Causal association of immune cells and endometriosis: a Mendelian randomization study.

Objective: To investigate the causal effect of immune cells on endometriosis (EMS), we performed a Mendelian randomization analysis. Methods: Mendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effects of exposures on outcomes in observational data. In this study, we conducted a thorough two-sample MR analysis to investigate the causal relationship between 731 immune cells and endometriosis. We used complementary Mendelian randomization (MR) methods, including weighted median estimator (WME) and inverse variance weighted (IVW), and performed sensitivity analyses to assess the robustness of our results. Results: Four immune phenotypes have been found to be significantly associated with the risk of developing EMS: B cell %lymphocyte (WME: OR: 1.074, p = 0.027 and IVW: OR: 1.058, p = 0.008), CD14 on Mo MDSC (WME: OR: 1.056, p =0.021 and IVW: OR: 1.047, p = 0.021), CD14+ CD16- monocyte %monocyte (WME: OR: 0.947, p = 0.024 and IVW: OR: 0.958, p = 0.011), CD25 on unsw mem (WME: OR: 1.055, p = 0.030 and IVW: OR: 1.048, p = 0.003). Sensitivity analyses confirmed the main findings, demonstrating consistency across analyses. Conclusions: Our MR analysis provides compelling evidence for a direct causal link between immune cells and EMS, thereby advancing our understanding of the disease. It also provides new avenues and opportunities for the development of immunomodulatory therapeutic strategies in the future.

Creating CoRu Dual Active Sites Codecorated Stable Porous Ceria Support for Enhanced Li-CO2 Batteries Cathodes.

Lithium-carbon dioxide (Li-CO2) battery represents a high-energy density energy storage with excellent real-time CO2 enrichment and conversion, but its practical utilization is hampered by the development of an excellent catalytic cathode. Here, the synergistic catalytic strategy of designing CoRu bimetallic active sites achieves the electrocatalytic conversion of CO2 and the efficient decomposition of the discharge products, which in turn realizes the smooth operation of the Li-CO2 battery. Moreover, obtained support based on metal-organic frameworks precursors facilitates the convenient diffusion and adsorption of CO2, resulting in higher reaction concentration and lower mass transfer resistance. Meanwhile, the optimization of the interfacial electronic structure and the effective transfer of electrons are achieved by virtue of the strong interaction of CoRu at the support interface. As a result, the Li-CO2 cell assembled based on bimetallic CoRu active sites achieved a discharge capacity of 19,111 mA h g-1 and a steady-state discharge voltage of 2.58 V as well as a cycle life of >175 cycles at a rate of 100 mA g-1. Further experiments combined with density-functional theory calculations achieve a deeply view of the connection between cathode and electrochemical performance and pave a way for the subsequent development of advanced Li-CO2 catalytic cathodes.

Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study.

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

One-Stone-for-Two-Birds Strategy for VSe2 to Enable High Capacity and Long-Life Zinc Storage.

Based on a specific zinc storage mechanism and excellent electronic conductivity, transition metal dichalcogenides, represented by vanadium diselenide, are widely used in aqueous zinc-ion battery (AZIB) energy storage systems. However, most vanadium diselenide cathode materials are presently limited by low specific capacity and poor cycling life. Herein, a simple hydrothermal process has been proposed for obtaining a vanadium diselenide cathode for an AZIB. The interaction of defects and crystal planes enhances zinc storage capacity and reduces the migration energy barrier. Moreover, abundant lamellar structure greatly increases reaction sites and alleviates volume expansion during the electrochemical process. Thus, the as-obtained vanadium diselenide AZIB exhibits an excellent reversible specific capacity of 377 mAh g-1 at 1 A g-1, and ultralong cycle stability of 291 mAh g-1 after 3200 cycles, with a nearly negligible capacity loss. This one-stone-for-two-birds strategy would be expected to be applied to large-scale synthesis of a high-performance zinc-ion battery cathode in the future.

Unique Hierarchically Structured High-Entropy Alloys with Multiple Adsorption Sites for Rechargeable Li-CO2 Batteries with High Capacity.

Lithium-carbon dioxide (Li-CO2) batteries offer the possibility of synchronous implementation of carbon neutrality and the development of advanced energy storage devices. The exploration of low-cost and efficient cathode catalysts is key to the improvement of Li-CO2 batteries. Herein, high-entropy alloys (HEAs)@C hierarchical nanosheet is synthesized from the simulation of the recycling solution of waste batteries to construct a cathode for the first time. Owing to the excellent electrical conductivity of the carbon material, the unique high-entropy effect of the HEAs, and the large number of catalytically active sites exposed by the hierarchical structure, the FeCoNiMnCuAl@C-based battery exhibits a superior discharge capability of 27664 mAh g-1 and outstanding durability of 134 cycles as well as low overpotential with 1.05 V at a discharge/recharge rate of 100 mA g-1. The adsorption capacity of different sites on the HEAs is deeply understood through density functional theory calculations combined with experiments. This work opens up the application of HEAs in Li-CO2 batteries catalytic cathodes and provides unique insights into the study of adsorption active sites in HEAs.

