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1.
Artigo em Inglês | MEDLINE | ID: mdl-35014150

RESUMO

Single-nanoparticle electrochemistry offers electrochemical behaviors of individual entity beyond the ensemble system. An electric double layer (EDL) exists on any charged particle-liquid interface because of counter-ions accumulation, while direct measuring the interfacial ion migration remains a challenge.  Herein, a plasmonic-based transient microscopic method, with a temporal resolution of 1-2 µs, was demonstrated to directly track the ion migration dynamics on single charged nanoparticles. We found that the dynamics of EDL formation might deviate significantly from the prediction of classical resistance-capacitance (RC) model under nanoscale and transient conditions. Under ultrafast charging, due to the limit migration rate of ions in the solution, the actual time scale of the EDL formation could be up to 5 times slower than the predicted value from the RC model. We then proposed a new theoretical model to describe the transient dynamics of EDL formation. These results may expand our current knowledge about nano-electrochemistry and transient electrochemistry.

2.
J Hematol Oncol ; 15(1): 1, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991679

RESUMO

BACKGROUND: The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. METHODS: To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. RESULTS: A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. CONCLUSIONS: This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 ( https://clinicaltrials.gov/ct2/show/NCT01207440 ).

3.
Adv Sci (Weinh) ; : e2103845, 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35001541

RESUMO

The propensity of sodium anode to form uniform electrodeposit is bound up with the nature of electrode surface and regulation of Na-ion flux, as well as distribution of electronic field, which is quite crucial for high-areal-capacity sodium metal batteries (SMBs). Herein, a novel metallic sodium/sodium-tin alloy foil anode (Na/NaSn) with 3D interpenetrated network and porous structure is prepared through facile alloy reaction. The strong sodiophilic properties of sodium-tin alloy can lower the nucleation energy, resulting in smaller depositing potential and strong adsorption of Na+ , while synergistic effect of porous skeleton and additional potential difference (≈0.1 V) between Na and Na-Sn alloy (Na15 Sn4 ) can alleviate volume expansion, redistribute the Na-ion flux and regulate electronic field, which favors and improves homogeneous Na deposition. The as-fabricated Na/NaSn electrode can endow excellent plating/stripping reversibility at high areal capacity (over 1600 h for 4 mAh cm-2 at 1 mA cm-2 and 2 mAh cm-2 at 2 mA cm-2 ), fast electrochemical kinetics (500 h under 4 mAh cm-2 at 4 mA cm-2 ) and superior rate performances. A novel strategy in the design of high-performance Na anodes for large-scale energy storage is provided.

4.
Materials (Basel) ; 15(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35009530

RESUMO

China's highway asphalt pavement has entered the stage of major repair, and improving the utilization rate of recycled asphalt pavement (RAP) is the main issue. The key link affecting the performance of recycled asphalt mixtures is the regeneration of aged asphalt, and the effect of the regenerant dosing on the high-temperature performance and viscosity of aged asphalt is the main content to be studied in this research. The aging behavior of asphalt seriously affects the roadworthiness of asphalt mixtures. In this study, we investigated the effect of changes in the microscopic properties of the aged asphalt on its viscosity properties during regeneration using gel permeation chromatography (GPC), Fourier-transform infrared spectroscopy (FTIR), and atomic force microscopy (AFM) as well as Brinell viscosity tests. This study simulated asphalt aging by the RTFOT test, and then we obtained an aged asphalt with a needle penetration of 30. We prepared different regenerated asphalts by adding regeneration agent with doses of 2%, 4%, and 6% to the aged asphalt. The results showed that the regeneration agent could effectively reduce the viscosity of the aged asphalt, which can play a positive role in improving the construction and ease of the aged asphalt. Rejuvenation agents affected the aging asphalt sulfoxide and carbon group indices. Moreover, rejuvenation agents can also significantly reduce the intensities of their characteristic functional group indices. The results of the AFM test showed that the increase in the dose of regeneration agent increased the number of the asphalt bee-like structures and decreased the area of individual bee-like structures. The results of the GPC test were consistent with the results of the AFM test, and the increase in the dose of regeneration agent reduced the asphalt macromolecule content. The viscosity properties and microstructure of the aged asphalt changed positively after the addition of the regeneration agent, indicating that the regeneration agent had a degrading and diluting effect on macromolecules.

