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1.
Clin Cancer Res ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879459

RESUMO

PURPOSE: Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency. EXPERIMENTAL DESIGN: Global phosphoproteomics, screening of a chemical library of FDA drugs and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRAS dependency. RESULTS: Global phosphoproteomics revealed that KRas dependency is driven by a cyclin dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identified AT7519, a CDK 1, 2, 7, and 9 inhibitor, as a potent inducer of apoptosis in mt KRas-dependent, but not in mt KRas-independent, human cancer cells. In vivo AT7519 inhibited the phosphorylation of CDK1, 2, 7 and 9 substrates and suppressed growth of xenografts from 5 pancreatic cancer patients. AT7519 also abrogated mt KRas and mt p53 primary and metastatic pancreatic cancer in 3D organoids from 2 patients, 3D co-cultures from 8 patients, and mouse 3D organoids from PanIN, primary and metastatic tumors. CONCLUSION: A link between CDK hyperactivation and mt KRas dependency was uncovered and pharmacologically-exploited to abrogate mt KRas-driven pancreatic cancer in highly relevant models, warranting clinical investigations of AT7519 in pancreatic cancer patients.

2.
Mol Metab ; 51: 101230, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823318

RESUMO

OBJECTIVE: Adaptive rewiring of cancer energy metabolism has received increasing attention. By binding with LDLs, LDLRs make most of the circulating cholesterol available for cells to utilize. However, it remains unclear how LDLR works in HCC development by affecting cholesterol metabolism. METHODS: Database analyses and immunohistochemical staining were used to identify the clinical significance of LDLR in HCC. A transcriptome analysis was used to reveal the mechanism of LDLR aberration in HCC progression. A liver orthotopic transplantation model was used to evaluate the role of LDLR in HCC progression in vivo. RESULTS: Downregulation of LDLR was identified as a negative prognostic factor in human HCC. Reduced expression of LDLR in HCC cell lines impaired LDL uptake but promoted proliferation and metastasis in vitro and in vivo. Mechanistically, increasing intracellular de novo cholesterol biosynthesis was the chief contributor to malignant behaviors caused by LDLR inhibition, which could be rescued by simvastatin. Activation of the MEK/ERK pathway by LDLR downregulation partially contributed to intracellular cholesterol synthesis in HCC. CONCLUSIONS: Downregulation of LDLR may elevate intracellular cholesterol synthesis to accelerate proliferation and motility through a mechanism partially attributed to stimulation of the MEK/ERK signaling pathway. Repression of intracellular cholesterol synthesis with statins may constitute a targetable liability in the context of lower LDLR expression in HCC.

3.
Am J Clin Dermatol ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33913115

RESUMO

BACKGROUND: Psoriasis is associated with metabolic syndrome; however, the relationship of psoriasis severity with individual cardiometabolic risk factors is not clear. There is a reporting gap between the cardiometabolic risks among patients with psoriasis and what has been reported in the literature using US samples. OBJECTIVES: The objective of this study was to examine the disease burden of psoriasis and assess the associations of psoriasis severity and cardiometabolic risk factors in a nationally representative sample. METHODS: We conducted a cross-sectional study using the weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) 2007 through 2016. The NAMCS data were collected from US office-based physicians. Each physician was randomly assigned a specific week to report a sample of their cases. Patients were categorized as severe psoriasis if they were prescribed at least one systemic therapy. We used logistic regression models adjusting for potential confounders to estimate the associations of psoriasis severity with individual cardiometabolic factors. RESULTS: There were about 3.3 million office-based psoriasis visits per year with a mean age of 50 years, a female-to-male ratio of 1:1, and severe disease in 23%. We observed greater values of blood pressure, lipid profiles, and higher body mass index among patients with psoriasis, compared with patients without psoriasis. A higher proportion of the psoriasis patient group were overweight and obese (73.6% vs 62.9% in the non-psoriasis patient group). Compared to mild case groups, severe case groups tended to have a higher proportion of overweight/obese with a body mass index ≥  25 kg/m2 (77% vs 73%). Obesity was weakly associated with psoriasis severity (adjusted odds ratio = 1.37, 95% confidence interval 0.98-1.91 for mild disease and adjusted odds ratio = 1.42, 95% confidence interval 0.80-2.52 for severe cases). CONCLUSIONS: Cardiometabolic factors are related health issues in psoriasis, and obesity is associated with greater psoriasis severity.

