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1.
Eur J Med Chem ; 227: 113922, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34700270

RESUMO

BRD4-targeted proteolysis targeting chimera (PROTAC) have exhibited promising in vitro and in vivo anticancer activity in a number of cancer models. However, the clinical development of current reported BRD4-PROTACs have stagnated, largely due to the safety risks caused by their poor degradation selectivity. In this study, we designed and synthesized a series of PROTACs based on our recently reported dual BET/PLK1 inhibitor WNY0824, which led to the discovery of an isoform-selective and potent BRD4-PROTAC 12a (WWL0245). WWL0245 exhibited excellent selective cytotoxicity in the BETi sensitive cancer cell lines, including AR-positive prostate cancer cell lines. It could also efficiently induce ubiquitin-proteasomal degradation of BRD4 in AR-positive prostate cancer cell lines, with sub-nanomolar half-maximal degrading concentration (DC50) and maximum degradation (Dmax) > 99%. Moreover, WWL0245 induced cell cycle arrest at the G0/G1 phase and apoptosis in AR-positive prostate cancer by downregulation of the protein levels of AR, PSA and c-Myc as well as transcriptionally suppressed AR-regulated genes. WWL0245 was thus expected to be developed as a promising drug candidate for AR-positive prostate cancer and a valuable tool compound to study the biological function of BRD4.

2.
Stem Cells Transl Med ; 10 Suppl 2: S10-S17, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34724715

RESUMO

Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy. However, due to the nature of utilizing autologous T cells, affordability and availability are major hurdles, in addition to scientific challenges relating to CAR-T therapy optimization. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization. CAR-NK cells do not cause graft vs host disease and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics readily available for patients. Furthermore, unlike cytotoxic T cells, NK cells specifically target and eliminate cancer stem cells, which are the cells causing relapse and metastasis. PSCs can be genetically manipulated and engineered with CARs at the pluripotent stage, which allows the establishment of permanent, stable, and clonal PSC-CAR lines for the manufacture of unlimited homogenous CAR-NK cells. Multiple master PSC-CAR cell banks targeting a variety of antigens for cancer, viral infection, and autoimmune diseases provide inexhaustible cell sources for all patients. Development of a next-generation 3D bioreactor platform for PSC expansion and NK cell production overcomes major barriers related to cost and scalability for CAR-NK product.

3.
Nanoscale ; 13(45): 19085-19097, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34761764

RESUMO

Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO2 nanozyme on the surface (PPy@BSA-MnO2) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO2 undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn2+. Then, Mn2+ can convert H2O2 into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) T1-weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, PPy@BSA-MnO2 nanoprobes have excellent in vitro 4T1 cell-killing effect and in vivo tumor-suppressive properties. The acute toxicity assessment results indicate that PPy@BSA-MnO2 nanoprobes have good biological safety. Therefore, the as-prepared multifunctional PPy@BSA-MnO2 nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.


Assuntos
Neoplasias , Polímeros , Animais , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Camundongos , Óxidos , Pirróis , Nanomedicina Teranóstica
4.
Ann Palliat Med ; 10(10): 10527-10534, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763499

RESUMO

BACKGROUND: Laparoscopic pyeloplasty (LP) has been widely used to treat ureteropelvic junction obstruction (UPJO); however, no previous series of reports has focused on analyzing the factors that influence the complications and outcomes of LP. In this study, we analyzed the risk factors related to complications of LP, especially that of restenosis. The aim of this study is to perform meta-analysis of relevant comparative studies to analyze the risk factors of restenosis after LP treatment with ureteral stent as of 30 April 2021. METHODS: A systematic search was conducted in April 2021. The evaluation results included operation time (OT), intraoperative blood loss (IBL), anastomotic tension (AT), postoperative drainage (PD), and ectopic blood vessels (EBV). Relative risk (RR) and standardized mean difference (SMD) were extrapolated with a 95% confidence interval (CI). Subgroup analysis was performed based on research design and technology. RESULTS: After screening, 7 studies were included, incorporating a total of 979 patients with PUJO treated by LP. Analysis revealed the likelihood of risk factors as follows: OT [mean difference (MD) -3.16, 95% CI: -7.18 to 0.85; P=0.12], IBL (MD -3.16, 95% CI: -7.18 to 0.85; P=0.12), AT (RR 3.86, 95% CI: 2.96 to 5.02; P<0.00001), PD (MD 303.97, 95% CI: 219.49 to 388.44; P<0.00001), and EBV (RR 1.15, 95% CI: 0.78 to 1.68; P=0.49). The results indicated that high AT and increased PD are risk factors for postoperative ureteral restenosis. DISCUSSION: The results of the meta-analysis showed that among the factors related to the efficacy of LP in the treatment of ureteral stenosis, OT, IBL, AT, and EBV were not significantly correlated with postoperative restenosis. However, AT and PD are independent risk factors for postoperative restenosis of the ureter. Therefore, during the operation, the AT should be reduced, and the local injury is reduced to reduce the PD, thereby reducing the risk of restenosis.


