Triple-junction solar cells with cyanate in ultrawide-bandgap perovskites.

Perovskite bandgap tuning without quality loss makes perovskites unique among solar absorbers, offering promising avenues for tandem solar cells1,2. However, minimizing the voltage loss when their bandgap is increased to above 1.90 eV for triple-junction tandem use is challenging3-5. Here we present a previously unknown pseudohalide, cyanate (OCN-), with a comparable effective ionic radius (1.97 Å) to bromide (1.95 Å) as a bromide substitute. Electron microscopy and X-ray scattering confirm OCN incorporation into the perovskite lattice. This contributes to notable lattice distortion, ranging from 90.5° to 96.6°, a uniform iodide-bromide distribution and consistent microstrain. Owing to these effects, OCN-based perovskite exhibits enhanced defect formation energy and substantially decreased non-radiative recombination. We achieved an inverted perovskite (1.93 eV) single-junction device with an open-circuit voltage (VOC) of 1.422 V, a VOC × FF (fill factor) product exceeding 80% of the Shockley-Queisser limit and stable performance under maximum power point tracking, culminating in a 27.62% efficiency (27.10% certified efficiency) perovskite-perovskite-silicon triple-junction solar cell with 1 cm2 aperture area.

Constructing tin oxides Interfacial Layer with Gradient Compositions for Efficient Perovskite/Silicon Tandem Solar Cells with Efficiency Exceeding 28.

Atomic layer deposition (ALD) growth of conformal thin SnOx films on perovskite absorbers offers a promising method to improve carrier-selective contacts, enable sputter processing, and prevent humidity ingress toward high-performance tandem perovskite solar cells. However, the interaction between perovskite materials and reactive ALD precursor limits the process parameters of ALD-SnOx film and requires an additional fullerene layer. Here, it demonstrates that reducing the water dose to deposit SnOx can reduce the degradation effect upon the perovskite underlayer while increasing the water dose to promote the oxidization can improve the electrical properties. Accordingly, a SnOx buffer layer with a gradient composition structure is designed, in which the compositionally varying are achieved by gradually increasing the oxygen source during the vapor deposition from the bottom to the top layer. In addition, the gradient SnOx structure with favorable energy funnels significantly enhances carrier extraction, further minimizing its dependence on the fullerene layer. Its broad applicability for different perovskite compositions and various textured morphology is demonstrated. Notably, the design boosts the efficiencies of perovskite/silicon tandem cells (1.0 cm2) on industrially textured Czochralski (CZ) silicon to a certified efficiency of 28.0%.

Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction.

This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.

Effects of Curcumin and Soy Isoflavones on Genomic Instability of Human Colon Cells NCM460 and SW620.

Curcumin (CUR) and soy isoflavones (SIs) are two plant-based polyphenols that have attracted much attention, because of their extensive anticancer and health maintenance effects. However, the relevant molecular mechanisms are still uncertain. Genomic instability (GIN) refers to a combination of gene abnormal amplification, sequence deletion, ectopic, and other types of gene damage in cells, and it is one of the main factors causing cells to lose normal physiological functions. Therefore, we used the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay as the main research method to analyze the effects of CUR and SIs on the GIN of human normal colon cells NCM460 and colon cancer cells SW620. Results show that CUR (12.5 µM) could reduce the apoptosis of NCM460 and maintain its genomic stability while inhibiting the proliferation of SW620 and promoting its apoptosis. There was no difference in the promoting effect of GIN between SW620 and NCM460 using SIs (3.125-50 µM). When the two polyphenols (v/v = 1/1, 1.5625-6.25 µM) were mixed, they could promote the proliferation and GIN of the NCM460 and SW620 cells, but we did not find that combining the two produced a better effect on the cells. In conclusion, CUR has more prominent health and anticancer effects, and it may become a dietary recommendation for daily health maintenance and a potential adjuvant drug for cancer treatment.

Photochromic Coordination Compound: Oxygen-Assisted Photoinduced Color Change for Triplet Oxygen Detection.