4.
Am J Hypertens ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864360

RESUMO

BACKGROUND: Many hospitalized patients with acute elevations in blood pressure are treated with intravenous (IV) antihypertensive medications without evidence of benefit. This study investigated the effects of IV as-needed (PRN) antihypertensives on blood pressure, hospital length of stay, and mortality. METHODS: We included hospitalized patients with an order for an IV PRN antihypertensive medication. We excluded patients with target organ damage. We performed multivariate analysis to assess whether the medication was independently associated with outcomes. RESULTS: 1784 out of 5680 patients (31%) had an administration of the PRN medication. Patients who received the medication had a longer hospital stay compared to patients with an order for the medication who did not receive it (4.9 ± 6.1 vs. 3.1 ± 4.1 days, p <0.001). This remained statistically significant after adjusting for covariates. In-hospital mortality was higher in the group that received the medication (3.3 vs. 1.6%, p <0.001), but this was not statistically significant on multivariate analysis. Intravenous hydralazine caused the most significant reduction in blood pressure and led to a shorter length of stay when compared to enalapril and labetalol. A total of 62% of patients received the medication for a systolic blood pressure lower than 180 mmHg. CONCLUSION: Treating hypertension in the in-patient setting remains complex. Rapid lowering of blood pressure can cause harm to patients, and this study showed that antihypertensive medication increased hospital length of stay. Once assuring no target organ damage, a strategic approach should be to treat modifiable factors and gradually reduce blood pressure.

5.
J Am Chem Soc ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847495

RESUMO

Photocatalytic nitrogen fixation reaction can harvest the solar energy to convert the abundant but inert N2 into NH3. Here, utilizing metal-organic framework (MOF) membranes as the ideal assembly of nanoreactors to disperse and confine gold nanoparticles (AuNPs), we realize the direct plasmonic photocatalytic nitrogen fixation under ambient conditions. Upon visible irradiation, the hot electrons generated on the AuNPs can be directly injected into the N2 molecules adsorbed on Au surfaces. Such N2 molecules can be additionally activated by the strong but evanescently localized surface plasmon resonance field, resulting in a supralinear intensity dependence of the ammonia evolution rate with much higher apparent quantum efficiency and lower apparent activation energy under stronger irradiation. Moreover, the gas-permeable Au@MOF membranes, consisting of numerous interconnected nanoreactors, can ensure the dispersity and stability of AuNPs, further facilitate the mass transfer of N2 molecules and (hydrated) protons, and boost the plasmonic photocatalytic reactions at the designed gas-membrane-solution interface. As a result, an ammonia evolution rate of 18.9 mmol gAu-1 h-1 was achieved under visible light (>400 nm, 100 mW cm-2) with an apparent quantum efficiency of 1.54% at 520 nm.

