FeOCl/MOF-derived In2S3 photocatalysts with high H2O2 adsorption: Degradation mechanism, H2O2 activation process.

The FeOCl-based photo-Fenton heterojunction catalyst holds great promise for effective water pollution treatment. A novel heterojunction FeOCl/MOF-In2S3 (F/M-I) was fabricated by coating hollow MOF-In2S3 nanoflowers onto the surface of FeOCl. Under the optimal conditions, the maximum photo-Fenton degradation rate constants of FeOCl/MOF-In2S3 for oxytetracycline (OTC) within 20 min is 0.88192 L mg-1·min-1, which are 3.2 and 2.5 times that of pure FeOCl (0.27357 L mg-1·min-1) and MOF-In2S3 (0.35222 L mg-1·min-1). Density functional theory (DFT) results confirm that the electron-rich nature of MOF-In2S3 accelerates the cycle between Fe (III)/Fe (II)of FeOCl, promoting H2O2 adsorption by FeOCl/MOF-In2S3 and generating more hydroxyl radicals (·OH) for pollutant degradation. Based on the results of DFT, combined with the results of the reactive oxidation species scavenger (ROSs), electron paramagnetic resonance (EPR) and Mott-Schottky curves, the separation and transfer behavior of photoexcited charges in FeOCl/MOF-In2S3 heterojunction and the possible photocatalytic degradation mechanism were investigated. Finally, a Z-scheme heterostructure is proposed to elucidate the catalytic mechanism. This study provides a new perspective on designing and synthesizing semiconductor materials for water treatment by photo-Fenton catalysis.

HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway.

Introduction: Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC. Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A. MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A. Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis. Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1. Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05). Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies.

FOXP4-mediated induction of PTK7 activates the Wnt/ß-catenin pathway and promotes ovarian cancer development.

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Targeted degradation of hexokinase 2 for anti­inflammatory treatment in acute lung injury.

Acute lung injury (ALI) is an acute inflammatory lung disease associated with both innate and adaptive immune responses. Hexokinase 2 (HK2) is specifically highly expressed in numerous types of inflammation­related diseases and models. In the present study in vitro and in vivo effects of targeted degradation of HK2 on ALI were explored. The degradation of HK2 by the targeting peptide TAT (transactivator of transcription protein of HIV­1)­ataxin 1 (ATXN1)­chaperone­mediated autophagy­targeting motif (CTM) was demonstrated by ELISA and western blotting in vitro and in vivo. The inhibitory effects of TAT­ATXN1­CTM on lipopolysaccharide (LPS)­induced inflammatory responses were examined using ELISAs. The therapeutic effects of TAT­ATXN1­CTM on LPS­induced ALI were examined via histological examination and ELISAs in mice. 10 µM TAT­ATXN1­CTM administration decreased HK2 protein expression and the secretion of proinflammatory cytokines (TNF­α and IL­1ß) without altering HK2 mRNA expression in LPS­treated both in vitro and in vivo, while pathological lung tissue damage and the accumulation of leukocytes, neutrophils, macrophages and lymphocytes in ALI were also significantly suppressed by 10 µM TAT­ATXN1­CTM treatment. TAT­ATXN1­CTM exhibited anti­inflammatory activity in vitro and decreased the severity of ALI in vivo. HK2 degradation may represent a novel therapeutic approach for ALI.

FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression.

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

Dynamic properties of photogenerated charge in BiOBr/Bi2WO6/GO ternary composites and its application for organic pollutants degradation.