Detection of oxygen though color change is highly desirable for rapid qualitative analysis like the case of pH test papers. This work demonstrates 3O2-assisted photoinduced color change of a new photochromic coordination compound [Zn(4-aminopyridine)2Cl2] (ZnaPyCl), which represents the first photochromic compound with a selective 3O2 detection ability. The compound underwent photoinduced intraligand charge separation and formed a stable diradical-like triplet species in the solid state or in frozen solution, accompanied by conversion of triplet oxygen to singlet oxygen.

Broadband Photoresponsive Bismuth Halide Hybrid Semiconductors Built with π-Stacked Photoactive Polycyclic Viologen.

Photoresponse ranges of commercially prevailing photoelectric semiconductors, typically Si and InGaAs, are far from fully covering the whole solar spectrum (∼295-2500 nm), resulting in insufficient solar energy conversion or narrow wave bands for photoelectric detection. Recent studies have shown that infinite π-aggregation of viologen radicals can provide semiconductors with a photoelectric response range covering the solar spectrum. However, controlled assembly of an infinite π-aggregate is still a great challenge in material design. Through directional self-assembly of electron-transfer photoactive polycyclic ligands, two crystalline inorganic-organic hybrid photochromic viologen-based bismuth halide semiconductors, ((Me)3pytpy)[BiCl6]·2H2O [1; (Me)3pytpy = N,N',N″-trimethyl-2,4,6-tris(4-pyridyl)pyridine] and ((Me)3pytpy)[Bi2Cl9]·H2O (2), have been synthesized. They represent the first series of pytpy-based photochromic compounds. After photoinduced coloration, the conductivities of both 1 and 2 increased. The radical products have electron absorption bands in the range of 200-1600 nm, exceeding that of Si. Both the conductivity and the photocurrent intensity of 2 are stronger than those of 1, due to better planarity, tighter π-stacking, and higher degrees of overlap of ((Me)3pytpy)3+ cations. This study not only provides a new design idea for synthesizing radical-based multispectral photoelectric semiconductors but also enriches the family of electron-transfer photochromic compounds.

Effects of strong interactions between Ti and ceria on the structures of Ti/CeO2.

The effects of strong interactions between Ti and ceria on the structures of Ti/CeO2(111) are systematically investigated by density functional theory calculation. To our best knowledge, the adsorption energy of a Ti atom at the hollow site of CeO2 is the highest value (-7.99 eV) reported in the literature compared with those of Au (-0.88--1.26 eV), Ag (-1.42 eV), Cu (-2.69 eV), Pd (-1.75 eV), Pt (-2.62 eV) and Sn (-3.68 eV). It is very interesting to find that Ti adatoms disperse at the hollow site of CeO2(111) to form surface TiOx species, instead of aggregating to form Ti metal clusters for the Ti-CeO2 interactions that are much stronger than those of Ti-Ti ones. Ti adatoms are completely oxidized to Ti4+ ions if they are monatomically dispersed on the next near hollow sites of CeO2(111) (xTi-NN-hollow); while Ti3+ ions are observed when they locate at the near hollow sites (xTi-N-hollow). Due to the electronic repulsive effects among Ti3+ ions, the adsorption energies of xTi-N-hollow are slightly weaker than those of xTi-NN-hollow. Simultaneously, the existence of unstable Ti3+ ions on xTi-N-hollow also leads to the restructuring of xTi-N-hollow by surface O atoms of ceria transferring to the top of Ti3+ ions, or oxidation by O2 adsorption and dissociation. Both processes improve the stability of the xTi/CeO2 system by Ti3+ oxidation. Correspondingly, surface TiO2-like species form. This work sheds light into the structures of metal/CeO2 catalysts with strong interactions between the metal and the ceria support.

Metabolomics beyond spectroscopic databases: a combined MS/NMR strategy for the rapid identification of new metabolites in complex mixtures.