6.
Mater Sci Eng C Mater Biol Appl ; 123: 111966, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33812594

RESUMO

Herein, we integrate cell-imprinted substrate (CIS) and allochroic-graphene oxide (AGO) for specific visualization sorting of hepatocellular carcinoma cells. The state-of-the-art-of detection method relies on the enzyme linked immunosorbent assay (ELISA)-like sandwich strategy with hierarchical recognition. The target tumor cells are first selectively captured by the CIS based on cell imprinted recognition, and then specifically labeled with AGO by boronate affinity recognition between boronic acid on AGO and cis-diols on the surface of target cells. The selectively recognition of CIS for target template cells is verified by cell function experiments. It is also worth mentioning that the AGO can specifically recognize target tumor cells under physiological pH, and then perform signal amplification and output through pH-triggered allochroism. The CIS linked AGO for cell assay (CIS-AGO-CA) is successfully used for visualization detection of human hepatocarcinoma HLE cells from hepatocyte suspension. When the hepatocyte suspension is spiked with 1.0 × 105 cells, the recoveries of CIS-AGO-CA are 80.67 ± 4.33% for target HLE cells, and only 12.00 ± 1.00% for non-target Hep3B cells. It is worth emphasizing that the CIS-AGO-CA process is antibody-free. Therefore, this novel ELISA-like sandwich strategy is high specificity, cost-efficient and easy-to-use, and exhibits great prospect in the visualization sorting of tumor subpopulation.

7.
J Phys Chem Lett ; 12(14): 3577-3585, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33819039

RESUMO

Super-liquid-repellent (SLR) surfaces based on surface micro/nanotextures are generally regarded as "non-wettable", though careful examination shows that residual microdroplets remain atop surface textures upon drop shedding-off. Despite its great importance, the origin of microscopic liquid residues remains poorly explored, and how to suppress residue formation is an open question. Herein, on the basis of high-speed microscopic imaging and numerical simulations, we resolve the fast formation dynamics of liquid residues on micropillared SLR surfaces and show that the competition of contact line receding on micropillars and the pinch-off of microcapillary bridges governs residue formation. The local receding angle can temporarily reduce to be drastically lower than the intrinsic one accompanying occurrence of accelerated contact line receding, inevitably leading to capillary bridge pinch-off and residue formation. We further show a liquid-like coating can delay capillary bridge pinch-off and reduce residue volume on SLR surfaces by more than 80% compared to those with conventional perfluoroalkylsilane coatings.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33851818

RESUMO

Single crystal wafers, such as silicon, are the fundamental carriers of advanced electronic devices. However, these wafers exhibit rigidity without mechanical flexibility, limiting their applications in flexible electronics. Here, we propose a new approach to fabricate 1.5 in. flexible functional zinc oxide (ZnO) single crystal wafers with high electron mobility (>100 cm2 V-1 s-1) and optical transparency (>80%) by a combination of thin-film deposition, a chemical solution method, and surficial treatment. The uniformity of the flexible single crystal wafers is examined by an advanced scanning X-ray diffraction technique and photoluminescence spectroscopy. The transport properties of ZnO flexible single crystal wafers retain their pristine states under various bending conditions, including cyclability and endurability. This approach demonstrates a breakthrough in the fabrication of the flexible single crystal wafers for future flexible optoelectronic applications.

9.
Nat Commun ; 12(1): 1384, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654077

RESUMO

Many genetic diseases are caused by single-nucleotide polymorphisms. Base editors can correct these mutations at single-nucleotide resolution, but until recently, only allowed for transition edits, addressing four out of twelve possible DNA base substitutions. Here, we develop a class of C:G to G:C Base Editors to create single-base genomic transversions in human cells. Our C:G to G:C Base Editors consist of a nickase-Cas9 fused to a cytidine deaminase and base excision repair proteins. Characterization of >30 base editor candidates reveal that they predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean 15.4% and up to 37% without selection). C:G to G:C Base Editors target cytidine in WCW, ACC or GCT sequence contexts and within a precise three-nucleotide window of the target protospacer. We further target genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of these base editors in interrogating and correcting human genetic diseases.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Reparo do DNA/genética , Edição de Genes , Células HEK293 , Humanos , Motivos de Nucleotídeos/genética
10.
Medicine (Baltimore) ; 100(6): e24564, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578552

