Aspergillus fumigatus is a common cause of invasive and allergic pulmonary disease. Resting conidia of the filamentous fungus are constantly inhaled, but cause infection only after initiating hyphal growth. In this study, we have explored whether macrophages can distinguish between resting spores and the maturing, potentially invasive form of the fungus. Although macrophages bind and ingest A. fumigatus resting conidia efficiently, there is little inflammatory response; NF-κβ is not activated, inflammatory cytokines are not induced, and reactive oxygen species are not produced. However, maturing A. fumigatus conidia and germ tubes stimulate NF-κβ, secretion of proinflammatory cytokines and production of reactive oxygen by human monocyte-derived macrophages and murine macrophages from multiple anatomical sites. These responses are in part mediated by dectin-1, which binds cell wall β-glucan that is not present on the surface of dormant conidia, but is present after cellular swelling and loss of the hydrophobic proteinaceous cell wall. Dectin-1 binding to germ tubes augments, but is not required for, TLR2-mediated inflammatory cytokine secretion. Dectin-1 recognition of germ tubes also stimulates TNF-α production in the absence of both TLR2 and MyD88 signaling. These data demonstrate one mechanism by which the pulmonary inflammatory response is tailored toward metabolically active cells, thereby avoiding unnecessary tissue damage with frequent inhalation of ubiquitous spores.
Inorganic cesium lead halide perovskites with superb thermal stability show promise to fabricate long-term operational photovoltaic devices. However, the cubic phase (α) of CsPbI 3 with an appropriate band gap is unstable in air. We discover that highly stable α-CsPbI 3 can be obtained in dry air (temperature: 20−30 °C; humidity: 10−20%) by replacing PbI 2 with HPbI 3 in a one-step deposition solution. Furthermore, the band gap of HPbI 3processed α-CsPbI 3 is advantageously reduced from 1.72 to 1.68 eV due to the existence of tensile lattice strain. By employing such an α-CsPbI 3 film in carbon-based perovskite solar cells (C-PSCs), a power conversion efficiency (PCE) of 9.5% is achieved, which is a record value for the α-CsPbI 3 PSCs without hole transport material. Most importantly, over 90% of the initial PCE is retained for nonencapsulated devices after 3000 h of storage in dry air. Therefore, HPbI 3 -based one-step deposition presents a promising strategy to prepare high-performance and air-stable α-CsPbI 3 PSCs.
SUMMARY Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the pro-apoptotic molecule Daxx and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.
The device instability has been an important issue for hybrid organic-inorganic halide perovskite solar cells (PSCs). This work intends to address this issue by exploiting inorganic perovskite (CsPbBr) as light absorber, accompanied by replacing organic hole transport materials (HTM) and the metal electrode with a carbon electrode. All the fabrication processes (including those for CsPbBr and the carbon electrode) in the PSCs are conducted in ambient atmosphere. Through a systematical optimization on the fabrication processes of CsPbBr film, carbon-based PSCs (C-PSCs) obtained the highest power conversion efficiency (PCE) of about 5.0%, a relatively high value for inorganic perovskite-based PSCs. More importantly, after storage for 250 h at 80 °C, only 11.7% loss in PCE is observed for CsPbBr C-PSCs, significantly lower than that for popular CHNHPbI C-PSCs (59.0%) and other reported PSCs, which indicated a promising thermal stability of CsPbBr C-PSCs.
Both 5-methylcytosine (5mC) and its oxidized form 5-hydroxymethylcytosine (5hmC) have been proposed to be involved in tumorigenesis. Because the readout of the broadly used 5mC mapping method, bisulfite sequencing (BS-seq), is the sum of 5mC and 5hmC levels, the 5mC/5hmC patterns and relationship of these two modifications remain poorly understood. By profiling real 5mC (BS-seq corrected by Tet-assisted BS-seq, TAB-seq) and 5hmC (TAB-seq) levels simultaneously at single-nucleotide resolution, we here demonstrate that there is no global loss of 5mC in kidney tumors compared with matched normal tissues. Conversely, 5hmC was globally lost in virtually all kidney tumor tissues. The 5hmC level in tumor tissues is an independent prognostic marker for kidney cancer, with lower levels of 5hmC associated with shorter overall survival. Furthermore, we demonstrated that loss of 5hmC is linked to hypermethylation in tumors compared with matched normal tissues, particularly in gene body regions. Strikingly, gene body hypermethylation was significantly associated with silencing of the tumor-related genes. Downregulation of IDH1 was identified as a mechanism underlying 5hmC loss in kidney cancer. Restoring 5hmC levels attenuated the invasion capacity of tumor cells and suppressed tumor growth in a xenograft model. Collectively, our results demonstrate that loss of 5hmC is both a prognostic marker and an oncogenic event in kidney cancer by remodeling the DNA methylation pattern.
Since the first report in 2009, organic-inorganic hybrid perovskite solar cells (OIH-PSCs) which have achieved the power conversion efficiencies (PCEs) over 22% have gathered interest in the scientific community. Such high PCEs achieved by low-cost solution-processed fabrication techniques are comparable to the traditional commercial solar cells. However, before practical applications, the main challenge that must be addressed is material stability. Replacing organic-inorganic hybrid perovskite (OIH-PVK) with inorganic perovskites (I-PVKs) in PSCs has been a promising resolution and up to now, much progress has been made. In this review, a systematic review on the most recent research and progress in inorganic PSCs (I-PSCs) is presented, which is divided into three parts according to material category (lead-based I-PVK, lead-free I-PVK, and perovskite-derived materials). Moreover, current challenges and future research directions are suggested from the aspects of material stability, synthesis methods, device structure and working mechanism.
α-CsPbI3 with the most suitable band gap for all-inorganic perovskite solar cell (PSC) application faces an issue of phase instability at low temperature in an air atmosphere. Herein, through stoichiometric investigation, α-CsPbI3 is successfully obtained with excess CsI at 110 °C in an air atmosphere. By doping α-CsPbI3 with Sb, phase stability is further enhanced and the film morphology is also improved. Carbon-based perovskite solar cells (C-PSCs) based on CsPb0.96Sb0.04I3 achieve a promising power conversion efficiency (PCE) of 5.18%, a record value for α-CsPbI3-based PSCs without hole transport materials. Significantly, the CsPb0.96Sb0.04I3 C-PSCs retain 93% of the initial PCE after 37 days of storage in an air atmosphere. Therefore, the synergistic effect of non-stoichiometry and Sb-doping presents a promising strategy to design all-inorganic lead halide PSCs with high performance and stability.
The incidence of prostate cancer (PCa) within Asian population used to be much lower than in the Western population; however, in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly. This collaborative report summarized the latest epidemiology information, risk factors, and racial differences in PCa diagnosis, current status and new trends in surgery management and novel agents for castration-resistant prostate cancer. We believe such information would be helpful in clinical decision making for urologists and oncologists, health-care ministries and medical researchers.
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