Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 403
Filtrar
1.
Mol Cancer Res ; 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34610960

RESUMEN

Cancer stem cell (CSC) marker doublecortin-like kinase 1 (DCLK1) contributes greatly to the malignancy of gastrointestinal cancers, and DCLK1-targeted agents have potential therapeutic value. However, the molecular pathways regulated by DCLK1-S (DCLK1 isoform 4), a shortened splice variant of DCLK1, still remain obscure. Here we found that the expression of DCLK1-S is significantly increased in human esophageal squamous cell carcinoma (ESCC) tissues and associated with malignant progression and poor prognosis. Functional studies indicated that silencing total of DCLK1 mediated by CRISPR/Cas9 inhibited ESCC cell proliferation, migration, and invasion. Conversely, these changes were largely reversed after DCLK1-S rescue or overexpression. More importantly, DCLK1-S significantly enhanced primary tumor formation and metastatic lung colonization in vivo. TCGA (The Cancer Genome Atlas) database and molecular analysis showed that DCLK1-S was closely related to the epithelial-mesenchymal transition (EMT) process in ESCC patients. Further RNA-seq and KEGG analysis demonstrated that MAPK signaling pathway was significantly enriched. Our invitro study proclaimed that DCLK1-S induced MMP2 expression in ESCC cells via MAPK/ERK signaling, leading to the activation of EMT. Additionally, administration of ERK1/2 blocker SCH772984 attenuated the proliferative and migratory phenotype induced by DCLK1-S. In conclusion, these findings suggest that DCLK1-S may be a key molecule in MAPK/ERK/MMP2 pathway-mediated progression of ESCC, and that it has potential as a biomarker or therapeutic target to improve outcomes in ESCC patients. Implications: DCLK1-S induces ESCC progression by activating the MAPK/ERK/MMP2 axis and may serve as a prognostic biomarker or therapeutic target for ESCC patients.

2.
Artículo en Inglés | MEDLINE | ID: mdl-34689545

RESUMEN

Li-S batteries are considered to be the most promising next-generation advanced energy-storage systems. However, the sluggish reaction kinetics and the "shuttle effect" of lithium polysulfides (LiPSs) severely limit their battery performances. To overcome the complex and multiphase sulfur redox chemistry of LiPSs, in this study, we propose a new type of cobalt-based double catalytic sites (DCSs) codoped mesoporous carbon to immobilize and reversibly catalyze the LiPS intermediates in the cycling process, thus eliminating the shuttle effect and improving the charge-discharge kinetics. The theoretical calculation shows that the well-designed DCS configuration endows LiPSs with both strong and weak binding capabilities, which will facilitate the synergistic and reversible catalytic conversion. Furthermore, the experimental results also confirm that the DCS structure shows significantly enhanced catalytic kinetics than the single catalytic sites. The Li-S battery equipped with the DCS structure displays an extremely high discharge capacity of 918 mA h g-1 at a current density of 0.2 C and can reach a capacity of 867 mA h g-1 after 200 cycles with an ultralow capacity attenuation rate of 0.028% for each cycle. This study opens new avenues to address the catalytic requirements both in discharging and charging processes.

3.
Molecules ; 26(17)2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34500707

RESUMEN

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared. The micelle consisted of a zwitterionic segment as the hydrophilic shell and the drug Adriamycin (DOX) as the hydrophobic inner core. As a pH-responsive antitumor drug delivery system, the prodrug micelles showed high stability in a physiological environment and continuously released the drug under acidic conditions. In addition, the pure polyurethane carrier was demonstrated to be virtually non-cytotoxic by cytotoxicity studies, while the prodrug micelles were more efficient in killing tumor cells compared to PEG-PLGA@DOX. Furthermore, the DOX cellular uptake efficiency of prodrug micelles was proved to be obviously higher than the control group by both flow cytometry and fluorescence microscopy. This is mainly due to the modification of a zwitterionic segment with PU. The simple design of zwitterionic prodrug micelles provides a new strategy for designing novel antitumor drug delivery systems with enhanced cellular uptake rates.

4.
Cell Res ; 2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34561617

RESUMEN

Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system remodels has been poorly understood. Here we identify a new type of membrane contact formed between the ER-Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER-Golgi system, which is essential for promoting autophagosome biogenesis induced by different stress stimuli. The ERGIC-ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2-5 nm) between the two compartments. The tight membrane contact allows the ERES-located SEC12 to transactivate COPII assembly on the ERGIC. In addition, a portion of SEC12 also relocates to the ERGIC. Through both mechanisms, the ERGIC-ERES contact promotes formation of the ERGIC-derived COPII vesicle, a membrane precursor of the autophagosome. The ERGIC-ERES contact is physically and functionally different from the TFG-mediated ERGIC-ERES adjunction involved in secretory protein transport, and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.