RESUMO

BACKGROUND: Among discharged COVID-19 patients, the health-related quality of life is poor, and patients suffer from significant physical and psychological impairment. This study was designed to investigate the effects of Liuzijue exercise on the rehabilitation of COVID-19 patients. METHODS: Thirty three eligible patients with COVID-19 were enrolled in the study after discharge. All the participants practiced Liuzijue exercise once per day for 20 minutes over 4 weeks. Data were collected at baseline and the end of the intervention. Primary outcomes involved functional capacity and secondary outcomes involved quality of life. RESULTS: The maximal inspiratory pressure (MIP), peak inspiratory flow (PIF), and diaphragm movement in deep breathing (DM-DB) of patients increased significantly after 4 weeks of intervention. The dyspnea was also alleviated and exercise capacity was significantly improved. In terms of quality of life, physical functioning and role-physical scores were significantly increased. Moreover, Liuzijue could significantly alleviate the depression and anxiety status of the patients. CONCLUSION: Liuzijue exercise is a viable alternative home exercise program that produced better functional capacity and quality of life in discharged patients with COVID-19. These findings also showed the necessity of rehabilitation intervention for cured COVID-19 patients.


Assuntos
/reabilitação , Qigong/métodos , Adulto , /psicologia , Diafragma/fisiopatologia , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Mecânica Respiratória
11.
Cancer Biol Med ; 18(1): 256-270, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628599

RESUMO

Objective: Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC. Methods: In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called "NBNC-HCC") and patients positive for the above indices (called "HBV-HCC and HCV-HCC") were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy. Results: The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under the curve: 0.986 (95% confidence interval: 0.958-0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort. For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificity for early-stage HCC [area under the curve: 0.776 (0.712-0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stage HBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784-0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group. Conclusions: The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.

12.
Phys Chem Chem Phys ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533768

RESUMO

Vibrational spectra of the methyl groups in mono-methylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) monomers and their clusters were measured in three experimental set-ups to capture their complex spectral features as a result of bend/umbrella-stretch Fermi resonance (FR). Multiple bands were observed between 2800 and 3000 cm-1 corresponding to the methyl groups for MMA and DMA. On the other hand, the corresponding spectrum of TMA is relatively simple, exhibiting only four prominent bands in the same frequency window, even though TMA has a larger number of methyl groups. The discrete variable representation (DVR) based ab initio anharmonic algorithm with potential energy surface (PES) at CCSD/aug-cc-pVDZ quality is able to capture all the experimentally observed spectral features across all three amines, and the constructed vibrational Hamiltonian was used to analyze the couplings that give rise to the observed FR patterns. It was observed that the vibrational coupling among CH stretch modes on different methyl groups is weak (less than 2 cm-1) and stronger vibrational coupling is found to localize within a methyl group. In MMA and DMA, the complex feature between 2850 and 2950 cm-1 is a consequence of closely packed overtone states that gain intensities by mixing with the stretching modes. The simplification of the spectral pattern of TMA can be understood by the red-shift of the symmetric CH3 stretching modes by about 80 cm-1 relative to MMA, which causes the symmetric CH3 stretch to shift outside the FR window.

13.
Complement Ther Med ; 57: 102640, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33388390

RESUMO

BACKGROUND: Mindful walking (MW) interventions employ mindfulness training combined with physical activity. Wearable mobile devices have been increasingly used to measure outcomes of physical activity interventions. The purpose of this study was to understand MW participants' attitudes towards MW and the use of mobile devices in health promotion interventions, including barriers and facilitators of intervention engagement and adherence. Few qualitative studies have documented participant experience with these two types of interventions. METHOD: The pilot study involved a randomized MW intervention including 38 participants with self-reported inadequate physical activity. Half of them were randomized to receive MW intervention plus a FitBit device and the other received the FitBit device only. We used a qualitative thematic analysis of the narrative data collected through open-ended survey questions at three time points. Participants in the MW intervention were asked to describe their experiences with MW, while all participants were asked to describe their experience with wearing the FitBit to track their step counts. RESULTS: Participants reported a broad range of perceived benefits and challenges related to adopting the MW intervention and using the mobile device. Participants were generally willing to try to adopt the recommended MW practice and to see value of MW in increasing physical activity and improving overall health. Participants reported using a variety of additional device features beyond goal setting and step counts, indicating using the devices may have been effective in providing additional motivation for participants in meeting physical activity goals in both the control and intervention groups. While most of the feedback about MW (in the intervention group) and the device (all participants) was overwhelmingly positive, a minority of participants reported barriers such as lack of patience with meditation and discomfort with wearing the device. CONCLUSION: Most participants in the MW intervention see the health benefits of this program and most participants using the wearable physical activity tracking device reported the motivational benefits of this device. Issues with the MW intervention (e.g., lack of patience) and the wearable device (e.g., discomfort with wearing) need to be addressed in future interventions.