Carbon-based Materials have been extensively researched for their prospect in the fields of environment and energy, especially for graphene oxide (GO). In this work, a novel sodium dodecyl sulfate (SDS)-assisted synthesis of BiOBr/Bi2WO6/GO ternary composite has been synthesized successfully by a handy hydrothermal method. Photoluminescence, Photocurrent, Electrochemical Impedance Spectroscopy, surface photovoltage and transient photovoltage measurements illustrate that construction of p-n BiOBr/Bi2WO6 heterojunction leads to the obviously enhancement of charge separation efficiency, and the photogenerated electrons trapped by GO can effectively inhibit the recombination process of photogenerated charge, resulting in the improvement of charge separation efficiency and the longer lifetime of photogenerated carriers for BiOBr/Bi2WO6/GO. The characterization of structure and morphology indicate that role of GO can also improve the visible light absorption range, and the SDS-assisted synthesis can reduce the size of particle in the composite and enhances the specific surface area of the composite by regulating the particle size and agglomeration. Under optimal conditions, BiOBr/Bi2WO6/GO (SDS) has the outstanding photocatalytic degradation performance and the degradation rate constants for oxytetracycline, tetracycline hydrochloride, methylene blue and rhodamine are 0.056, 0.057, 0.103 and 0.414 min-1, respectively. Notably, the degradation rate constants obtained by BiOBr/Bi2WO6/GO (SDS) are more ten times higher than that of pure BiOBr and Bi2WO6. The possible mechanism of photocatalytic degradation was suggested for BiOBr/Bi2WO6/GO based on the dynamic properties of photogenerated charge and reactive oxidation species results. Surprisingly, the recyclability of the BiOBr/Bi2WO6/GO (SDS) composite obtained from the cyclic experiments has laid a foundation for the study of efficient and stable photocatalysts.

Integrative analysis of circadian clock with prognostic and immunological biomarker identification in ovarian cancer.

Objective: To identify circadian clock (CC)-related key genes with clinical significance, providing potential biomarkers and novel insights into the CC of ovarian cancer (OC). Methods: Based on the RNA-seq profiles of OC patients in The Cancer Genome Atlas (TCGA), we explored the dysregulation and prognostic power of 12 reported CC-related genes (CCGs), which were used to generate a circadian clock index (CCI). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to identify potential hub genes. Downstream analyses including differential and survival validations were comprehensively investigated. Results: Most CCGs are abnormally expressed and significantly associated with the overall survival (OS) of OC. OC patients with a high CCI had lower OS rates. While CCI was positively related to core CCGs such as ARNTL, it also showed significant associations with immune biomarkers including CD8+ T cell infiltration, the expression of PDL1 and CTLA4, and the expression of interleukins (IL-16, NLRP3, IL-1ß, and IL-33) and steroid hormones-related genes. WGCNA screened the green gene module to be mostly correlated with CCI and CCI group, which was utilized to construct a PPI network to pick out 15 hub genes (RNF169, EDC4, CHCHD1, MRPL51, UQCC2, USP34, POM121, RPL37, SNRPC, LAMTOR5, MRPL52, LAMTOR4, NDUFB1, NDUFC1, POLR3K) related to CC. Most of them can exert prognostic values for OS of OC, and all of them were significantly associated with immune cell infiltration. Additionally, upstream regulators including transcription factors and miRNAs of key genes were predicted. Conclusion: Collectively, 15 crucial CC genes showing indicative values for prognosis and immune microenvironment of OC were comprehensively identified. These findings provided insight into the further exploration of the molecular mechanisms of OC.

USP14 regulates heme metabolism and ovarian cancer invasion through BACH1 deubiquitination and stabilization.

The deubiquitinating enzyme USP14 has been established as a crucial regulator in various diseases, including tumors, neurodegenerative diseases, and metabolic diseases, through its ability to stabilize its substrate proteins. Our group has utilized proteomic techniques to identify new potential substrate proteins for USP14, however, the underlying signaling pathways regulated by USP14 remain largely unknown. Here, we demonstrate the key role of USP14 in both heme metabolism and tumor invasion by stabilizing the protein BACH1. The cellular oxidative stress response factor NRF2 regulates antioxidant protein expression through binding to the antioxidant response element (ARE). BACH1 can compete with NRF2 for ARE binding, leading to the inhibition of the expression of antioxidant genes, including HMOX-1. Activated NRF2 also inhibits the degradation of BACH1, promoting cancer cell invasion and metastasis. Our findings showed a positive correlation between USP14 expression and NRF2 expression in various cancer tissues from the TCGA database and normal tissues from the GTEx database. Furthermore, activated NRF2 was found to increase USP14 expression in ovarian cancer (OV) cells. The overexpression of USP14 was observed to inhibit HMOX1 expression, while USP14 knockdown had the opposite effect, suggesting a role for USP14 in regulating heme metabolism. The depletion of BACH1 or inhibition of heme oxygenase 1 (coded by HMOX-1) was also found to significantly impair USP14-dependent OV cell invasion. In conclusion, our results highlight the importance of the NRF2-USP14-BACH1 axis in regulating OV cell invasion and heme metabolism, providing evidence for its potential as a therapeutic target in related diseases.

