Inorganic films possess much higher thermoelectric performance than their organic counterparts, but their poor flexibilities limit their practical applications. Here, Sb2Te3/Tex hybrid thin films ...with high thermoelectric performance and flexibility, fabricated via a novel directional thermal diffusion reaction growth method are reported. The directional thermal diffusion enables rationally tuning the Te content in Sb2Te3, which optimizes the carrier density and leads to a significantly enhanced power factor of >20 µW cm–1 K–2, confirmed by both first‐principles calculations and experiments; while dense boundaries between Te and Sb2Te3 nanophases, contribute to the low thermal conductivity of ≈0.86 W m–1 K–1, both induce a high ZT of ≈1 in (Sb2Te3)(Te)1.5 at 453 K, ranking as the top value among the reported flexible films. Besides, thin films also exhibit extraordinary flexibility. A rationally designed flexible device composed of (Sb2Te3)(Te)1.5 thin films as p‐type legs and Bi2Te3 thin films as n‐type legs shows a high power density of >280 µW cm–2 at a temperature difference of 20 K, indicating a great potential for sustainably charging low‐power electronics.
A high ZT of ≈1 at 453 K is achieved in an inorganic Sb2Te3/Te hybrid thin film via a novel directional thermal diffusion reaction growth method with extraordinary flexibility, and the rationally designed flexible device shows a high power density by a low‐temperature difference.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk ...factors of COVID-19 disease severity for patients with cancer and COVID-19.
In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807.
Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22–38) in patients with cancer and 27 days (20–35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 64% of 232 vs 166 32% of 519; odds ratio OR 3·61 95% CI 2·59–5·04; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05–6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01–1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03–2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71–0·98; p=0·031), and reduced albumin–globulin ratio (0·12, 0·02–0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer.
Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19.
China National Natural Science Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. Exosomal miRNAs from cancer cells play crucial roles in mediating cell-cell communication and ...tumor-microenvironment cross talk, specifically in enabling metastasis and promoting angiogenesis. We focused on miR-9 that was identified as a tumor suppressor previously in nasopharyngeal carcinoma (NPC) tumorigenesis.
Differential centrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to isolate and identify exosomes. Quantitative PCR and western blotting analysis were used to detect miR-9, pri-miR-9, CD63, TSG101, MDK, P70S6K P-Ser424 and PDK1 P-Ser241 expression. Laser confocal microscopy was used to trace exosomal miR-9 secreted by NPC cells into HUVECs. The effect of exosomal miR-9 on cell migration and tube formation of HUVECs in vivo and vitro was assessed by using migration assay, tube formation assay and matrigel plug assay, respectively. Bioinformatics analysis and luciferase reporter assay were utilized to confirm the binding of exosomal miR-9 to the 3'untranslated region (3'-UTR) of MDK, while Phosphorylation Array was performed to identify AKT Pathway in HUVECs treated with exosomal miR-9. Furthermore, Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to detected miR-9, CD31 and MDK expression in human NPC tumor samples.
NPC cells transfected with miR-9-overexpressing lentivirus, released miR-9 in exosomes. Exosomal miR-9 directly suppressed its target gene - MDK in endothelial cells. Mechanistic analyses revealed that exosomal miR-9 from NPC cells inhibited endothelial tube formation and migration by targeting MDK and regulating PDK/AKT signaling pathway. Additionally, the level of MDK was upregulated in NPC tumor samples and was positively correlated with microvessel density. Notably, the level of exosomal miR-9 was positively correlated with overall survival, and MDK overexpression was positively associated with poor prognosis in NPC patients, suggesting the clinical relevance and prognostic value of exosomal miR-9 and MDK.