Assuntos
Laparoscopia , Ureter , Obstrução Ureteral , Constrição Patológica , Humanos , Pelve Renal , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Resultado do Tratamento , Ureter/cirurgia , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos
5.
Artigo em Inglês | MEDLINE | ID: mdl-34822332

RESUMO

Due to the high price of the product and the limitation of laboratory conditions, reliability tests often get a small number of failed samples. If the data are not handled properly, the reliability evaluation results will incur grave errors. In order to solve this problem, this work proposes an artificial intelligence (AI) enhanced reliability assessment methodology by combining Bayesian neural networks (BNNs) and differential evolution (DE) algorithms. First, a single hidden layer BNN model is constructed by fusing small samples and prior information to obtain the 95% confidence interval (CI) of the posterior distribution. Then, the DE algorithm is used to iteratively generate optimal virtual samples based on the 95% CI and small samples trends. A reliability assessment model is reconstructed based on double hidden layers BNN model by combining virtual samples and test samples in the last stage. In order to verify the effectiveness of the proposed method, an accelerated life test (ALT) of the subsurface electronic control unit (S-ECU) was carried out. The verification test results show that the proposed method can accurately evaluate the reliability life of a product. And compared with the two existing methods, the results show that this method can effectively improve the accuracy of the reliability assessment of a test product.

6.
Molecules ; 26(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34833893

RESUMO

Dietary fiber is a widely recognized nutrient for human health. Previous studies proved that dietary fiber has significant implications for gastrointestinal health by regulating the gut microbiota. Moreover, mechanistic research showed that the physiological functions of different dietary fibers depend to a great extent on their physicochemical characteristics, one of which is solubility. Compared with insoluble dietary fiber, soluble dietary fiber can be easily accessed and metabolized by fiber-degrading microorganisms in the intestine and produce a series of beneficial and functional metabolites. In this review, we outlined the structures, characteristics, and physiological functions of soluble dietary fibers as important nutrients. We particularly focused on the effects of soluble dietary fiber on human health via regulating the gut microbiota and reviewed their effects on dietary and clinical interventions.

7.
Front Cell Infect Microbiol ; 11: 708088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692558

RESUMO

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.


Assuntos
Doenças das Artérias Carótidas , Microbioma Gastrointestinal , Biomarcadores , Clostridiales , Humanos , Metaboloma , Metabolômica
8.
Front Nutr ; 8: 743492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660667

RESUMO

Chitosan oligosaccharides (COS) play a prebiotic role in many ways, whereas its function on microbiota is not fully understood. In this study, the effects of COS on metabolic syndrome were initially investigated by testing changes in the physiological indicators after adding COS to the diet of mice with high fat (group H) and low fat (group L). The results showed that COS markedly inhibited the accumulation of body weight and liver fat induced by high-fat diet, as well as restored the elevated concentration of blood glucose and fasting insulin to normal levels. Next, changes of the murine intestinal microbiota were examined. The results exhibited that COS reduced with-in-sample diversity, while the between-sample microbial diversity enhanced. Specifically, COS enriched Clostridium paraputrificum and Clostridium ramosum in the mice on a high-fat diet, while the abundance of Clostridium cocleatum was reduced. As a comparison, Parabacteroides goldsteinii and Bacteroides uniformis increased their abundance in response to COS in the low-fat diet group. Noticeably, a large amount of Akkermansia muciniphila was enriched in both high-fat or low-fat diet groups. Among the differential fecal bacteria, Clostridium ramosume was found to be positively interacted with Faecalibacterim prausnitzii and Clostridium paraputrificum; Clostridium paraputrificum had a positive interactions with Lactococcus chungangensis and Bifidobacterium mongoliense, suggesting that COS probably ameliorate metabolic syndrome through the microbiota in view of the lipid-lowering effects of these interacted bacteria. Furthermore, the gene expression data revealed that COS improved the functions related to intestinal barrier and glucose transport, which could be the trigger and consequence of the variations in gut microbiota induced by COS. Additionally, correlation analysis found that intestinal bacteria are related to physiological parameters, which further supports the mediating role of gut microbiota in the beneficial effect of COS. In summary, our research results provide new evidence for the prebiotic effects of COS.