5.
J Nucl Cardiol ; 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34476781

RESUMEN

BACKGROUND: Coronary microvascular dysfunction (CMD) may precede clinically overt coronary artery disease (CAD). Overall and central obesity (CO) are major risk factors for CAD. This study sought to investigate the subclinical significance of body adiposity patterns based on the CMD risk. METHODS: A total of 128 patients with non-obstructive CAD were prospectively enrolled. Patients were categorized into 4 anthropometric groups: normal weight and non-CO (NWNCO, n = 41), normal weight and CO (NWCO, n = 20), excess weight and non-CO (EWNCO, n = 26), and excess weight and CO (EWCO, n = 41). Patients underwent rest/stress electrocardiography-gated 13N-ammonia positron emission tomography to measure absolute myocardial blood flow (MBF), myocardial flow reserve (MFR), hemodynamic parameters, and cardiac function. RESULTS: Resting MBF did not differ between groups (P = .36). Compared with the NWNCO group, hyperemic MBF and MFR were significantly lower in the NWCO and EWCO groups. Notably, patients with NWCO presented the lowest hyperemic MBF and MFR and the highest incidence of CMD. Waist circumference was an independent risk factor for CMD (OR 1.05, 95% CI 1.01 to 1.10, P = .02). CONCLUSION: In patients with non-obstructive CAD, CO may be associated with an increased risk of CMD to better fit the study findings which did not assess management or monitoring of MBF and MFR.

6.
Health Qual Life Outcomes ; 19(1): 213, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488798

RESUMEN

BACKGROUND: Although physical activity (PA) and sedentary time in cancer survivors (CSs) were associated with health-related quality of life (HRQOL), it was not clear whether their associations were similar among CSs with different number of comorbid chronic diseases (CCDs). This study aimed to investigate the associations between PA, sedentary time and HRQOL in CSs with different number of CCDs. METHODS: A cross-sectional study was conducted among 1546 CSs between June and September 2018 in Shanghai, China. Data were collected with a self-reported questionnaire including sociodemographic characteristics, CCDs, PA, sedentary time and HRQOL. International Physical Activity Questionnaire and Cancer Quality of Life Questionnaire-Core30 were respectively used to measure PA and HRQOL of CSs. Associations of PA and sedentary time with HRQOL among CSs with different number of CCDs were evaluated by using logistic regression, adjusted for confounding factors. RESULTS: About seventy-five percent CSs had at least one CCD. Approximately three fifths CSs had high PA level and < 4 h/day sedentary time. Moderate PA level and high PA level were shown to be associated with better HRQOL among all participants. In CSs with ≤ 2 CCDs, high PA level was significantly associated with higher scores of physical function and lower scores of nausea and vomiting, appetite loss. However, there was a positive association between high PA level and constipation score among CSs with ≥ 3 CCDs. CSs with shorter sedentary time had better HRQOL in those with CCDs. CONCLUSIONS: High PA level and long sedentary time have significant association with worse HRQOL of CSs with ≥ 3 CCDs, while high PA level is positively associated with HRQOL in CSs with ≤ 2 CCDs. Our findings may support further studies of the causal association between PA, sedentary times and HRQOL to provide targeted proposal to improve the HRQOL of CSs according to their number of CCDs.


Asunto(s)
Supervivientes de Cáncer/psicología , Ejercicio Físico/fisiología , Neoplasias/mortalidad , Calidad de Vida/psicología , Conducta Sedentaria , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Ejercicio Físico/psicología , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Encuestas y Cuestionarios , Terapéutica
7.
ACS Appl Mater Interfaces ; 13(35): 41609-41618, 2021 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-34428013