Increasing deep-water overflow from the Pacific into the South China Sea revealed by mooring observations.

Cold and dense water from the North Pacific Ocean that spills through the Luzon Strait, the only deep conduit between the South China Sea (SCS) and the Pacific Ocean, renews deep-water mass, modulates hydrographic and biogeochemical cycles, and drives abyssal and overturning circulations in the SCS. The variability of this key oceanic process, however, has been poorly studied, mainly due to a lack of sustained observations. A comprehensive observational program that started in 2009 has provided 12 years of continuous time series of velocity and volume transport within the Luzon Strait. Here we show the observation-based assessment of decadal trends of deep-water transport through this vital passage. With the estimated 12-year mean volume transport of the deep-water overflow into the SCS of 0.84 ± 0.39 Sv (1 Sv = 106 m3 s-1), a significant linear upward trend of 9% is revealed during this period. This is consistent with long-term changes in satellite-observed ocean bottom pressure. The results of this study may have broad implications for the overturning circulations and biogeochemical processes, including carbon cycles in this region.

Epigenetic reactivation of PEG3 by EZH2 inhibitors suppresses renal clear cell carcinoma progress.

PEG3 is a paternally imprinted gene located on chromosome 19q13.4 and one of the most common low-expression genes in human ovarian cancer. PEG3 plays an important role in p53-related cell death. However, whether PEG3 plays a role in renal clear cell carcinoma (ccRCC) remains unclear. Here, we found that PEG3 was epigenetic inactivated and played a tumor suppressor role in ccRCC. Overexpression of PEG3 inhibited ccRCC cell proliferation and colony formation, while removal of PEG3 significantly promoted cell proliferation in vitro and tumor formation in nude mice in vivo. EZH2-mediated H3K27me3 at the PEG3 promoter suppressed PEG3 expression. EZH2 specific inhibitors promote PEG3 transcriptional expression through the transition from H3K27me3 to H3K27ac at the PEG3 promoter region. Depletion of PEG3 inhibited the activation of the p53 signaling pathway, resulting in the resistance of ccRCC to EZH2 inhibitors treatment. Thus, our data show that EZH2-mediated epigenetic inactivation of PEG3 promotes the progress of ccRCC, and reactivation of PEG3 may be a promising strategy for ccRCC.

VHL-HIF-2α axis-induced SEMA6A upregulation stabilized ß-catenin to drive clear cell renal cell carcinoma progression.

SEMA6A is a multifunctional transmembrane semaphorin protein that participates in various cellular processes, including axon guidance, cell migration, and cancer progression. However, the role of SEMA6A in clear cell renal cell carcinoma (ccRCC) is unclear. Based on high-throughput sequencing data, here we report that SEMA6A is a novel target gene of the VHL-HIF-2α axis and overexpressed in ccRCC. Chromatin immunoprecipitation and reporter assays revealed that HIF-2α directly activated SEMA6A transcription in hypoxic ccRCC cells. Wnt/ß-catenin pathway activation is correlated with the expression of SEMA6A in ccRCC; the latter physically interacted with SEC62 and promoted ccRCC progression through SEC62-dependent ß-catenin stabilization and activation. Depletion of SEMA6A impaired HIF-2α-induced Wnt/ß-catenin pathway activation and led to defective ccRCC cell proliferation both in vitro and in vivo. SEMA6A overexpression promoted the malignant phenotypes of ccRCC, which was reversed by SEC62 depletion. Collectively, this study revealed a potential role for VHL-HIF-2α-SEMA6A-SEC62 axis in the activation of Wnt/ß-catenin pathway. Thus, SEMA6A may act as a potential therapeutic target, especially in VHL-deficient ccRCC.