9.
Cell Death Discov ; 7(1): 294, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650058

RESUMO

A remarkable shift in Mesenchymal stromal cells (MSCs) plays an important role in cancer metastasis, but the molecular mechanism is still unclear. CPNE7, a calcium-dependent phospholipid-binding protein, mediates signal transduction and metastasis in many tumours. Here, we demonstrated that MSCs derived from OSCC (OSCC-MSCs) promoted the metastasis of OSCC cells by transwell assay and animal models through epithelial to mesenchymal transition (EMT) (p < 0.05). RNA-sequencing, ELISA, neutralizing antibody and CXCR2 inhibitor assay confirmed that CXCL8 secreted by OSCC-MSCs was associated with the upregulated expression of CPNE7 by immunohistochemical and western blotting (p < 0.05). This is mechanistically linked to the activation of CPNE7 to NF-κB pathway-induced metastasis, including phosphorylated p65 and IκBa. CPNE7 silencing inhibited metastatic abilities and the expression of CXCL8, phosphorylated p65, IκBa, and p65 nuclear translocation by western blotting and immunofluorescence, while CPNE7 overexpression markedly promoted these events (p < 0.05). We also identified that Nucleolin could be bind CPNE7 and IκBa by co-immunoprecipitation. Together, our results suggest that upregulation of CPNE7 in MSCs interacted with surface receptor -Nucleolin and then combined with IκBa to promoted phosphorylated IκBa and p65 nuclear translocation to active NF-κB pathway, and then regulates CXCL8 secretion to promote the metastasis of OSCC cells. Therefore, CPNE7 in MSCs could be promising therapeutic targets in OSCC.

10.
PLoS One ; 16(10): e0258763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710171

RESUMO

OBJECTIVES: This study aimed to identify the 15-year trends of handgrip strength-to-weight (relative HS) and assess the association between relative HS and hypertension among Chinese adults aged 20-69. METHODS: Using a complex, stratified, multistage probability cluster sampling, we analyzed data collected from 712,442 adults aged 20-69 years in four successive national surveys (2000-2014). We used a handheld dynamometer to measure strength and divided by body weight to calculate the relative HS. Blood pressure was recorded with a sphygmomanometer and hypertension was defined as resting systolic blood pressure at least 140 mmHg or diastolic at least 90 mmHg. The Mann-Kendall trend test examined trends in relative HS over time. We also computed odd ratios (OR) and 95% confidence intervals (95% CI) by tertile of relative HS and examined the association between relative HS and hypertension. RESULTS: The relative HS level decreased with the increase of age in both male and females (p trend <0.001). In each of four surveys, one interquartile decrease in relative HS was associated with an increased risk of hypertension by 44% (OR = 1.44, 95%CI: 1.40-1.47), 58% (OR = 1.58, 95%CI: 1.54-1.62), 48% (OR = 1.48, 95%CI: 1.45-1.52), 43% (OR = 1.43, 95%CI: 1.40-1.47), respectively. CONCLUSION: In the Chinese adult population, the relative HS level decreased from 2000 to 2014 across all ages in both males and females. A lower relative HS was associated with a higher risk of hypertension. The findings provided evidence for the association between muscle strength and hypertension in large-scaled population.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Força da Mão , Hipertensão/epidemiologia , Força Muscular , Adulto , Idoso , Pressão Sanguínea , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
11.
World J Surg Oncol ; 19(1): 253, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446046

RESUMO

BACKGROUND: The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. METHODS: Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. RESULTS: A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3-4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15-4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06-4.17, P = 0.047). CONCLUSION: CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Taxa de Sobrevida
12.
Anticancer Drugs ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34338241