RESUMEN

Engineering efficient zinc-air batteries have attracted tremendous attention because of their essential role in the field of renewable energy systems. However, the sluggish reaction kinetics of the oxygen reduction reaction (ORR) at the air cathode impair the battery performance significantly. Recently, metal-N-C-based porous carbon nanoarchitectures have emerged as promising ORR electrocatalysts in zinc-air batteries. Herein, taking advantage of metal-organic complexation and mesoporous silica templates, we successfully anchor Fe-N-C sites on hierarchically porous carbon sphere and carbon nanotube interpenetrated nanostructures (Fe-N-C/HPCS@CNT) to serve as efficient cathodes for zinc-air batteries. Benefiting from its synergistic effects between the highly active Fe-N-C sites, ultrahigh surface areas, and unique hierarchically porous nanostructures, Fe-N-C/HPCS@CNT exhibits preferable ORR performance (E1/2 = 0.873 V) compared to commercial Pt/C (E1/2 = 0.841 V). Most importantly, when used as a cathode catalyst for homemade zinc-air batteries, Fe-N-C/HPCS@CNT exhibits gratifying peak power density (164.0 mW cm-2), large specific capacity (762.0 mAh g-1), superior long-term stability, extraordinary rate capability, and excellent charge/discharge performance. We believe that this report will not only offer new insights into the design of Fe-N-C-based catalysts but also promote the practical utilization of Fe-N-C-based cathodes for a wide range of energy applications.

8.
Nanoscale Adv ; 3(4): 1019-1028, 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-34381959

RESUMEN

Chromatin is spatially organized in a hierarchical manner by virtue of single nucleosomes condensing into higher order chromatin structures, conferring various mechanical properties and biochemical signals. These higher order chromatin structures regulate genomic function by organization of the heterochromatin and euchromatin landscape. Less is known about its transition state from higher order heterochromatin to the lower order nucleosome form, and there is no information on its physical properties. We have developed a facile method of electron microscopy visualization to reveal the interphase chromatin in eukaryotic cells and its organization into hierarchical branching structures. We note that chromatin hierarchical branching can be distinguished at four levels, clearly indicating the stepwise transition from heterochromatin to euchromatin. The protein-DNA density across the chromatin fibers decreases during the transition from compacted heterochromatin to dispersed euchromatin. Moreover, the thickness of the chromatin ranges between 10 to 270 nm, and the controversial 30 nm chromatin fiber exists as a prominent intermediate structure. This study provides important insights into higher order chromatin organization which plays a key role in diseases such as cancer.

9.
J Clin Lab Anal ; : e23986, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34462984

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant carcinoma with high rate of mortality. The current treatment is ineffective with poor survival time. Therefore, there is an urgent need for effective therapeutic drug regimens. The multi-target tyrosine kinase inhibitor (TKI) anlotinib has been approved for treating non-small cell lung cancer (NSCLC); however, the combined therapeutic regimen of anlotinib for ICC has not been investigated yet. This study aims to investigate the inhibitory effect of anlotinib and the mechanism of gemcitabine combination for ICC treatment. METHODS: Two ICC cell lines, HCCC-9810 and RBE cells, were used in this study. Cell Counting Kit-8 (CCK-8) was used to study the cell viability, and flow cytometry (FCM) was used to evaluate the apoptosis and cell cycle arrest. Compusyn software was used to calculate the combination index (CI) of anlotinib and gemcitabine. The protein expression rate of cleaved PARP/PARP and cleaved caspase-3/caspase-3 was detected by Western blotting. RESULTS: Our result showed that the anlotinib and gemcitabine combination significantly inhibits the growth of ICC cell lines. Compusyn software results showed that the combination regimen had an anti-tumor synergistic effect. FCM results showed that it promoted apoptosis. Moreover, it increased the protein expression rate of cleaved PARP/PARP and cleaved caspase-3/caspase-3. Finally, we found a synergistic anti-tumor effect by increasing G0/G1 cell cycle arrest. CONCLUSION: The combination of anlotinib and gemcitabine can increase the anti-tumor effect and may be a potential therapeutic drug regimen in a clinical setting.

10.
Artículo en Inglés | MEDLINE | ID: mdl-34363725

RESUMEN

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

11.
J Viral Hepat ; 28(10): 1413-1421, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34310810

RESUMEN

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2 months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.


Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B , Femenino , Estudios de Seguimiento , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B , Vacunas contra Hepatitis B , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Madres , Estudios Prospectivos , Vacunación
12.
Math Biosci Eng ; 18(4): 4127-4145, 2021 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-34198429

RESUMEN

Radio frequency energy harvesting (EH) technology can harvest the electromagnetic energy in the surrounding environment, and reduce the dependence of the communication devices on battery or power grid as power source, which is a very promising means of energy substitution and acquisition scheme. The random characteristics of wireless channel fading and possible co-channel interference (CCI) have great influence on EH efficiency and wireless communication performance with more complicated theoretical analysis. In this paper, the exact closed-form expressions of effective throughput of "harvest-store-use" and "harvest-use" multi-slot EH schemes with Rayleigh channel fading and CCI are derived theoretically. The simulation results show that in Rayleigh fading channels with CCI, CCI is beneficial to energy harvesting of EH device, but it will deteriorate the reception of required signals by information receiving device. Although there are obvious differences in working mechanism, working conditions and communication performance between the "harvest-store-use" scheme and the "harvest-use" scheme, the optimal time slot should be selected to balance the transmission probability and delay, minimize the interference of CCI to the desired signal, and improve the energy conversion efficiency of the energy harvester.