5.
J Clin Pathol ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039449

RESUMO

AIMS: GATA-binding protein 3 (GATA3) is a zinc finger transcription factor with diverse biological functions and is an excellent diagnostic marker for breast and urothelial carcinoma. We aimed to study GATA3 expression in oesophageal squamous cell carcinoma (SCC) and its significance with respect to histological features, clinical parameters and overall survival. METHODS: We characterised GATA3 immunohistochemistry in 40 patients with oesophageal SCC. Electronic medical records were reviewed for clinical and follow-up information, as well as patient survival. RESULTS: Eleven (28%) oesophageal SCC were positive for GATA3. The predominant stain patterns were patchy, with either mild or moderate intensities. Patients with GATA3-positive tumours showed significantly shorter overall survival than those with GATA3-negative tumours (p=0.023, Kaplan-Meier survival analysis with log-rank test). In the multivariate Cox proportional hazards regression model, GATA3 positivity was an independent adverse prognostic factor for overall survival (p=0.019, HR 5.671). Surgery, definitive chemotherapy and/or radiotherapy, and initial clinical stage were confirmed as independent prognostic factors. CONCLUSION: To the best of our knowledge, this is the first study to investigate the incidence of GATA3 positivity in oesophageal SCC and showed GATA3 positivity is associated with poor prognosis in oesophageal SCC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34973094

RESUMO

PURPOSE: To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). METHODS: Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iß (IL-1ß) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1ß. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. RESULTS: Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1ß and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1ß compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). CONCLUSION: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

7.
Carbohydr Polym ; 278: 118950, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973766

RESUMO

Cancer is a complex disease, and blocking tumor angiogenesis has become one of the most promising approaches in cancer therapy. Here, an exopoly heteropolysaccharide (AQP70-2B) was firstly isolated from Akebia quinata. Monosaccharide composition indicated that the AQP70-2B was composed of rhamnose, glucose, galactose, and arabinose. The backbone of AQP70-2B consisted of →1)-l-Araf, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, →4)-d-Glcp-(1→, →6)-d-Galp-(1→, and →1)-d-Rhap residues. Based on the close relationship between selenium and anti-tumor activity, AQP70-2B was modified with selenium to obtain selenized polysaccharide Se-AQP70-2B. Then, a series of methods for analysis and characterization, especially scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS), indicated that Se-AQP70-2B was successfully synthesized. Furthermore, zebrafish xenografts and anti-angiogenesis experiments indicated that selenization could improve the antitumor activity by inhibiting tumor cell proliferation and migration and blocking angiogenesis.

8.
Sci Total Environ ; 817: 152939, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35016925

RESUMO

Pressurized electro-dewatering technology is considered to be one of the most effective methods for improving dewatering performance of sewage sludge. In this paper, four dewatering protocols were developed to further explore the coupling mechanism of sludge dewatering through mechanical pressure, electric field and their joint. The results showed that the dewatering performance of the four dewatering protocols were as follows: pressurized electro-dewatering with constant voltage gradient mode (G-PEDW) > first mechanical dewatering then electro-dewatering > mechanical dewatering > electro-dewatering. The coupling mechanism was revealed from the perspectives of pore structure and moisture distribution of sludge cakes. The pore structure was discussed in detail from the whole pore size distribution and fractal dimension. The fractal dimension could quantitatively describe the change of pore structure. The moisture distribution was analyzed by the thermogravimetric differential scanning calorimetry test. The results showed that the electric field could reduce bound strength of moisture and produce new micro-pores to build more water flow paths, the water was discharged through interior capillary channels, and mechanical pressure could accelerate the water removing process. Response surface method was used to establish an empirical prediction model of G-PEDW, and discussed the selection of optimal parameters. The R-square values of mathematical models of moisture content and energy consumption were as high as 0.9863 and 0.9838, respectively, which was more advanced than other mathematical models. Experiments showed that G-PEDW could reduce the time to 20 min or reduce the energy consumption to 7.1 Wh/kg•H2O when the target moisture content was set to 41.7%.