A novel strategy is introduced that combines high-resolution mass spectrometry (MS) with NMR for the identification of unknown components in complex metabolite mixtures encountered in metabolomics. The approach first identifies the chemical formulas of the mixture components from accurate masses by MS and then generates all feasible structures (structural manifold) that are consistent with these chemical formulas. Next, NMR spectra of each member of the structural manifold are predicted and compared with the experimental NMR spectra in order to identify the molecular structures that match the information obtained from both the MS and NMR techniques. This combined MS/NMR approach was applied to Escherichia coli extract, where the approach correctly identified a wide range of different types of metabolites, including amino acids, nucleic acids, polyamines, nucleosides, and carbohydrate conjugates. This makes this approach, which is termed SUMMIT MS/NMR, well suited for high-throughput applications for the discovery of new metabolites in biological and biomedical mixtures, overcoming the need of experimental MS and NMR metabolite databases.

Assembly of Bazooka polarity landmarks through a multifaceted membrane-association mechanism.

Epithelial cell polarity is essential for animal development. The scaffold protein Bazooka (Baz/PAR-3) forms apical polarity landmarks to organize epithelial cells. However, it is unclear how Baz is recruited to the plasma membrane and how this is coupled with downstream effects. Baz contains an oligomerization domain, three PDZ domains, and binding regions for the protein kinase aPKC and phosphoinositide lipids. With a structure-function approach, we dissected the roles of these domains in the localization and function of Baz in the Drosophila embryonic ectoderm. We found that a multifaceted membrane association mechanism localizes Baz to the apical circumference. Although none of the Baz protein domains are essential for cortical localization, we determined that each contributes to cortical anchorage in a specific manner. We propose that the redundancies involved might provide plasticity and robustness to Baz polarity landmarks. We also identified specific downstream effects, including the promotion of epithelial structure, a positive-feedback loop that recruits aPKC, PAR-6 and Crumbs, and a negative-feedback loop that regulates Baz.

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma.

INTRODUCTION: Nuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC. METHODS: We performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin-forming cells (HaCaT) and human cSCC cells (A431, Colo-16, SCL-1, SCL-2, and HSC-5). Stable A431 and SCL-2 cell lines consisting of sh-RNA-NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/ß-catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK-8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown. RESULTS: NR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/ß-catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin. CONCLUSION: NR5A2 plays a crucial role in the progression of cSCC, and the Wnt/ß-catenin signaling pathway may be involved in the regulation of NR5A2-mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.

PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

Evaluation and comparison of physicochemical properties, volatile substances, and microbial communities of leaf mustard (Brassica juncea var. multiceps) under natural and inoculated fermentation.

Due to the uncontrolled fermentation process and unstable quality of naturally fermented leaf mustard, inoculated fermentation is receiving more attention. Here, the physicochemical properties, volatile compounds, and microbial community in leaf mustard under natural fermentation (NF) and inoculated fermentation (IF) were analyzed and compared. The contents of total acid, crude fiber, and nitrite of leaf mustard were measured. Headspace-solid phase microextraction-gas chromatography-mass spectrometry and orthogonal projection on latent structure-discriminant analysis were used to analyze the differences of volatile compounds in NF and IF leaf mustard. Moreover, Illumina MiSeq high-throughput sequencing technology was employed to reveal the composition of microbiota. The results showed that the nitrite content in leaf mustard after IF (3.69 mg/kg) was significantly lower than that after NF (4.43 mg/kg). A total of 31 and 25 kinds of volatile components were identified in IF and NF, respectively. Among the detected compounds, 11 compounds caused the differences between IF and NF leaf mustard. The results of inter-group difference analysis showed that there were significant differences in fungal flora between IF and NF samples. Saccharomycetes, Kazachstania, and Ascomycota were the landmark microorganisms in IF leaf mustard and the landmark microorganisms in NF were Mortierellomycota, Sordariomycetes, and Eurotiomycetes. The abundance of probiotics (such as Lactobacillus) in IF leaf mustard (51.22%) was higher than that in NF (35.20%) and the abundance of harmful molds (such as Mortierella and Aspergillus) was opposite. Therefore, IF leaf mustard showed the potential to reduce the content of nitrite and harmful molds and increase the beneficial volatile compounds and probiotics. PRACTICAL APPLICATION: Leaf mustard of inoculated fermentation (IF) showed better fermented characteristics than natural fermentation in terms of lower nitrite content, greater beneficial volatile substances, and better potential for increasing probiotics and reducing harmful molds. These results provided a theoretical basis for IF leaf mustard and contributed to the industrial production of fermented leaf mustard.

