Search

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase‐like 3 (METTL3) mRNA levels were evaluated by quantitative real‐time (qRT)‐polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B‐cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual‐luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3‐mediated m6A modification. METTL3‐mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment. [ABSTRACT FROM AUTHOR]

SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain‐ and Bin/Amphiphysin/Rvs (BAR) domain‐ containing sorting nexin (SNX‐BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation‐independent mannose‐6‐phosphate receptor (CI‐MPR) from endosomes to the trans‐Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)‐stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF–EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX‐BAR proteins to mediate signaling‐coupled endolysosomal trafficking of EGFR. [ABSTRACT FROM AUTHOR]

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen. [ABSTRACT FROM AUTHOR]

Aim: The equator‐to‐poles decline in the number of species, namely the latitudinal diversity gradient (LDG), is the most conspicuous pattern in biology, yet the underlying mechanisms of this pattern remain controversial. Species dispersal could have strong effects on large‐scale species distributions but has rarely been considered in understanding the LDG. Here we sought to examine how dispersal ability may influence the latitudinal phylogenetic patterns of woody angiosperm assemblages. Location: China. Taxon: Woody angiosperms. Methods: Based on a highly supported mega‐phylogeny constructed from plastid genomes, we assessed the patterns of phylogenetic relatedness and dissimilarity of 1184 trees with three different seed dispersal modes (i.e. zoochory, anemochory and autochory) in 12 permanent forest dynamic plots covering tropical, subtropical and temperate zones in China. Results: We found that, compared with zoochorous and anemochorous species, the less vagile autochorous trees exhibited a much weaker latitudinal pattern in phylogenetic relatedness and higher phylogenetic dissimilarity among plots. The phylogenetic dissimilarity pattern of autochorous trees was explained more by geographic distance than environmental factors, consistent with a dominant role for dispersal limitation. Main Conclusions: Our study, for the first time, demonstrates that seed dispersal mode strongly influences the latitudinal phylogenetic patterns of woody angiosperm assemblages in China and highlights the importance of interaction between dispersal limitation and environmental filtering in determining the large‐scale distribution of forest biodiversity. [ABSTRACT FROM AUTHOR]

Combination immunotherapy strategies targeting OX40, a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation, differentiation, and effector function of tumor-infiltrating T cells, have attracted much attention for their excellent therapeutic effects. In this study, we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles (HBc VLPs) therapy using a mouse colon cancer model. Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody. Tumor growth was monitored. Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors. The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth, suggesting that a potent antitumor immunity was induced by the combination therapy. Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells (Teffs) and a significant decrease in regulatory T cells (Tregs) in the tumor microenvironment (TME), which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs. Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice, which may represent a potential design strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

A Cu/Pd co‐catalyzed Catellani‐type ortho arylation reaction of iodoarenes with aryl diazonium salts has been developed. Aryl radicals that derived from aryl diazonium salts were regioselectively installed at ortho position of iodoarenes via palladium catalyzed C−H activation. Mechanistic studies showed that, in contrast to classical Pd0−PdII−PdIV−PdII−Pd0 catalytic cycle, this radical cascades performed via a Pd0−PdII−PdIII−PdI−Pd0 cycle. [ABSTRACT FROM AUTHOR]

β-Ga2O3, with excellent bandgap, breakdown field, and thermal stability properties, is considered to be one of the most promising candidates for power devices including field-effect transistors (FETs) and for other applications such as Schottky barrier diodes (SBDs) and solar-blind ultraviolet photodetectors. Ohmic contact is one of the key steps in the β-Ga2O3 device fabrication process for power applications. Ohmic contact techniques have been developed in recent years, and they are summarized in this review. First, the basic theory of metal–semiconductor contact is introduced. After that, the representative literature related to Ohmic contact with β-Ga2O3 is summarized and analyzed, including the electrical properties, interface microstructure, Ohmic contact formation mechanism, and contact reliability. In addition, the promising alternative schemes, including novel annealing techniques and Au-free contact materials, which are compatible with the CMOS process, are discussed. This review will help our theoretical understanding of Ohmic contact in β-Ga2O3 devices as well as the development trends of Ohmic contact schemes. [ABSTRACT FROM AUTHOR]

Background: We performed a systematic review and meta‐analysis to investigate the links between different sleep characteristics and risk of myopia. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, PsycINFO, Wanfang, and CNKI were searched from inception to August 26, 2022, without any language restriction. Cross‐sectional, case–control, or cohort studies that explored the association between sleep duration, sleep quality, bedtime, and myopia were included. NIH quality assessment tools were used to assess the methodological quality of included studies. Random‐effect or fixed‐effect models were used to pool the associations according to whether there is heterogeneity. Results: A total of 31 studies with 205 907 participants were included in the final analysis (25 studies reporting sleep duration; four studies examining sleep quality and six studies evaluating bedtime). Compared to reference sleep duration, sufficient sleep duration (OR = 0.63, 95% CI = 0.51–0.78) was associated with a lower risk of myopia, and short sleep duration (OR = 1.66, 95% CI = 1.14–2.42) was associated with a higher risk of myopia. In addition, poor sleep quality (OR = 1.24, 95% CI = 1.05–1.47) was associated with a higher risk of myopia while late bedtime (OR = 1.30, 95% CI = 0.96–1.75) was not significantly associated with an increased risk of myopia. Conclusions: Alteration in sleep duration and sleep quality may influence the risk of myopia. Well‐designed cohort studies are needed in future investigations to identify a causal relationship between different sleep characteristics and myopia. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER)–plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER–PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER–PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca2±-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER–PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER–PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity. [ABSTRACT FROM AUTHOR]

Materials taking abundant advantage of triplet states luminescence have risen lots of attention in decades. In this work, a Cu(I) metal‐organic framework (MOF) with synchronous metal‐to‐ligand charge transfer (MLCT) state and triplet emission of the ligand is synthesized from a D–π–A–π–D ligand with suitable energy gap. The Cu(I) MOF possessed MLCT emission in the range of 450–505 nm with microsecond lifetimes (1.07 to 5.38 µs) and a triplet state emission in near infrared (NIR) region ≈705 nm with lifetimes of 1.85 ms at 300 K and 25.16 ms at 77 K, much longer than those of reported Cu(I) MOFs. Moreover, a white light is obtained through adjusting the relative intensity of dual peaks. More importantly, NIR long persistent luminescence of Cu‐MOF is observed by naked eyes under cryogenic condition. Multiple factors such as the delicate design of the D–π–A–π–D structure of ligand, the enhanced spin‐orbital coupling by Cu(I) networks, and the tight packing mode of the framework promote the generation of MLCT emission and ultralong NIR room temperature phosphorescence. The combination of calculation and experiment to analyse the luminescence mechanism of Cu(I) MOFs provides ideas for the development of Cu(I)‐based intelligently responsive materials with RTP properties. [ABSTRACT FROM AUTHOR]