9.
Cancer Invest ; : 1-6, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35020560

RESUMO

This study was carried out to demonstrate the prognostic value of CD274 (PD-L1 promoter gene) methylation in bladder cancer patients. UCSC Xena database was searched for relevant information on PD-L1 (CD274) methylation and PD-L1 mRNA expression in bladder cancer. 407 bladder patients were included in our analyses. Multivariate analysis revealed that PD-L1 methylation was an independent predictor for OS (P = 0.037). Moreover, PD-L1 methylation might be a prognostic biomarker for immunotherapy response. However, PD-L1 methylation and PD-L1 mRNA expression was not statistically associated with chemotherapy response. In conclusion, PD-L1 methylation was an independent prognostic factor for bladder cancer patients.

11.
Haematologica ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35045690

RESUMO

The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. We performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity, the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients, a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.

13.
Dis Markers ; 2022: 7878602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35059045

RESUMO

Objective: To clarify the protective effect of simvastatin on myocardial ischemia reperfusion injury (MIRI) and the underlying mechanism. Materials and Methods: The MIRI model in rats was firstly constructed. Twenty-four male rats were randomly assigned into the sham group, ischemia-reperfusion (I/R) group, and simvastatin group, with 8 rats in each group. Contents of superoxide dismutase (SOD) and malondialdehyde (MDA), as well as serum levels of CK and inflammatory factors, in rats were determined by the enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH) activity in the three groups was examined. Through flow cytometry and Cell Counting Kit-8 (CCK-8) assay, apoptosis and viability in each group were detected, respectively. Relative levels of HMGB1, Kruppel-like factor 2 (KLF2), eNOS, and thrombomodulin (TM) were finally determined. Results: Simvastatin treatment markedly enhanced SOD activity and reduced contents of MDA, LDH, and creatine kinase (CK) in MIRI rats. The increased apoptosis and decreased viability following MIRI were partially reversed by simvastatin treatment. Besides, MIRI resulted in the upregulation of inflammatory factors and chemokines. Their elevations were abolished by simvastatin. In MIRI rats, simvastatin upregulated KLF2 and p-eNOS. Conclusions: Simvastatin protects inflammatory response at post-MIRI through upregulating KLF2, thus improving cardiac function.

14.
Int Immunopharmacol ; 105: 108533, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35063754

RESUMO

Iron oxide nanoparticles (IONPs) are widely used in cosmetics, food additives, and biomedical fields. There are a few adverse effects of IONPs according to clinical reports and animal studies. However, the immunotoxicity and, in particular, the size effects and mechanisms of IONPs on macrophages have not been fully clarified. This study aimed to explore the impacts of 10 nm and 30 nm IONPs on immune responses both in mice and bone marrow-derived macrophages (BMMs). We found that 10 mg/kg IONPs elevated the number of neutrophils and the level of interleukin-6 (IL-6) in peritoneal lavage fluids in mice. IONPs also provoked BMMs and induced the production of IL-6 and tumor necrosis factor-α (TNF-α). The impacts of IONPs on inflammatory responses were size-dependent, and 30 nm IONPs were stronger. Consistently, RNA-sequencing and bioinformatic analysis showed that 30 nm IONPs activated numerous biological processes, including many immune responses, endoplasmic reticulum (ER) stress, and oxidative stress. Furthermore, the inflammatory response caused by IONPs could be attenuated by blocking actin polymerization, ER stress, or oxidative stress. This study is helpful to understand the biosafety of IONPs and protect humans from their potential adverse immune effects.

15.
J Med Chem ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35041407

RESUMO

Studies have shown that circRNAs are important regulatory molecules involved in cell physiology and pathology. Herein, we analyzed the role of circ_ZNF512 in cardiomyocyte autophagy of myocardial ischemia/reperfusion (I/R) injury. A mouse model was induced by ligation of the left anterior descending artery followed by reperfusion. An in vitro model was also developed in cultured cardiomyocytes following hypoxia/reoxygenation (H/R) injury. It was established that EGR1 expression was increased in myocardial tissues of I/R mice and H/R-induced cardiomyocytes. Silencing of circ_ZNF512 attenuated its binding to miR-181d-5p, which in turn impaired the EGR1 expression by targeting its 3'-UTR, thus promoting the autophagy of cardiomyocytes and suppressing cell apoptosis to alleviate myocardial tissue injury. Additionally, the circ_ZNF512/miR-181d-5p/EGR1 crosstalk activated the mTORC1/TFEB signaling pathway, increasing mTORC1 expression while suppressing TFEB expression. Together, circ_ZNF512 knockdown protects against myocardial I/R injury, which may be a potential therapeutic approach for preventing myocardial I/R injury.