14.
Eur Radiol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389033

RESUMO

OBJECTIVES: Near-pure lung adenocarcinoma (ADC) subtypes demonstrate strong stratification of radiomic values, providing basic information for pathological subtyping. We sought to predict the presence of high-grade (micropapillary and solid) components in lung ADCs using quantitative image analysis with near-pure radiomic values. METHODS: Overall, 103 patients with lung ADCs of various histological subtypes were enrolled for 10-repetition, 3-fold cross-validation (cohort 1); 55 were enrolled for testing (cohort 2). Histogram and textural features on computed tomography (CT) images were assessed based on the "near-pure" pathological subtype data. Patch-wise high-grade likelihood prediction was performed for each voxel within the tumour region. The presence of high-grade components was then determined based on a volume percentage threshold of the high-grade likelihood area. To compare with quantitative approaches, consolidation/tumour (C/T) ratio was evaluated on CT images; we applied radiological invasiveness (C/T ratio > 0.5) for the prediction. RESULTS: In cohort 1, patch-wise prediction, combined model (C/T ratio and patch-wise prediction), whole-lesion-based prediction (using only the "near-pure"-based prediction model), and radiological invasiveness achieved a sensitivity and specificity of 88.00 ± 2.33% and 75.75 ± 2.82%, 90.00 ± 0.00%, and 77.12 ± 2.67%, 66.67% and 90.41%, and 90.00% and 45.21%, respectively. The sensitivity and specificity, respectively, for cohort 2 were 100.0% and 95.35% using patch-wise prediction, 100.0% and 95.35% using combined model, 75.00% and 95.35% using whole-lesion-based prediction, and 100.0% and 69.77% using radiological invasiveness. CONCLUSION: Using near-pure radiomic features and patch-wise image analysis demonstrated high levels of sensitivity and moderate levels of specificity for high-grade ADC subtype-detecting. KEY POINTS: • The radiomic values extracted from lung adenocarcinoma with "near-pure" histological subtypes provide useful information for high-grade (micropapillary and solid) components detection. • Using near-pure radiomic features and patch-wise image analysis, high-grade components of lung adenocarcinoma can be predicted with high sensitivity and moderate specificity. • Using near-pure radiomic features and patch-wise image analysis has potential role in facilitating the prediction of the presence of high-grade components in lung adenocarcinoma prior to surgical resection.