Guilingji capsule for Alzheimer's disease: secondary analysis of a randomized non-inferiority controlled trial.

OBJECTIVE: To investigate the effectiveness and safety of Guilingji capsule (, GLJC) in treatment of Alzheimer's disease (AD) patients with kidney-marrow deficiency pattern (KMDP) compared with gingko extract tablets. METHODS: This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial. A total of 120 AD patients with KMDP were enrolled in this study. The participants were randomly categorized into two groups: (a) GLJC group ( = 60) and (b) gingko group ( = 60). The GLJC group was treated with GLJC and gingko extract mimetic tablets, whereas the gingko group received gingko extract tablets and mimetic GLJC. The data on the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Activities of Daily Living (ADL), and Chinese Medicine Symptom Scale (CM-SS) was evaluated at 0, 12, and 24 weeks of treatment. The serum levels of acetylcholine (Ach), acetylcholinesterase (AchE), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the participants were measured before and after 24 weeks of treatment. The safety was based on the incidence of adverse events. RESULTS: Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog, ADL, and CM-SS scores ( < 0.01). Compared with the gingko group, the GLJC group had a higher effective rate of improvement in the symptoms of "amnesia" and "dull expression and slow thinking" at the 12th week and 24th week ( < 0.05, < 0.01). In the GLJC group, serum Bcl-2 levels were significantly increased at the 24th week ( < 0.05). Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week ( < 0.01). No treatment-related adverse events were reported in the two groups. CONCLUSIONS: GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety. When it comes to improving TCM symptoms and anti-aging, GLJC is even more advantageous.

Investigating the active chemical constituents and pharmacology of Nanocnide lobata in the treatment of burn and scald injuries.

OBJECTIVE: To identify the most effective fraction of Nanocnide lobata in the treatment of burn and scald injuries and determine its bioactive constituents. METHODS: Chemical identification methods were used to analyze solutions extracted from Nanocnide lobata using petroleum ether, ethyl acetate, n-butanol using a variety of color reactions. The chemical constituents of the extracts were identified by ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS). A total of 60 female mice were randomly divided into the following 6 groups: the petroleum ether extract-treated group; the ethyl acetate extract-treated group; the n-butanol extract-treated group; the model group; the control group; and the positive drug group. The burn/scald model was established using Stevenson's method. At 24 hours after modeling, 0.1 g of the corresponding ointment was evenly applied to the wound in each group. Mice in the model group did not undergo treatment, while those in the control group received 0.1 g of Vaseline. Wound characteristics, including color, secretions, hardness, and swelling, were observed and recorded. Photos were taken and the wound area calculated on the 1st, 5th, 8th, 12th, 15th, 18th and 21st days. Hematoxylin-eosin (HE) staining was utilized to observe the wound tissue of mice on the 7th, 14th, and 21st days. An enzyme-linked immunosorbent assay (ELISA) kit was used to measure the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1. RESULTS: The chemical constituents of Nanocnide lobata mainly include volatile oils, coumarins, and lactones. UPLC-MS analysis revealed 39 main compounds in the Nanocnide lobata extract. Among them, ferulic acid, kaempferitrin, caffeic acid, and salicylic acid have been confirmed to exhibit anti-inflammatory and antioxidant activity related to the treatment of burns and scalds. HE staining revealed a gradual decrease in the number of inflammatory cells and healing of the wounds with increasing time after Nanocnide lobata extract administration. Compared with the model group, the petroleum ether extract-treated group showed significant differences in the levels of TNF-α (161.67±4.93, 106.33±3.21, 77.67±4.04 pg/mL) and IL-10 (291.77±4.93, 185.09±9.54, 141.33±1.53 pg/mL) on the 7th, 14th, and 21st days; a significant difference in the content of TGF-ß1 (75.68±3.06 pg/mL) on the 21st day; and a significant difference in the level of VEGF (266.67±4.73, 311.33±10.50 pg/mL) on the 7th and 14th days respectively. CONCLUSION: Petroleum ether Nanocnide lobata extract and the volatile oil compounds of Nanocnide lobata might be effective drugs in the treatment of burn and scald injuries, as they exhibited a protective effect on burns and scalds by reducing the expression of TNF-α, IL-10 and TGF-ß1 and increasing the expression of VEGF. In addition, these compounds may also exert pharmacological effects that promote wound tissue repair, accelerate wound healing, and reduce scar tissue proliferation, inflammation and pain.