Recent Advances in Inverted Perovskite Solar Cells: Designing and Fabrication.

Inverted perovskite solar cells (PSCs) have been extensively studied by reason of their negligible hysteresis effect, easy fabrication, flexible PSCs and good stability. The certified photoelectric conversion efficiency (PCE) achieved 23.5% owing to the formed lead-sulfur (Pb-S) bonds through the surface sulfidation process of perovskite film, which gradually approaches the performance of traditional upright structure PSCs and indicates their industrial application potential. However, the fabricated devices are severely affected by moisture, high temperature and ultraviolet light due to the application of organic materials. Depending on nitrogen, cost of protection may increase, especially for the industrial production in the future. In addition, the inverted PSCs are found with a series of issues compared with the traditional upright PSCs, such as nonradiative recombination of carriers, inferior stability and costly charge transport materials. Thus, the development of inverted PSCs is systematically reviewed in this paper. The design and fabrication of charge transport materials and perovskite materials, enhancement strategies (e.g., interface modification and doping) and the development of all-inorganic inverted devices are discussed to present the indicator for development of efficient and stable inverted PSCs.

Selection, Preparation and Application of Quantum Dots in Perovskite Solar Cells.

As the third generation of new thin-film solar cells, perovskite solar cells (PSCs) have attracted much attention for their excellent photovoltaic performance. Today, PSCs have reported the highest photovoltaic conversion efficiency (PCE) of 25.5%, which is an encouraging value, very close to the highest PCE of the most widely used silicon-based solar cells. However, scholars have found that PSCs have problems of being easily decomposed under ultraviolet (UV) light, poor stability, energy level mismatch and severe hysteresis, which greatly limit their industrialization. As unique materials, quantum dots (QDs) have many excellent properties and have been widely used in PSCs to address the issues mentioned above. In this article, we describe the application of various QDs as additives in different layers of PSCs, as luminescent down-shifting materials, and directly as electron transport layers (ETL), light-absorbing layers and hole transport layers (HTL). The addition of QDs optimizes the energy level arrangement within the device, expands the range of light utilization, passivates defects on the surface of the perovskite film and promotes electron and hole transport, resulting in significant improvements in both PCE and stability. We summarize in detail the role of QDs in PSCs, analyze the perspective and associated issues of QDs in PSCs, and finally offer our insights into the future direction of development.

Application of Quantum Dot Interface Modification Layer in Perovskite Solar Cells: Progress and Perspectives.

Perovskite solar cells (PSCs) are currently attracting a great deal of attention for their excellent photovoltaic properties, with a maximum photoelectric conversion efficiency (PCE) of 25.5%, comparable to that of silicon-based solar cells. However, PSCs suffer from energy level mismatch, a large number of defects in perovskite films, and easy decomposition under ultraviolet (UV) light, which greatly limit the industrial application of PSCs. Currently, quantum dot (QD) materials are widely used in PSCs due to their properties, such as quantum size effect and multi-exciton effect. In this review, we detail the application of QDs as an interfacial layer to PSCs to optimize the energy level alignment between two adjacent layers, facilitate charge and hole transport, and also effectively assist in the crystallization of perovskite films and passivate defects on the film surface.

GAS6-mediated dialogue between decidual stromal cells and macrophages is essential for early pregnancy maintenance by inducing M2-like polarization and cell proliferation of decidual macrophages.

