This paper proposes a novel single-stage ac-to-dc light-emitting-diode (LED) driver circuit. A buck-boost power factor (PF) corrector is integrated with a flyback converter. A recycling path is built ...to recover the inductive leakage energy. In this way, the presented circuit can provide not only high PF and low total harmonic distortion but also high conversion efficiency and low switching voltage spikes. Above 0.95 PF and 90% efficiency are obtained from an 8-W LED lamp driver prototype.
Two rare-earth radical complexes Ln(hfac)3NIT-2Py·0.5C7H16 Ln = Tb (1), Dy (2) have been synthesized and characterized structurally as well as magnetically. Both complexes are isomorphous, in which ...the NIT-2Py radical is coordinated to the LnIII ion in a chelating manner. Magnetic studies reveal that complex 1 shows a frequency-dependent, alternating-current magnetic susceptibility typical of a single-molecule magnet, whereas slow magnetic relaxation is observed in 2 under an applied direct-current field.
AbstractTo reduce the ineffective evaporation of plain reservoirs in inland arid areas and improve the effective utilization of reservoirs, this work uses floating plates and floating balls as the ...main covering materials to reduce water surface evaporation. This paper investigates the motion characteristics of two covering materials with different structures under wind and waves through laboratory and field experiments. It analyzes the relation of evaporation inhibition rate of the floating plates and its area and thickness, and adopts the method of adding a counterweight to solve the problem of irregular rotation and easily rolling of the floating balls (the floating ball that serves as the added counterweight is called a tumbler floating ball). Then, it discusses the influence of diameter, counterweight, density, and type of the floating ball on evaporation inhibition rate by using the orthogonal design method and establishes a calculation equation of the water surface evaporation inhibition rate, which is applicable to the experiment area. Results show that: (1) the evaporation inhibition rate of the floating plates is positively correlated with the surface area and thickness, and (2) the influence degree of the four factors on the evaporation rate of the floating balls is diameter > counterweight > density > type of floating balls.
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.
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect ...in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/Pten‐knockout HNSCC mouse model. Notch signaling inhibition using a γ‐secretase inhibitor (GSI‐IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub‐population of myeloid‐derived suppressor cells (MDSCs), tumour‐associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC.
What's new?
Tumor survival depends on sneaking past the body's own immune defenses. Here, the authors probed how cancer cells exploit the Notch signaling pathway to evade immune destruction. Looking at HNSCC cells, they first showed that Notch1 signaling is activated in the tumor cells. Then, they showed that inhibiting the Notch signaling pathway decreased the tumor burden, as well as markedly reducing the production of immunosuppressive cells, such as tumor associated macrophages and immunosuppressive regulatory T cells. Thus, treatments targeting Notch1 could be useful against HNSCC.
New 2p–4f and 2p–3d–4f compounds Tb(hfac)3(NIT-PhNO2)2·0.5C7H16 (1) and Ln(hfac)3(NIT-PhNO2)22Cu(hfac)2(NIT-PhNO2)2 (LnIII = Gd 2, Tb 3; hfac = hexafluoroacetylacetonate; NIT-PhNO2 = ...2-(p-nitrophenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) have been obtained. Complex 1 consists of mononuclear trispin Tb(hfac)3(NIT-PhNO2)2 units in which two radical ligands are ligated to the Tb(III) ion as monodentate ligands through the NO groups, while complexes 2 and 3 contain two kinds of trispin moieties, namely, Ln(hfac)3(NIT-PhNO2)2 and Cu(hfac)2(NIT-PhNO2)2. In the Cu(hfac)2(NIT-PhNO2)2 moiety, the radicals are bonded to the copper(II) ion in the axial positions via the nitroxides. For three compounds, 1D supramolecular chains are formed via the π–π stacking interactions involving the radical ligands. Magnetic investigations show that both Tb complexes exhibit slow relaxation of magnetization at low temperature; strikingly, complex 3 displays a higher energy barrier than that of 1. It represents the first example to use the paramagnetic complex to tune magnetic relaxation of 4f-based compounds.
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms ...regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of
Tgfbr1/Pten
2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4
+
and CD8
+
T cells in HNSCC mice. Notably, the numbers of exhausted PD-1
+
and Tim3
+
T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.
Abstract
Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of ...infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.
We report a unique 3-family cluster of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The transmission of SARS-CoV-2 by individuals with asymptomatic or paucisymptomatic infections likely occurred. SARS-CoV-2 was detected in contaminated environments of 1 household.
Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different ...molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis.
PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis.
Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI 1.061 ~ 1.218, p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI 1.061 ~ 1.182, p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI 0.789 ~ 1.690, p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003 and TNBC molecular subtype HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001 and TNBC molecular subtype HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012.
Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A new type of phosphorus‐doped porous organic polymer (POP) has been readily synthesized through a Heck reaction, which could be used not only as a support but also a ligand for palladium ...nanoparticles. The dual‐functional material supported palladium nanocatalyst was used for the efficient and chemoselective hydrogenation of varieties of nitroarenes and α,β‐unsaturated compounds, as well as for the synthesis of indoles from 2‐nitrophenylacetonitrile under 1 atm hydrogen in green solvents at room temperature. No obvious aggregation and loss of catalytic activity of the new nanocatalyst were observed after 10 runs in the reaction.
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