Colored Silicon Heterojunction Solar Cells Exceeding 23.5% Efficiency Enabled by Luminescent Down-Shift Quantum Dots.

Colored solar panels, realized by depositing various reflection layers or structures, are emerging as power sources for building with visual aesthetics. However, these panels suffer from reduced photocurrent generation due to the less efficient light harvesting from visible light reflection and degraded power conversion efficiency (PCE). Here, color-patterned silicon heterojunction solar cells are achieved by incorporating luminescent quantum dots (QDs) with high quantum yields as light converters to realize an asthenic appearance with high PCE. It is found that large bandgap (blue) QD layers can convert UV light into visible light, which can notably alleviate the parasitic absorption by the front indium tin oxide and doped amorphous silicon. Additionally, a universal optical path model is proposed to understand the light transmission process, which is suitable for luminescent down-shift devices. In this study, solar cells with a PCE exceeding 23.5% are achieved using the combination of a blue QD layer and a top low refractive index anti-reflection layer. Based on our best knoledge,the obtained PCE is the highest for a color-patterned solar cell. The results suggest an enhanced strategy involving incorporation of luminescent QDs with an optical path design for high-performance photovoltaic panels with visual aesthetics.

Buried-Interface Engineering of Conformal 2D/3D Perovskite Heterojunction for Efficient Perovskite/Silicon Tandem Solar Cells on Industrially Textured Silicon.

Exploring strategies to control the crystallization and modulate interfacial properties for high-quality perovskite film on industry-relevant textured crystalline silicon solar cells is highly valued in the perovskite/silicon tandem photovoltaics community. The formation of a 2D/3D perovskite heterojunction is widely employed to passivate defects and suppress ion migration in the film surface of perovskite solar cells. However, realizing solution-processed heterostructures at the buried interface faces solvent incompatibilities with the challenge of underlying-layer disruption, and texture incompatibilities with the challenge of uneven coverage. Here, a hybrid two-step deposition method is used to prepare robust 2D perovskites with cross-linkable ligands underneath the 3D perovskite. This structurally coherent interlayer benefits by way of preferred crystal growth of strain-free and uniform upper perovskite, inhibits interfacial defect-induced instability and recombination, and promotes charge-carrier extraction with ideal energy-level alignment. The broad applicability of the bottom-contact heterostructure for different textured substrates with conformal coverage and various precursor solutions with intact properties free of erosion are demonstrated. With this buried interface engineering strategy, the resulting perovskite/silicon tandem cells, based on industrially textured Czochralski (CZ) silicon, achieve a certified efficiency of 28.4% (1.0 cm2 ), while retaining 89% of the initial PCE after over 1000 h operation.

Heat shock factor 1 regulates the expression of the TRPV1 gene in the rat preoptic-anterior hypothalamus area during lipopolysaccharide-induced fever.