Maternal immunotolerance towards the semi-allogeneic foetus is critical for normal pregnancy (NP). As a secretory protein, growth arrest-specific factor 6 (GAS6) promotes cancer progression by inducing the conversion of tumour-associated macrophages to an immunosuppressive M2-like phenotype. However, little is known about whether GAS6 regulates decidual macrophages (dMφs) in the early maternal-foetal interface. In this study, first-trimester decidual tissues were obtained from normal pregnant women undergoing elective terminations and patients with miscarriages. The expression of GAS6 and its receptors (AXL, TYRO3 and MERTK) in decidua and GAS6 secretion by decidual stromal cells (DSCs) was measured. Then, we investigated the effect of recombinant human GAS6 (rhGAS6) on dMφs isolated from NP and THP-1 cells, and revealed the underlying mechanism. Both the expression of GAS6 in DSCs and MERTK in dMφs, in addition to GAS6 secretion by DSCs, was found to be significantly decreased in miscarriage patients compared to that in NPs. Additionally, we observed that rhGAS6 polarized dMφs and THP-1 cells towards an M2-like phenotype, as evidenced by the up-regulated CD163 expression. Moreover, rhGAS6 enhanced the clearance of toxic cell-free haemoglobin by dMφs by up-regulating CD163 expression, and rhGAS6 also boosted cell proliferation of dMφs and THP-1 cells. Finally, we demonstrated that rhGAS6 stimulated CD163 expression and cell proliferation by activating the PI3K/Akt signalling pathway. Collectively, these findings suggest that GAS6-mediated dialogue between DSCs and dMφs is crucial for the establishment and maintenance of maternal-foetal immunotolerance, and decreased GAS6 secretion by DSCs may lead to the occurrence of miscarriage in the first trimester.

Effect of subject state on auditory brainstem response threshold using Kalman-weighted averaging.

OBJECTIVES: This study aims to explore the impact of a subject's testing state on auditory brainstem response (ABR) thresholds using a novel ABR system (Vivosonic Integrity™), which incorporates Kalman-weighted averaging and bluetooth electrical isolation to address the limitation of conventional ABR limitation to obtain a stable result under non-sedated conditions, especially for infants and children. METHOD: Twenty-four adults (18-34 years old, 48 ears) with normal hearing were enrolled for ABR testing under three different states (lying quietly in the supine position or sleeping-lying; watching silent videos quietly in a seated position-sitting; and writing in a seated position-writing), which simulate the behaviors of young children most often encountered during non-sedated Kalman-weighted ABR testing in clinical practice. The click ABR (cABR) and tone-burst ABR (tbABR) thresholds (0.5, 1, 2, and 4 kHz) of each subject and the time taken to reach the monaural threshold for each kind of stimulus were recorded. RESULTS: (1) The cABR and tbABR thresholds were observed to increase in the following order: lying < sitting < writing. Significant threshold differences were found between any two states, except for between the sitting and lying states for the cABR and between sitting and writing for the 0.5 kHz tbABR. (2) The time required for cABR testing in the writing state was significantly longer than that in the lying and sitting states. The time required for 1 and 4 kHz tbABR testing in the lying state was significantly shorter than that in the sitting or writing state. For 2 KHz tbABR, only testing time under writing was significantly longer than that under lying. There were no significant differences in the time used for 0.5 kHz tbABR testing among different states. CONCLUSIONS: Different testing states have significant impacts on the thresholds of ABRs using Kalman-weighted averaging. A subject's state during ABR testing warrants consideration, and normal levels and correction values to estimate the hearing threshold from the ABR threshold should be determined for different testing states.

Interplay of m6A and H3K27 trimethylation restrains inflammation during bacterial infection.

While N 6-methyladenosine (m6A) is the most prevalent modification of eukaryotic messenger RNA (mRNA) involved in various cellular responses, its role in modulating bacteria-induced inflammatory response remains elusive. Here, we showed that loss of the m6A reader YTH-domain family 2 (YTHDF2) promoted demethylation of histone H3 lysine-27 trimethylation (H3K27me3), which led to enhanced production of proinflammatory cytokines and facilitated the deposition of m6A cotranscriptionally. Mechanistically, the mRNA of lysine demethylase 6B (KDM6B) was m6A-modified and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote H3K27me3 demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis.

High Responsivity and External Quantum Efficiency Photodetectors Based on Solution-Processed Ni-Doped CuO Films.

