. Methods: Intraperitoneal injection of monocrotaline was used to induce PAH in rats. Right ventricular function was measured via echocardiography before and after the rats were treated with lipopolysaccharide and MCC950. The degree of immune microenvironment disturbance in right ventricular tissue was measured with a rat chemokine and cytokine antibody array, Western blot, flow cytometry and quantitative real-time PCR analysis. Results: After the rats were injected with LPS, they exhibited right ventricular dysfunction and a significant increase in right ventricular tissue inflammation with elevated M1 macrophage proportion. Administration of MCC950 suppressed inflammation and improved right ventricular function. The number of M1 macrophages was decreased after MCC950 treatment. NLRP3 inflammasome inhibition ameliorated LPS-induced changes in the immune microenvironment in the right heart and right ventricular dysfunction in rats with PAH. Conclusion: Selective inhibition of NLRP3 pathway interfered the interaction between hypertrophic cardiomyocytes and macrophages in the initial stage of inflammation and maintained the immune microenvironment balance, eventually contributing to attenuation of LPS-induced acute heart failure in PAH rats.

17.
Front Neurosci ; 15: 648143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658751

RESUMO

Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD). Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children. Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group. Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.

18.
Int J Mol Sci ; 22(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34639167

RESUMO

Lung cancer is one of the most prevalent malignancies worldwide. Despite the undeniable progress in lung cancer research made over the past decade, it is still the leading cause of cancer-related deaths and continues to challenge scientists and researchers engaged in searching for therapeutics and drugs. The tumor microenvironment (TME) is recognized as one of the major hallmarks of epithelial cancers, including the majority of lung cancers, and is associated with tumorigenesis, progression, invasion, and metastasis. Targeting of the TME has received increasing attention in recent years. Natural products have historically made substantial contributions to pharmacotherapy, especially for cancer. In this review, we emphasize the role of the TME and summarize the experimental proof demonstrating the antitumor effects and underlying mechanisms of natural products that target the TME. We also review the effects of natural products used in combination with anticancer agents. Moreover, we highlight nanotechnology and other materials used to enhance the effects of natural products. Overall, our hope is that this review of these natural products will encourage more thoughts and ideas on therapeutic development to benefit lung cancer patients.


Assuntos
Antineoplásicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral/imunologia , Animais , Humanos , Neoplasias Pulmonares/imunologia , Microambiente Tumoral/efeitos dos fármacos
19.
Artigo em Inglês | MEDLINE | ID: mdl-34715346

RESUMO

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine, CoronaVac, remain elusive. METHODS: In a prospective cohort of 100 SARS-CoV-2 naïve healthcare professionals who received two doses of CoronaVac, we analyzed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks post the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells, and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 Spike-specific IgG responses reached the peak (geometric mean titer [GMT] 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2 specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2 specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac induced immune responses. SARS-CoV-2 memory CD4+ T cells was strongly associated with both RBD-specific memory B cells (r=0.87, p<0.0001) and SARS-CoV-2 specific memory CD8+ T cells (r=0.48, p<0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cells and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.

20.
Small ; : e2104241, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34713571

RESUMO

In this study, PtCu-Mo2 C heterostructure with charge redistribution is investigated via first-principles theoretical calculations. Mo2 C can promote the formation of the electron-rich region of PtCu as an active site, displaying an optimized adsorption behavior toward hydrogen in terms of reduced thermodynamic energy barriers. Owing to the attractive density functional theory calculation results, the PtCu-Mo2 C heterostructure is fabricated via carbonization of the unique metal-organic framework (MOF) followed by the replacement reduction reaction for the first time. Owing to its swift kinetics and outstanding specific activity, it exhibits high hydrogen evolution reaction (HER) catalytic activity (26 mV @ 10 mA cm-2 ) and superior mass activity (1 A mgPt -1 at -0.04 V) in acidic media, which is approximately six times that of commercial Pt/C catalysts. The perception of the intrinsic activity origin of the alloy with an excellent structural support can guide the development of Pt-based and other alloy catalysts in future.

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