Taken together, our data identify an extracellular anti-angiogenic role for tumor-derived, exosome-associated miR-9 in NPC tumorigenesis and prompt further investigation into exosome-based therapies for cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Many in vitro studies have shown that tea catechins had vevarious health beneficial effects. However, inconsistent results between in vitro and in vivo studies or between laboratory tests and ...epidemical studies are observed. Low bioavailability of tea catechins was an important factor leading to these inconsistencies. Research advances in bioavailability studies involving absorption and metabolic biotransformation of tea catechins were reviewed in the present paper. Related techniques for improving their bioavailability such as nanostructure-based drug delivery system, molecular modification, and co-administration of catechins with other bioactives were also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chemoresistance remains a major obstacle to successful treatment of breast cancer. Although soluble tumor necrosis factor-α (sTNF-α) has been implicated in mediating drug-resistance in human cancers, ...whether transmembrane tumor necrosis factor-α (tmTNF-α) plays a role in chemoresistance remains unclear. Here we found that over 50% of studied patients expressed tmTNF-α at high levels in breast cancer tissues and tmTNF-α expression positively correlated with resistance to anthracycline chemotherapy. Alteration of tmTNF-α expression changed the sensitivity of primary human breast cancer cells and breast cancer cell lines to doxorubicin (DOX). Overexpression of N-terminal fragment (NTF) of tmTNF-α, a mutant form with intact intracellular domain of tmTNF-α to transmit reverse signals, induced DOX-resistance. Mechanistically, the tmTNF-α/NTF-ERK-GST-π axis and tmTNF-α/NTF-NF-κB-mediated anti-apoptotic functions were required for tmTNF-α-induced DOX-resistance. In a xenograft mouse model, the combination of tmTNF-α suppression with chemotherapy significantly enhanced the efficacy of DOX. Our data indicate that tmTNF-α mediates DOX-resistance through reverse signaling and targeting tmTNF-α may be beneficial for the treatment of DOX-resistant breast cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related ...to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
One of the most striking characteristics of nasopharyngeal carcinoma (NPC) is the presence of a very abundant immune cells infiltrate containing mainly T‐lymphocytes. The purpose of this ...study was to present our analysis providing a comprehensive characterization of antitumor inflammatory response in NPC.
Methods
The densities of 9 types of inflammatory cells were assessed in 197 patients with NPC, including CD3 + T‐lymphocytes, CD8 + cytotoxic T‐lymphocytes, CD20 + B‐lymphocytes, CD56 + natural killer (NK) cells, FOXP3 + regulatory T‐lymphocytes, CD1a + immature dendritic cells, CD83 + mature dendritic cells, neutrophil elastase + neutrophils, and tryptase + mast cells. We characterized the inflammatory infiltrate in relation to clinical stage and patient survival. The expression of programmed death‐1 (PD‐1) on tumor‐infiltrating lymphocytes (TILs) was also detected. The correlations between PD‐1 expression and clinical characteristics and posttreatment outcome were analyzed.
Results
The patients with NPC with a low density of tumor‐infiltrating FOXP3+, CD8 + T‐lymphocytes, neutrophils, and mast cells showed a significantly longer overall survival (OS) and progression‐free survival (PFS). However, patients with a high density of NK cells showed a better OS and PFS. The densities of NK cells and mast cells could be served as biomarkers for predicting recurrence or distant metastasis in patients with NPC. Moreover, PD‐1 positivity predicted poor prognosis in patients with NPC.
Conclusion
The densities of inflammatory cells are correlated with the prognosis of patients with NPC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Non‐small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)‐based drugs are still ...one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt‐based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi‐omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.
A novel albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)), based on the Pt(IV) drug and nanodelivery system, exhibits superior delivery effect in both in vitro and in vivo models of non‐small cell lung cancer (NSCLC). HSA@Pt(IV) achieves antitumor effects by consuming glutathione and disrupting intracellular metal ion homeostasis, especially promoting Fe element accumulation to induce ferroptosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Empirical studies have demonstrated the importance of emotion regulation for teachers' professional development. We adopted a person‐centered approach to explore primary school teachers' emotion ...regulation and its impact on occupational well‐being, job burnout, and resilience. To understand the potential types of emotion regulation, we conducted a survey in different primary schools. Both antecedent‐ and response‐focused emotion regulation are important strategies; previous studies revealed that the former is superior to the latter. However, there is a lack of person‐centered research on the pros and cons of such emotion regulation. 366 primary school teachers (333 female teachers; Mage = 37.30, SDage = 9.46) participated in this survey. The emotion regulation patterns were clarified based on latent profile analysis (LPA). The results revealed associations among these patterns and job burnout, occupational well‐being and resilience. LPA revealed the following: (1) three typical emotion regulation types: the low antecedent‐ and low response‐focused emotion regulation group (12%), the high antecedent‐ and low response‐focused emotion regulation group (63%), and the low antecedent‐ and high response‐focused emotion regulation group (25%). (2) The teachers in the high antecedent‐ and low response‐focused emotion regulation group had the lowest level of job burnout and the highest level of occupational well‐being. Those in the low antecedent‐ and low response‐focused emotion regulation group had the strongest psychological resilience.
HIGHLIGHTS
There are three typical emotion regulation types: low antecedent‐ and low response‐focused emotion regulation, high antecedent‐ and low response‐focused emotion regulation, and low antecedent‐ and high response‐focused emotion regulation.
Teachers in the group with high antecedent‐ and low response‐focused emotion regulation had the lowest level of job burnout and the highest level of occupational well‐being.
Those in the low antecedent‐ and low response‐focused emotion regulation group had the strongest psychological resilience.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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