Photodetectors based on p-type metal oxides are still a challenge for optoelectronic device applications. Many effects have been paid to improve their performance and expand their detection range. Here, high-quality Cu1-xNixO (x = 0, 0.2, and 0.4) film photodetectors were prepared by a solution process. The crystal quality, morphology, and grain size of Cu1-xNixO films can be modulated by Ni doping. Among the photodetectors, the Cu0.8Ni0.2O photodetector shows the maximum photocurrent value (6 × 10-7 A) under a 635 nm laser illumination. High responsivity (26.46 A/W) and external quantum efficiency (5176%) are also achieved for the Cu0.8Ni0.2O photodetector. This is because the Cu0.8Ni0.2O photosensitive layer exhibits high photoconductivity, low surface states, and high crystallization after 20% Ni doping. Compared to the other photodetectors, the Cu0.8Ni0.2O photodetector exhibits the optimal response in the near-infrared region, owing to the high absorption coefficient. These findings provide a route to fabricate high-performance and wide-detection range p-type metal oxide photodetectors.

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma.

Osteosarcoma is an aggressive malignancy with poor prognosis. Super-enhancers (SE) have been highlighted as critical oncogenic elements required for maintaining the cancer cell characteristics. However, the regulatory role of SEs in osteosarcoma properties has not yet been elucidated. In the current study, we found that osteosarcoma cells and clinical specimens shared a significant fraction of SEs. Moreover, leukemia-inhibitory factor (LIF) was identified as an essential factor under the control of osteosarcoma-specific SE. The expression of LIF was positively correlated with the stem cell core factor genes in osteosarcoma. Furthermore, LIF recombinant protein-treated osteosarcoma cells displayed enhanced stem cell-like characteristics, such as increased sphere-forming potential, stimulated self-renewal, upregulated metastasis ability, and increased stemness-related gene expression. Notably, the histone 3 lysine 27 tri-methylation (H3K27me3) demethylase UTX was found as a key activator of LIF transcription in osteosarcoma. The UTX inhibitor, GSK-J4, induced H3K27me3 accumulation and impaired histone 3 lysine 27 acetylation (H3K27ac) at LIF gene locus, leading to LIF signaling pathway inhibition. GSK-J4 treatment resulted in profound defects in stem cell-like characteristics and stemness-related gene activation in osteosarcoma by modulating the H3K27ac of NOTCH1 signaling pathway gene loci. The NOTCH1 inhibitor Crenigacestat (TargetMol, T3633) repressed LIF-mediated activation of the stemness-related genes in osteosarcoma patient-derived primary tissues. IMPLICATIONS: This study reveals osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway.

ABT737 reverses cisplatin resistance by targeting glucose metabolism of human ovarian cancer cells.

The poor prognosis and high mortality of patients with ovarian cancer result in part from their poor response to platinum-based chemotherapy. However, the precise mechanism behind cisplatin resistance is still not fully understood. In the present study, the authors explored the mechanism of resistance to cisplatin from the perspective of glucose metabolism in human ovarian cancer. The experiments using genetically matched ovarian cancer cell lines SKOV3 (cisplatin-sensitive) and SKOV3/DDP (cisplatin-resistant) in the present study provided some important findings. First, in comparison to SKOV3 cells, SKOV3/DDP cells exhibited decreased dependence on aerobic glycolysis and an increased demand for glucose. Secondly, the stable overexpression of Bcl­2 and ability to shift metabolism towards oxidative phosphorylation (OXPHOS) in SKOV3/DDP cells were associated with increased oxygen consumption. Furthermore, the metabolic characteristic of elevated OXPHOS primarily comprised most mitochondrial­derived reactive oxygen species (ROS) and, at least in part, contributed to the slight pro-oxidant state of SKOV3/DDP cells in turn. Thirdly, SKOV3/DDP cells reset the redox balance by overexpressing the key enzyme glucose 6-phosphate dehydrogenase (G6PD) of the pentose phosphate pathway to eliminate the cytotoxicity of highly elevated ROS. Furthermore, the inhibition of Bcl­2 reduced the OXPHOS and sensitivity of SKOV3/DDP cells to cisplatin in a selective manner. Furthermore, when combined with 2-deoxyglucose (2-DG), the anticancer effect of the Bcl­2 inhibitor ABT737 was greatly potentiated and hypoxia-inducible factor 1α (HIF­1α) appeared to be closely associated with Bcl­2 family members in the regulation of glucose metabolism. These results suggested that the special glucose metabolism in SKOV3/DDP cells might be selectively targeted by disrupting Bcl­2-dependent OXPHOS.