RESUMO

Activatable cell-penetrating peptide (ACPP) is a tumour-targeting cell-penetrating peptide. Here, we used ACPP to carry anti-p21Ras scFv for Ras-driven cancer therapy. The ACPP-p21Ras scFv fusion protein was prepared by a prokaryotic expression system and Ni-NTA column purification. The human tumour cell lines A549, SW480, U251 and Huh7 and the normal cell line BEAS 2B were used to study the tumor-targeting and membrane-penetrating ability of ACPP-p21Ras scFv. The antitumour activity of ACPP-p21Ras scFv on A549 cells and H1299 cells in vitro was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, scratch wound healing, plate cloning and apoptosis assays. The penetration pathway of ACPP was determined by enhanced green fluorescent protein. The ACPP-p21Ras scFv fusion protein was successfully obtained at a concentration of 1.8 mg/ml. We found that ACPP-p21Ras scFv could penetrate tumour cell membranes with high expression of matrix metalloproteinase-2 (MMP-2), effectively inhibit the migration and proliferation of A549 cells and H1299 cells, and promote the apoptosis of A549 cells and H1299 cells. The membrane penetration experiment demonstrated that ACPP could enter A549 cells by direct penetration. The ability of ACPP to penetrate the membrane was affected by the addition of a membrane affinity inhibitor and a change in the potential difference across the cell membrane but not by the addition of endocytosis inhibitors and a change in temperature. The ACPP-p21Ras scFv fusion protein can penetrate tumour cells with MMP-2 expression and has antitumour activity against A549 cells and H1299 cells in vitro. This molecule is expected to become a potential antitumour drug for Ras gene-driven lung cancer.

13.
Transl Vis Sci Technol ; 10(9): 6, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34347033

RESUMO

Purpose: Retinitis pigmentosa (RP) is caused by mutations in more than 60 genes. Mutation-independent approaches to its treatment by exogeneous administration of neurotrophic factors that will preserve existing retinal anatomy and visual function are a rational strategy. Ciliary neurotrophic factor (CNTF) and oncostatin M (OSM) are two potent survival factors for neurons. However, growth factors degrade rapidly if administered directly. A sustained delivery of growth factors is required for translating their potential therapeutic benefit into patients. Methods: Stable and biocompatible nanoparticles (NP) that incorporated with CNTF and OSM (CNTF- and OSM-NP) were formulated. Both NP-trophic factors were tested in vitro using photoreceptor progenitor cells (PPC) and retinal ganglion progenitor cells (RGPC) derived from induced pluripotent stem cells and in vivo using an optic nerve crush model for glaucoma and the Royal College of Surgeons rat, model of RP (n = 8/treatment) by intravitreal delivery. Efficacy was evaluated by electroretinography and optokinetic response. Retinal histology and a whole mount analysis were performed at the end of experiments. Results: Significant prosurvival and pro-proliferation effects of both complexes were observed in both photoreceptor progenitor cells and RGPC in vitro. Importantly, significant RGC survival and preservation of vision and photoreceptors in both complex-treated animals were observed compared with control groups. Conclusions: These results demonstrate that NP-trophic factors are neuroprotective both in vitro and in vivo. A single intravitreal delivery of both NP-trophic factors offered neuroprotection in animal models of retinal degeneration. Translational Relevance: Sustained nanoparticle delivery of neurotrophic factors may offer beneficial effects in slowing down progressive retinal degenerative conditions, including retinitis pigmentosa, age-related macular degeneration, and glaucoma.


Assuntos
Nanopartículas , Degeneração Retiniana , Animais , Fator Neurotrófico Ciliar , Humanos , Oncostatina M , Ratos , Degeneração Retiniana/tratamento farmacológico , Células Ganglionares da Retina , Roedores
14.
Artigo em Inglês | MEDLINE | ID: mdl-34333232

RESUMO

Ovarian development is a complex physiological process for crustacean reproduction that is divided into the oogonium proliferation stage, endogenous vitellogenic stage, exogenous vitellogenic stage, and oocyte maturation stage. Proteomics analysis offers a feasible approach to reveal the proteins involved in the complex physiological processes of any organism. Therefore, this study performed a comparative proteomics analysis of the ovary and hepatopancreas at three key ovarian stages, including stages I (oogonium proliferation), II (endogenous vitellogenesis) and IV (exogenous vitellogenesis), of the Chinese mitten crab Eriocheir sinensis using a label-free quantitative approach. The results showed that a total of 2,224 proteins were identified, and some key proteins related to ovarian development and nutrition metabolism were differentially expressed. The 26 key proteins were mainly involved in the ubiquitin/proteasome pathway (UPP), cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway during oogenesis. Fifteen differentially abundant proteins (DAPs) were found to participate in vitellogenesis and oocyte development, such as vitelline membrane outer layer protein 1 homolog, vitellogenin, vitellogenin receptor, heat shock 70 kDa protein cognate 3 and farnesyl pyrophosphate synthase. Forty-seven DAPs related to nutrition metabolism were identified, including the protein digestion, fatty acid metabolism, prostaglandin metabolism, lipid digestion and transportation, i.e. short-chain specific acyl-CoA dehydrogenase, acyl-CoA desaturase, fatty acid-binding protein, long-chain fatty acid CoA ligase 4, and hematopoietic prostaglandin D synthase. These results not only indicate proteins involved in ovarian development and nutrient deposition but also enhance the understanding of the regulatory pathways and physiological processes of crustacean ovarian development.