Asunto(s)
Redes de Comunicación de Computadores , Tecnología Inalámbrica , Comunicación , Simulación por Computador , Probabilidad
13.
ACS Omega ; 6(27): 17173-17182, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34278104

RESUMEN

The fast deactivation caused by serious formation of coke is a major challenge in catalytic isomerization of endo-tetrahydrodicyclopentadiene (endo-THDCPD) into exo-tetrahydrodicyclopentadiene (exo-THDCPD) over the HY zeolite. In order to suppress the coke formation for the isomerization process, the conventional HY zeolite was modified with Pt at 0.3 wt %. Then, the hydroisomerization of endo-THDCPD into exo-THDCPD was evaluated over a fixed-bed reactor. The catalytic stability of Pt/HY was greatly enhanced in comparison to that of the HY zeolite. The Pt/HY catalyst provided 97% endo-THDCPD conversion and 96% selectivity for exo-THDCPD without deactivation after 100 h. Moreover, the formation mechanism of coke on the HY zeolite during the isomerization process was proposed based on the results of the coke analysis. It was indicated that the coke was generated from the oligomerization and condensation of olefin species, which originated from the ß-scission reaction or hydride transfer reaction of intermediates. The lower coke formation over Pt/HY was attributed to the lower amount of coke precursors, which could be hydrogenated by activated H2 over Pt sites. Therefore, Pt on Pt/HY and H2 were two crucial factors in efficiently enhancing the catalytic stability of the HY zeolite for this isomerization reaction.

14.
Neural Comput ; : 1-34, 2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34280263

RESUMEN

Learning new concepts rapidly from a few examples is an open issue in spike-based machine learning. This few-shot learning imposes substantial challenges to the current learning methodologies of spiking neuron networks (SNNs) due to the lack of task-related priori knowledge. The recent learning-to-learn (L2L) approach allows SNNs to acquire priori knowledge through example-level learning and task-level optimization. However, an existing L2L-based framework does not target the neural dynamics (i.e., neuronal and synaptic parameter changes) on different timescales. This diversity of temporal dynamics is an important attribute in spike-based learning, which facilitates the networks to rapidly acquire knowledge from very few examples and gradually integrate this knowledge. In this work, we consider the neural dynamics on various timescales and provide a multi-timescale optimization (MTSO) framework for SNNs. This framework introduces an adaptive-gated LSTM to accommodate two different timescales of neural dynamics: short-term learning and long-term evolution. Short-term learning is a fast knowledge acquisition process achieved by a novel surrogate gradient online learning (SGOL) algorithm, where the LSTM guides gradient updating of SNN on a short timescale through an adaptive learning rate and weight decay gating. The long-term evolution aims to slowly integrate acquired knowledge and form, which can be achieved by optimizing the LSTM guidance process to tune SNN parameters on a long timescale. Experimental results demonstrate that the collaborative optimization of multi-timescale neural dynamics can make SNNs achieve promising performance for the few-shot learning tasks.

15.
Stem Cell Res ; 54: 102397, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098200

RESUMEN

The 46, XX male sex reversal syndrome (SRS) is a rare disease with a gender dysplasia phenotype. Scientists concur that SRS is associated with translocation of the sex-determining region Y gene (SRY). We obtained peripheral blood mononuclear cells (PBMCs)from an 18-year-old male with SRS to generate an induced pluripotent stem cell (iPSC) line (SMUSHi001-A). Karyotyping analysis of the patient PBMCs revealed a normal 46, XX karyotype carrying the SRY gene. Pluripotent markers were successfully detected in SMUSHi001-A which can be differentiated into three germ layers in vitro. This cell line will provide a cell model for exploring the pathogenesis and potential therapeutic methods of SRS.