The TRPV1 cation channel is a member of the thermo-TRP family of ionic channels activated by noxious heat and various endogenous mediators. Expression of TRPV1 is widespread and includes hypothalamic neurons. The preoptic-anterior hypothalamus area (PO/AH) are required for regulation of body temperature, suggesting that resident thermosensitive TRPV1 channels may be involved in thermoregulation. Heat shock factor 1 (HSF1) is a ubiquitous heat-sensitive transcription factor that co-ordinates the genomic response to noxious heat, but it is not known whether TRPV1 expression is part of this adaptive mechanism. We therefore investigated whether HSF1 regulates TRPV1 transcription in response to lipopolysaccharide (LPS)-induced fever in rats. Expression of TRPV1 and nuclear translocation of HSF1 were transiently upregulated during LPS-induced fever, with temporal profiles that mirrored the rise and fall in body temperature. We used a series of luciferase reporter vectors encoding different spans of the TRPV1 gene 5'-flanking region to identify possible HSF1-binding sites. Reporter assays in transfected PC12 cells demonstrated that only TRPV1 promoters with the -1160 to -821 region drove reporter expression in response to heat shock. This region contains one putative heat shock-responsive element (HSE) for HSF1 binding at -919 to -910. Site-directed mutagenesis of this HSE abrogated reporter activity in response to heat shock, indicating that -919 to -910 contains the specific HSF1-binding sequence. In the PO/AH, electrophoretic mobility shift assay and chromatin immunoprecipitation assay analyses demonstrated that HSF1 is recruited to the HSE of the TRPV1 gene in PO/AH cells during LPS-induced fever, resulting in enhanced TRPV1 expression. Based on these findings, we conclude that HSF1 regulates TRPV1 gene expression in PO/AH of rats with LPS-induced fever.

Association of nitrogen compounds in drinking water with incidence of esophageal squamous cell carcinoma in Shexian, China.

The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth most common malignancy worldwide, is highest in China. The purpose of this study was to investigate the association between nitrogen compounds in drinking water with the incidence of ESCC by geographical spatial analysis. The incidence of ESCC is high in Shexian county, China, and environmental factors, particularly nitrogen-contaminated drinking water, are the main suspected risk factors. This study focuses on three nitrogen compounds in drinking water, namely, nitrates, nitrites, and ammonia, all of which are derived mainly from domestic garbage and agricultural fertilizer. The study surveyed 48 villages in the Shexian area with a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer subjects). Hot-spot analysis was used to identify spatial clusters with a high incidence of ESCC and a high concentration of nitrogen compounds. Logistic regression analysis was used to detect risk factors for ESCC incidence. Most areas with high concentrations of nitrate nitrogen in drinking water had a high incidence of ESCC. Correlation analysis revealed a significant positive relationship between nitrate concentration and ESCC (P = 0.01). Logistic regression analysis also confirmed that nitrate nitrogen has a significantly higher odds ratio. The results indicate that nitrate nitrogen is associated with ESCC incidence in Shexian county. In conclusion, high concentrations of nitrate nitrogen in drinking water may be a significant risk factor for the incidence of ESCC.

Polymorphisms in ERCC4 and ERCC5 and risk of cancers: Systematic research synopsis, meta-analysis, and epidemiological evidence.

The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision repair pathway, ERCC4 and ERCC5 polymorphisms are linked with susceptibility to multiple cancers, but the conclusions were controversial. In this updated meta-analysis concerned with ERCC4 and ERCC5 single-nucleotide polymorphisms (SNPs), 160 eligible publications were identified, and we exerted the meta-analysis of correlations between 24 variants and 19 types of cancer. Venice criteria and the false-positive report probability were used to evaluate a cumulative evidence of significant associations. We conducted functional annotations for those strong associations using data from the Encyclopedia of DNA Elements (ENCODE) Project. We obtained 11 polymorphisms significantly related to changed susceptibility to 11 cancers (p < 0.05). Strong evidence was assigned to four variant-related cancer risks in Asians (ERCC4 rs744154 with bladder cancer, ERCC5 rs2296147 with esophageal cancer, ERCC5 rs17655 with laryngeal cancer and uterine cancer, and ERCC5 rs751402 with gastric cancer), moderate to six SNPs with a risk of eight cancers, and weak to nine SNPs with nine cancers. Data from ENCODE and other public databases showed that the loci of these SNPs with strong evidence might fall in putative functional regions. In conclusion, this paper summarizes comprehensive evidence that common variants of ERCC4 and ERCC5 genes are strongly associated with the risk of bladder cancer, esophageal cancer, laryngeal cancer, uterine cancer, and gastric cancer and elucidates the crucial role of the DNA repair genes in the genetic predisposition to human cancers.