Nitrogen‐doped carbon (NC) materials have been proposed as next‐generation oxygen reduction reaction (ORR) catalysts to significantly improve scalability and reduce costs, but these alternatives ...usually exhibit low activity and/or gradual deactivation during use. Here, we develop new 2D sandwich‐like zeolitic imidazolate framework (ZIF) derived graphene‐based nitrogen‐doped porous carbon sheets (GNPCSs) obtained by in situ growing ZIF on graphene oxide (GO). Compared to commercial Pt/C catalyst, the GNPCSs show comparable onset potential, higher current density, and especially an excellent tolerance to methanol and superior durability in the ORR. Those properties might be attributed to a synergistic effect between NC and graphene with regard to structure and composition. Furthermore, higher open‐circuit voltage and power density are obtained in direct methanol fuel cells.
Nitrogen‐doped: A new oxygen reduction reaction electrocatalyst was obtained from ZIF‐derived porous carbon and graphene. The catalyst exhibits high activity, superior tolerance to methanol, and good stability in comparison to commercial Pt/C catalyst.
The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the ...spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4
or CD8
T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.
Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological ...complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c‐MYC). Additionally, KPNA2 knockdown regulated CSC‐related gene expression in radioresistant cells. Next‐generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2‐mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1‐STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.
Nuclear KPNA2 promotes radioresistance and regulates cancer stem cell properties in lung adenocarcinoma cells. A loop between PLSCR1 and STAT1 is involved in KPNA2‐mediated radioresistance.
To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units ...than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.
Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and ...how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR‐103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR‐103‐expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR‐103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR‐103‐expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR‐103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR‐103‐expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR‐103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell‐secreted miR‐103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE‐Cadherin (VE‐Cad), p120‐catenin (p120) and zonula occludens 1. Moreover, miR‐103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells. Conclusion: Hepatoma cell‐secreted exosomal miR‐103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR‐103 as a potential therapeutic target and a predictive marker for HCC metastasis. (Hepatology 2018).
Graphene and its derivatives have unique physical and chemical properties that make them promising vehicles for photothermal therapy (PTT)-based cancer treatment. With intrinsic near-infrared (NIR) ...absorption properties, graphene-based nanomaterials can be used for PTT and other therapeutics, particularly in combination therapy, to provide successful thermal ablation of cancer cells. In the recent years, advances in graphene-based PTT have produced efficient and efficacious tumor inhibition via nanomaterial structural design and different functionalizations of graphene-derived nanocomposites. Graphene-based nanosystems exhibit multifunctional properties that are useful for PTT applications including enhancement of multimodalities, guided imaging, enhanced chemotherapy and low-power efficient PTT for optimum therapeutic efficiency. Therefore, in this review, we address critical issues and future aspects of PTT-based combination therapy.
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Gefitinib, erlotinib and afatinib are approved for first‐line treatment of advanced non‐small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, ...the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first‐line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians’ choice. The median overall survival (OS) was 37.0 months. Although the baseline characteristics of patients were unequal, progression‐free survival and OS did not differ among the 3 groups. Multivariate analysis found that gefitinib (adjusted odds ratio aOR 3.29, 95% confidence interval CI, 1.15–9.46, p = 0.027), EGFR TKI treatment duration more than 13 months (aOR 3.16, 95% CI, 1.20–8.33, p = 0.020), male (aOR 3.25, 95% CI, 1.10–9.66, p = 0.034), initial liver metastasis (aOR 4.97, 95% CI 1.18–20.96, p = 0.029) and uncommon EGFR mutation (aOR 0.14, 95% CI, 0.02–0.97, compared to EGFR deletion 19, p = 0.047) were independent factors for secondary T790M mutation. In real‐world practice, choosing first line EGFR TKI based on the patients’ clinical characteristics yielded good clinical outcomes. First‐line gefitinib, longer EGFR TKI treatment duration, male, initial liver metastasis and uncommon EGFR mutations may be independent factors for secondary EGFR T790M mutation.
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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly are used as first‐line therapy for advanced non‐small cell lung cancer (NSCLC). However, the actual extent of their clinical performance, including impacts on secondary EGFR T790M mutation, the most frequent EGFR‐TKI resistance mechanism, remains uncertain. Here, analyses of first‐line EGFR‐TKIs afatinib, erlotinib, gefitinib in advanced EGFR‐mutant NSCLC, with TKIs chosen by clinicians’ discretion, shows median overall survival to be 37 months, which is longer than previously reported. Secondary EGFR T790M mutation was independently associated with multiple factors, including first‐line gefitinib therapy and EGFR TKI use for more than 13 months.
Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower ...levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP‐13) expression are higher in prostate cancer patients than in healthy cancer‐free individuals. Mechanistic investigations revealed that melatonin inhibits MMP‐13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c‐Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP‐13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.
Melatonin acts on the MT1 receptor and inhibits phospholipase C (PLC) and p38 signal cascades, subsequently suppresses matrix metallopeptidase 13 (MMP‐13) expression through the c‐Jun‐dependent pathway, leading to the reduction of prostate cancer metastasis. This is the first indication that melatonin impedes metastasis via the targeting of MMP‐13 in prostate cancer cells, based on evidence from basic and clinical studies.
Computing-in-memory (CIM) based on embedded nonvolatile memory is a promising candidate for energy-efficient multiply-and-accumulate (MAC) operations in artificial intelligence (AI) edge devices. ...However, circuit design for NVM-based CIM (nvCIM) imposes a number of challenges, including an arealatency-energy tradeoff for multibit MAC operations, patterndependent degradation in signal margin, and small read margin. To overcome these challenges, this article proposes the following: 1) a serial-input non-weighted product (SINWP) structure; 2) a down-scaling weighted current translator (DSWCT) and positive-negative current-subtractor (PN-ISUB); 3) a currentaware bitline clamper (CABLC) scheme; and 4) a triple-margin small-offset current-mode sense amplifier (TMCSA). A 55-nm 1-Mb ReRAM-CIM macro was fabricated to demonstrate the MAC operation of 2-b-input, 3-b-weight with 4-b-out. This nvCIM macro achieved T MAC = 14.6 ns at 4-b-out with peak energy efficiency of 53.17 TOPS/W.
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