16.
J Clin Ultrasound ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044709

RESUMO

The occlusion of the innominate artery caused a significant decrease in the distal end of the right subclavian artery and the right common carotid artery, internal carotid artery, and external carotid artery (ECA). Due to the different pressure and the abundant communicating arteries between the ECA and the bilateral vertebral artery (VA), different paths of blood steal in the anterior and posterior circulation occurred.

17.
Brain Res ; 1779: 147785, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35032442

RESUMO

The goal of this study was to explore the mechanism of action of DL-3-n-butylphthalidein (NBP) the treatment of vascular dementia (VD) in mice. A vascular dementia mouse model was established with repeated cerebral ischemia/reperfusion (I/R), followed by administration of two different doses of NBP for 28 days. A Morris water maze was used to detect any changes in spatial cognition, while H&E staining was used to observe any histopathological changes in the hippocampus. The number of Caspase-3 and Caspase-9 positive neurons in the hippocampal CA1 region were also assessed using immunohistochemistry. The expression of Nrf2, Sirt3, and autophagy-related factors LC3 II/I and p62 in the hippocampus were detected by Western blotting. The results indicated that NBP treatment ameliorated learning and memory deficits, attenuated pathological damage in the CA1 regions, and reduced autophagy and apoptosis via the Nrf2/SIRT3 pathway after repeated cerebral I/R. Therefore, NBP treatment can improve the learning and cognitive memory of VD mice, possibly through the inhibition of autophagy and apoptosis mediated by the Nrf2/SIRT3 signaling pathway.

18.
Micromachines (Basel) ; 13(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35056254

RESUMO

A chip-scale tunable optical filter is indispensable to meeting the demand for reconfigurability in wavelength division multiplexing systems, channel routing, and switching, etc. Here, we propose a new scheme of bandwidth tunable band-pass filters based on a parity-time (PT) symmetric coupled microresonator system. Large bandwidth tunability is realized on the basis of the tuning of the relative resonant frequency between coupled rings and by making use of the concept of the exception point (EP) in the PT symmetric systems. Theoretical investigations show that the bandwidth tuning range depends on the intrinsic loss of the microresonators, as well as on the loss contrast between the two cavities. Our proof-of-concept device confirms the tunability and shows a bandwidth tuning range from 21 GHz to 49 GHz, with an extinction ratio larger than 15 dB. The discrepancy between theory and experiment is due to the non-optimized design of the coupling coefficients, as well as to fabrication errors. Our design based on PT symmetry shows a distinct route towards the realization of tunable band-pass filters, providing new ways to explore non-Hermitian light manipulation in conventional integrated devices.

19.
Micromachines (Basel) ; 13(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35056255

RESUMO

Information capacity of single-mode fiber communication systems face fundamental limitations imposed by optical nonlinearities. Spatial division multiplexing (SDM) offers a new dimension for upgrading fiber communication systems. Many enabling integrated devices, such as mode multiplexers and multimode bending with low crosstalk, have been developed. On the other hand, all-optical signal processing (AOSP) can avoid optical to electrical to optical (O-E-O) conversion, which may potentially allow for a low cost and green operation for large-scale signal processing applications. In this paper, we show that the system performance of AOSP can be pushed further by benefiting from the existing technologies developed in spatial mode multiplexing (SDM). By identifying key technologies to balance the impacts from mode-dependent loss, crosstalk and nonlinearities, three-channel 40 Gbit/s optical logic operations are demonstrated using the first three spatial modes in a single multimode waveguide. The fabricated device has a broadband four-wave mixing operation bandwidth (>20 nm) as well as high conversion efficiency (>-20 dB) for all spatial modes, showing the potential for a large-scale signal processing capacity with the combination of wavelength division multiplexing (WDM) and SDM in the future.

20.
J Cell Mol Med ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35023309

RESUMO

The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin-induced diabetic rats, glyoxal-treated R28 cells and hypoxia-treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba-1, TSPO, NF-κB, Nrf2 and inflammation-related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal-treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia-treated microglia, which was largely dampened by FKN. The NF-κB and Nrf2 expressions and intracellular ROS were up-regulated in hypoxia-treated microglia compared with that in normoxia control, and FKN significantly inhibited NF-κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF-κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation-related cytokines and ROS, and protect the retina from diabetes insult.

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