15.
PLoS One ; 16(8): e0256258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411164

RESUMO

BACKGROUND: Cardiorespiratory fitness (CRF) is the core element of health-related physical fitness evaluation. High pressure and low oxygen in Tibet (over 3,500 m above sea level) may negatively impact the residents' CRF. The 20-m shuttle run test (20mSRT) is the most popular field-based assessment and estimate of CRF in children and adolescents worldwide. However, normative CRF data for the children and adolescents residing in China's plateau region are unavailable, which prevents comparability among those living at high-altitudes around the world. PURPOSE: To measure the CRF of Chinese children and adolescents aged 9-18 years living in Tibet at altitudes exceeding 3,500 m, and to identify correlations between this metric and demographic characteristics (age, sex, and ethnicity). These data were then compared with those generated in the lowland (Shanghai, China) and various global regions. METHODS: 20mSRT performance (number of completed laps) and predicted peak oxygen consumption (VO2peak) were used as indicators of CRF. We measured the CRF of 1,717 healthy children and adolescents aged 9-18 years living in Tibet. The CRF data from school-age subjects in Shanghai (2,437 boys and 2,396 girls) and worldwide (1,142,026 students from 50 countries/regions in Africa, Asia, Europe, Latin America, North America, and Oceania) were collated from published papers. RESULTS: The average CRF of the participants from Tibet was 39.8 mL/kg/min. The male subjects (n = 876; 41.1 ± 4.42 mL/kg/min) had a higher average CRF than their female counterparts (n = 841; 37.8 ± 5.40 mL/kg/min). CRF decreased with age in both sexes at statistical significance (F = 1249.9, p for trend 0.05). The indigenous Tibetans (n = 1289; 40.1 ± 3.71 mL/kg/min) had a significant higher average CRF than those of Han descent (n = 394; 38.9 ± 4.70 mL/kg/min) (p < 0.05). CONCLUSIONS: Children and adolescents aged 7-18 years residing above 3,500 m in Tibet displayed lower CRF traits compared with their counterparts from the plains area and other high altitude places. CRF varied according to age, sex, and ethnic group. Given the importance of CRF in children and adolescents, effective intervention strategies should be implemented to improve CRF in children and adolescents on the plateau.

16.
J Clin Med ; 10(14)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34300234

RESUMO

PURPOSE: To investigate the changes in Chinese adults' physical activity (PA) behavior and determinants before and during the COVID-19 pandemic. METHOD: A total of 1028 adults (aged 19-59 years) were recruited from 127 urban and rural neighborhoods in China using stratified three-stage probability sampling. Data collection was conducted in December 2019 and July 2020. RESULTS: Compared with the data before the pandemic, individuals' weekly moderate-to-vigorous-intensity PA (MVPA) decreased significantly from 139 min to 120 min, seven months after the outbreak (p = 0.01), with female and rural populations displaying a more significant decrease (p = 0.02). Overall, 13.7% of participants met the PA guidelines (World Health Organization) both before and during the pandemic, while 21.8% met the guidelines only before the pandemic and 18.1% increased their PA and met the PA guidelines during the pandemic. A total of 46.4% did not meet the PA guidelines before or during the pandemic. Determinants of PA behavior change before and during the pandemic included sports skills, self-determined motivation and support from sports organizations. CONCLUSIONS: The Chinese adults' PA levels decreased significantly from before to during the COVID-19 pandemic, particularly among the female population. It is suggested that the enhancement of self-determined motivation, improvement of sport skills, and support from sports organizations might be effective in facilitating individuals' engagement in PA during the pandemic.