15.
Br J Neurosurg ; : 1-11, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410353

RESUMO

PURPOSE: Rhabdomyolysis is a clinical syndrome with the potential to cause cardiac arrhythmias, renal failure, and even death. Currently, there are no studies regarding risk factors for developing post-operative rhabdomyolysis (POR) after spinal fusion surgeries. Our objective was to study risk factors associated with, and to develop a decision-making framework for post-operative rhabdomyolysis after spinal fusion surgery. METHODS: We performed a retrospective cohort study of all spinal fusions of three or more levels over 2.25 years by a single surgeon at two centers. POR was defined as a creatine phosphokinase (CPK) greater than 2000 IU/L. RESULTS: 76 surgical procedures on 72 patients were identified. Rate of POR in our cohort was 22% (17/76). Male sex was associated with POR (p < 0.05). Previously validated risk factors: younger age, lower ASA score, elevated BMI, higher pre-operative creatinine, increased intraoperative blood loss, specific surgical positions, and length of surgery, were not associated with POR. In a logistic regression model, male gender increases the odds of POR in all patients 5.82-fold (p = 0.047). In patients without a second surgery within seven days, a logistic regression model suggests each additional level fused via transpsoas approach, and male gender, increases the risk of POR 1.81-times (p = 0.015), and 6.26-times (p = 0.047), respectively. In patients with posterior fusions, a logistic regression model suggests increasing the number of lateral levels fused via transpsoas approach in the same surgery, and male gender, increases the risk of POR 1.68-times and 6.34-times, respectively. In these same subgroups, increased thickness of the psoas major in lateral transpsoas fusions increased risk of POR (p = 0.023, p = 0.046, respectively). CONCLUSIONS: In spinal fusions, increasing the number of lateral levels fused via transpsoas approach, and male gender, predispose patients to increased risk of POR in those without a second surgery within seven days, and in those with a simultaneous posterior fusion.

16.
Nat Commun ; 12(1): 186, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420036

RESUMO

Stable solid electrolyte interface (SEI) is highly sought after for lithium metal batteries (LMB) owing to its efficient electrolyte consumption suppression and Li dendrite growth inhibition. However, current design strategies can hardly endow a multifunctional SEI formation due to the non-uniform, low flexible film formation and limited capability to alter Li nucleation/growth orientation, which results in unconstrained dendrite growth and short cycling stability. Herein, we present a novel strategy to employ electrolyte additives containing catechol and acrylic groups to construct a stable multifunctional SEI by in-situ anionic polymerization. This self-smoothing and robust SEI offers multiple sites for Li adsorption and steric repulsion to constrain nucleation/growth process, leading to homogenized Li nanosphere formation. This isotropic nanosphere offers non-preferred Li growth orientation, rendering uniform Li deposition to achieve a dendrite-free anode. Attributed to these superiorities, a remarkable cycling performance can be obtained, i.e., high current density up to 10 mA cm-2, ultra-long cycle life over 8500 hrs operation, high cumulative capacity over 4.25 Ah cm-2 and stable cycling under 60 °C. A prolonged lifespan can also be achieved in Li-S and Li-LiFePO4 cells under lean electrolyte content, low N/P ratio or high temperature conditions. This facile strategy also promotes the practical application of LMB and enlightens the SEI design in related fields.

17.
Cell Biol Int ; 45(3): 674-685, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33314408

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor, which occurs in the head and neck. Current treatments for LSCC are all largely weakened by increasing drug resistance. Our study aimed to investigate the effects of long noncoding RNA (lncRNA) H19 on drug resistance in LSCC. In our study, we found that the level of H19 was sharply upregulated in LSCC tissues and drug-resistant cells compared with the control. Besides, the expression of high-mobility group B1 (HMGB1) was elevated, and microRNA107 (miR-107) was suppressed in drug-resistant cells compared with the control. Further study revealed that the interference of H19 by short hairpin RNA (shRNA) effectively suppressed high autophagy level and obvious drug resistance in drug-resistant cells. Besides that, miR-107 was predicted as a target of H19 and inhibiting effects of H19 shRNA on autophagy and drug resistance were both reversed by miR-107 inhibitor. Moreover, HMGB1 was predicted as a target of miR-107 in LSCC cells and knockdown of HMGB1 was able to suppress autophagy and drug resistance in LSCC cells. In addition, our investigation demonstrated that H19 shRNA exerted an inhibiting effect on autophagy and drug resistance by downregulating HMGB1 by targeting miR-107. Finally, the in vivo experiment revealed that LV-H19 shRNA strongly suppressed drug resistance compared with the usage of cisplatin individually. Taken together, our research indicated an H19-miR-107-HMGB1 axis in regulating the autophagy-induced drug resistance in LSCC in vitro and in vivo, providing novel targets for molecular-targeted therapy and broadening the research for LSCC.