Asunto(s)
Trastornos Testiculares del Desarrollo Sexual 46, XX , Células Madre Pluripotentes Inducidas , Trastornos Testiculares del Desarrollo Sexual 46, XX/genética , Adolescente , Genes sry , Humanos , Cariotipificación , Leucocitos Mononucleares , Masculino
16.
Clin Pharmacol Drug Dev ; 10(8): 840-849, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34105265

RESUMEN

To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single-site, open-label, randomized, 2-preparation, single-dose, 2-period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%-100.20% for the area under the concentration-time curve (AUC) from time zero to the last measured concentration (AUC0-t ), 91.73%-100.14% for the AUC from administration to infinite time (AUC0-∞ ), and 98.52%-112.52% for the maximum plasma concentration (Cmax ). In the fed state, AUC0-t , AUC0-∞ , and Cmax were 92.23%-100.20%, 91.73%-100.14%, and 95.91%-105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%-125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax ) nor the terminal elimination half-life (t1/2 ) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.

17.
Free Radic Res ; 55(6): 720-730, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34160338

RESUMEN

Gastric cancer is a common lethal malignancy and causes great cancer-related mortality worldwide. MicroRNA (miR)-328-3p is implicated in the progression of various human cancers; however, its role and mechanism in the progression of gastric cancer remain unclear.Human gastric cancer cells were incubated with miR-328-3p mimic, inhibitor or the matched negative control. Cell viability, colony formation, migrative and invasive capacity, cell apoptosis and oxidative stress were measured. To clarify the involvement of nuclear factor-E2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1), small interfering RNA was used. miR-328-3p was upregulated in human gastric cancer cells and tissues, and its level positively correlated with the progression of gastric cancer. miR-328-3p promoted cell viability, colony formation, migration and invasion, thereby facilitating the progression of gastric cancer. miR-328-3p mimic reduced, while miR-328-3p inhibitor increased apoptosis and oxidative stress of human gastric cancer cells. Mechanistically, miR-328-3p upregulated NRF2 via targeting KEAP1to attenuate excessive free radical production and cell apoptosis. miR-328-3p functions as an oncogenic gene and inhibiting miR-328-3p may help to develop novel therapeutic strategies of human gastric cancer.

18.
PLoS Negl Trop Dis ; 15(6): e0009505, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34153039

RESUMEN

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy. METHODOLOGY/PRINCIPLE FINDINGS: We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%). CONCLUSIONS/SIGNIFICANCE: JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.


Asunto(s)
Costo de Enfermedad , Encefalitis Japonesa/economía , Costos de la Atención en Salud/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Virus de la Encefalitis Japonesa (Especie)/inmunología , Encefalitis Japonesa/epidemiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida
19.
Proc Natl Acad Sci U S A ; 118(24)2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34108240

RESUMEN

DNA replication is dramatically slowed down under replication stress. The regulation of replication speed is a conserved response in eukaryotes and, in fission yeast, requires the checkpoint kinases Rad3ATR and Cds1Chk2 However, the underlying mechanism of this checkpoint regulation remains unresolved. Here, we report that the Rad3ATR-Cds1Chk2 checkpoint directly targets the Cdc45-MCM-GINS (CMG) replicative helicase under replication stress. When replication forks stall, the Cds1Chk2 kinase directly phosphorylates Cdc45 on the S275, S322, and S397 residues, which significantly reduces CMG helicase activity. Furthermore, in cds1 Chk2 -mutated cells, the CMG helicase and DNA polymerases are physically separated, potentially disrupting replisomes and collapsing replication forks. This study demonstrates that the intra-S phase checkpoint directly regulates replication elongation, reduces CMG helicase processivity, prevents CMG helicase delinking from DNA polymerases, and therefore helps preserve the integrity of stalled replisomes and replication forks.

20.
Artículo en Inglés | MEDLINE | ID: mdl-34138718

RESUMEN

Group activity recognition (GAR) aiming at understanding the behavior of a group of people in a video clip has received increasing attention recently. Nevertheless, most of the existing solutions ignore that not all the persons contribute to the group activity of the scene equally. That is to say, the contribution from different individual behaviors to group activity is different; meanwhile, the contribution from people with different spatial positions is also different. To this end, we propose a novel Position-aware Participation-Contributed Temporal Dynamic Model (P²CTDM), in which two types of the key actor are constructed and learned. Specifically, we focus on the behaviors of key actors, who maintain steady motions (long moving time, called long motions) or display remarkable motions (but closely related to other people and the group activity, called flash motions) at a certain moment. For capturing long motions, we rank individual motions according to their intensity measured by stacking optical flows. For capturing flash motions that are closely related to other people, we design a position-aware interaction module (PIM) that simultaneously considers the feature similarity and position information. Beyond that, for capturing flash motions that are highly related to the group activity, we also present an aggregation long short-term memory (Agg-LSTM) to fuse the outputs from PIM by time-varying trainable attention factors. Four widely used benchmarks are adopted to evaluate the performance of the proposed P²CTDM compared to the state of the art.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...