17.
Toxics ; 9(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202612

RESUMO

Sewage sludge and livestock (chicken, swine and cattle) manure samples were collected from the Yanmenguan Cattle Herbivorous Livestock Area to compare the potential ecological and human health risks caused by heavy metals contained in them. In this study, the Class II level of Quality Control of Imported Organic Fertilizers is selected as the limit standard value of heavy metals. Based on the mean content values, no heavy metal in cattle manure was higher than the limit standard value; the content of Cu in swine manure was higher than the limit of Cu; the content of Zn in sewage sludge, chicken manure and swine manure were all higher than the limit of Zn; and the content of Cr in sewage sludge and chicken manure were all higher than the limit of Cr. Results indicated that sewage sludge and livestock manure all had high contents of Zn, Cu and Cr. The mean pollution index (PI) suggested that Cu, Zn, As and Cr in sewage sludge and livestock manures all induced potential ecological risks. According to the mean Nemerow's synthetic pollution index (PN) values, swine manure had the highest potential ecological risk for agricultural use. Daily exposure to Cu, Zn and Cr was higher than other heavy metals from sewage sludge and livestock manures, and heavy metal exposure was always higher for children than adults, with ingestion as the main pathway. Non-carcinogenic risk was caused mainly by Cu and Cr, based on the higher hazard quotient (HQ) values for adults and children. There was no non-carcinogenic risk for all people, except exposure of Cu from swine manure for children, which was 1.76 times higher than the threshold value of 1. According to the mean hazard index (HI) values, only swine manure had a non-carcinogenic risk for children. As the carcinogenic risk index (Risk) values were continuously greater for As than Cd, As had a higher carcinogenic risk than Cd. There was no carcinogenic risk for any single heavy metal, although As exposure from sewage sludge was found to have an inapparent carcinogenic risk for both adults and children. Regarding the RISK value, sewage sludge had an unacceptable carcinogenic risk for adults and children, and swine manure had an unacceptable risk for children only. In general, for both non-carcinogenic and carcinogenic risks, ingestion was the main pathway, and children were more sensitive than adults. Comparing the four kinds of organic waste, cattle manure was the safest for agricultural use in terms of ecological and human health risks. In multiple comparisons, swine manure was significantly different regarding potential ecological risk and non-carcinogenic risk, and sewage sludge was significantly different regarding carcinogenic risk.

18.
Adv Mater ; 33(37): e2102054, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34309925

RESUMO

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with ß-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

19.
ACS Appl Mater Interfaces ; 13(24): 28415-28423, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34120440

RESUMO

Passivating contacts that simultaneously promote carrier selectivity and suppress surface recombination are considered as a promising trend in the crystalline silicon (c-Si) photovoltaic industry. In this work, efficient p-type c-Si (p-Si) solar cells with cuprous oxide (Cu2O) hole-selective contacts are demonstrated. The direct p-Si/Cu2O contact leads to a substoichiometric SiOx interlayer and diffusion of Cu into the silicon substrate, which would generate a deep-level impurity behaving as carrier recombination centers. An Al2O3 layer is subsequently employed at the p-Si/Cu2O interface, which not only serves as a passivating and tunneling layer but also suppresses the redox reaction and Cu diffusion at the Si/Cu2O interface. In conjunction with the high work function of Au and the superior optical property of Ag, a power conversion efficiency up to 19.71% is achieved with a p-Si/Al2O3/Cu2O/Au/Ag rear contact. This work provides a strategy for reducing interfacial defects and lowering energy barrier height in passivating contact solar cells.

20.
Environ Sci Pollut Res Int ; 28(40): 57334-57347, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34091849

RESUMO

Vehicle industry has made great contribution to human progress. However, in the process of vehicle operation, a large number of carbon compounds are emitted, which brings serious environmental problems. As one of the important means of vehicle carbon emission governance, the development of new energy vehicles (NEVs) has attracted much attention. The behavior and performance of NEV enterprises are highly concerned. Using Chinese 23 NEV vehicle enterprises' data from 2011 to 2018, this paper evaluates the carbon emission performance with the super-efficiency slacks-based measure (SE-SBM) model based on undesirable output and then constructs STIRPAT model to analyze the influencing factors of carbon emission performance. The results indicate that, firstly, the carbon emission performance of China's NEV enterprises is increasing year by year. Secondly, the carbon emission performance of different NEV enterprise is distinct in the same year, and the carbon emission performance of the same NEV enterprise is distinct in different year. Thirdly, technological innovation, government support, and free cash flow have significant positive impact on the carbon emission performance of NEV enterprises, while debt constraint, energy intensity, and enterprise size have a significant negative impact on the carbon emission performance of NEV enterprises.


Assuntos
Carbono , Desenvolvimento Econômico , Carbono/análise , China , Eficiência , Humanos , Indústrias
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