18.
Cancer Lett ; 501: 147-161, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33383154

RESUMO

At present, anti-angiogenic drugs (AADs) are widely used in the systemic treatment of hepatocellular carcinoma (HCC) or other types of cancer, and have achieved good anti-cancer effect, whereas treatment-related proteinuria can affect the routine use of AADs, which in turn abates the overall efficacy. Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy of ACEIs in reducing AAD-related proteinuria and its effect on the anticancer effect of AADs is unknown. Our clinical data showed that some HCC patients experienced tumor progression by ACEIs administration for the treatment of proteinuria caused by AADs. Here, we confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to the change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. In conclusion, for the treatment of proteinuria caused by AADs, ACEIs have no efficacy while also promoting AADs resistance. This finding is of great significance to guide clinical standardized management of side effects of anti-angiogenic therapy for cancer patients.

19.
Clin Imaging ; 71: 170-177, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33285405

RESUMO

AIM: To assess the safety and efficacy of CT-guided microwave ablation (MWA) of hepatocellular carcinoma (HCC) near large blood vessels and the diaphragm by analyzing procedural complications and local tumor progression (LTP). METHODS: From October 2013 through January 2019, 80 patients (54 males and 26 females) with 136 tumors who underwent CT-guided MWA of HCC were included in this retrospective analysis. MWA was performed on 43 perivascular HCC (≤5 mm from a vessel measuring ≥5 mm in diameter), 38 subdiaphragmatic HCC (≤5 mm from diaphragm), and 64 control HCC. Risk factors for local tumor progression (LTP), overall survival, and complications were analyzed using the Chi-square and Cox proportional hazards model methods. RESULTS: The technical success rate of MWA was 100%. Complication incidence was not significantly different between perivascular and control tumors (20.9% vs 10.9%; p = 0.155) or between subdiaphragmatic and control tumors (21.1% vs 10.9%; p = 0.163). The effect of lesion location on LTP disappeared while controlling for age and lesion size. There was no significant difference in median survival time between patients who had only control tumors (38.8 months) compared to patients with at least one perivascular or subdiaphragmatic tumor (42.5 months; p = 0.098). CONCLUSION: CT-guided percutaneous MWA of perivascular and subdiaphragmatic HCC tumors is safe and effective. The local tumor recurrence and survival was not significantly different compared to control tumors.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33295049

RESUMO

BACKGROUND: Whether maternal vitamin D affects offspring socioemotional development in early childhood has been underexplored. OBJECTIVES: This study examined associations between maternal vitamin D during in the 3rd trimester and offspring socioemotional development between 30 and 59 months. METHODS: Data from 87 maternal-offspring pairs enrolled in the National Children's Study were used. Total plasma maternal vitamin D (25-hydroxyergocalciferol + 25-hydroxycholecalciferol) was measured between 28 and 35 gestational weeks and categorised as quartiles (Q). Multivariable regression models, adjusting for maternal race/ethnicity, education, and prepregnancy body mass index (BMI [kg/m2 ]), were used to estimate the association between vitamin D and offspring scores on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). RESULTS: The mean (standard deviation) vitamin D concentration was 86.5 (27.8) nmol/L. The median (range) BITSEA problem score was 6.0 (0.0-30.0), and competence score was 19.0 (7.0-22.0). Maternal vitamin D was inversely related to offspring problem scores. Compared to offspring of women with 25(OH)D in Q1, offspring problem scores were -4.80 (95% confidence interval [CI] -8.29, -1.33) units lower for Q2 vs Q1, -5.64 (95% CI -9.60, -1.68) units lower for Q3 vs Q1, and -4.70 (95% CI -8.59, -0.82) units lower for Q4 vs Q1. Vitamin D was not associated with offspring competence score. CONCLUSIONS: Higher maternal vitamin D was associated with lower offspring behaviour problems and not associated with socioemotional competence. These data indicate the association of maternal vitamin D and offspring development may be dependent on the specific developmental component being investigated.

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