Predicting radiation pneumonitis in lung cancer: a EUD-based machine learning approach for volumetric modulated arc therapy patients.

Purpose: This study aims to develop an optimal machine learning model that uses lung equivalent uniform dose (lung EUD to predict radiation pneumonitis (RP) occurrence in lung cancer patients treated with volumetric modulated arc therapy (VMAT). Methods: We analyzed a cohort of 77 patients diagnosed with locally advanced squamous cell lung cancer (LASCLC) receiving concurrent chemoradiotherapy with VMAT. Patients were categorized based on the onset of grade II or higher radiation pneumonitis (RP 2+). Dose volume histogram data, extracted from the treatment planning system, were used to compute the lung EUD values for both groups using a specialized numerical analysis code. We identified the parameter α, representing the most significant relative difference in lung EUD between the two groups. The predictive potential of variables for RP2+, including physical dose metrics, lung EUD, normal tissue complication probability (NTCP) from the Lyman-Kutcher-Burman (LKB) model, and lung EUD-calibrated NTCP for affected and whole lung, underwent both univariate and multivariate analyses. Relevant variables were then employed as inputs for machine learning models: multiple logistic regression (MLR), support vector machine (SVM), decision tree (DT), and K-nearest neighbor (KNN). Each model's performance was gauged using the area under the curve (AUC), determining the best-performing model. Results: The optimal α-value for lung EUD was 0.3, maximizing the relative lung EUD difference between the RP 2+ and non-RP 2+ groups. A strong correlation coefficient of 0.929 (P< 0.01) was observed between lung EUD (α = 0.3) and physical dose metrics. When examining predictive capabilities, lung EUD-based NTCP for the affected lung (AUC: 0.862) and whole lung (AUC: 0.815) surpassed LKB-based NTCP for the respective lungs. The decision tree (DT) model using lung EUD-based predictors emerged as the superior model, achieving an AUC of 0.98 in both training and validation datasets. Discussions: The likelihood of developing RP 2+ has shown a significant correlation with the advancements in RT technology. From traditional 3-D conformal RT, lung cancer treatment methodologies have transitioned to sophisticated techniques like static IMRT. Accurately deriving such a dose-effect relationship through NTCP modeling of RP incidence is statistically challenging due to the increased number of degrees-of-freedom. To the best of our knowledge, many studies have not clarified the rationale behind setting the α-value to 0.99 or 1, despite the closely aligned calculated lung EUD and lung mean dose MLD. Perfect independence among variables is rarely achievable in real-world scenarios. Four prominent machine learning algorithms were used to devise our prediction models. The inclusion of lung EUD-based factors substantially enhanced their predictive performance for RP 2+. Our results advocate for the decision tree model with lung EUD-based predictors as the optimal prediction tool for VMAT-treated lung cancer patients. Which could replace conventional dosimetric parameters, potentially simplifying complex neural network structures in prediction models.

Revealing the construction of CuOCe interfacial sites via increased support utilization for enhanced CO2 electroreduction and Li-CO2 batteries.

Leveraging designed electronic oxide-metal interactions (EOMI), cerium-supported copper demonstrates remarkable competitiveness in the carbon dioxide reduction reaction (CO2RR). Nevertheless, the limited utilization efficiency of conventional cerium oxide (CeO2) support hampers the EOMI effect. Furthermore, a comprehensive understanding of the influence of distinct crystalline surfaces of CeO2 on the loaded active copper (Cu) species remains elusive. Herein, oxide carriers with diverse crystal facets are acquire for loading to load Cu species through the incorporation of cerium-based metal organic frameworks (MOFs) precursors. Simultaneously, owing to the elevated specific surface area conferred by MOF precursors, Cu/CeO2 hosts ample catalytically active sites for carbon dioxide (CO2) electrocatalytic reactions and as catalytic cathodes for lithium-CO2 (Li-CO2) batteries. Furthermore, the carbon converted from organic ligands in MOFs precursors not only proficiently immobilizes and disperses the active sites, but also enhances the inherent conductive stability of the oxide while augmenting energy utilization efficiency. Leveraging these advantages, the electrocatalyst derived from MOFs achieves a peak CO2-to-methane Faradaic efficiency of 57.9 %, whereas the assembled Li-CO2 batteries exhibit notable activity and durability, boasting a substantial full-discharge capacity of 8907 mAh/g, a discharge voltage of 2.65 V, and an extended cycle life exceeding 1000 h. Mechanistic investigations were conducted using density functional theory (DFT) calculations to thoroughly explore the impact of CeO2 carrier crystal facets, specifically (111), (100), and (110), on the loaded copper species. Notably, (110) was identified as the optimal facet due to its favorable contributions to electronic structure optimization and stability enhancement.

Resveratrol reverses Palmitic Acid-induced cow neutrophils apoptosis through shifting glucose metabolism into lipid metabolism via Cav-1/ CPT 1-mediated FAO enhancement.

Elevated plasma nonesterified fatty acids (NEFAs) affect neutrophils function and longevity during the periparturient period in dairy cows. Previous research has shown that resveratrol (RSV) may protect cell viability from NEFA-induced damage by regulating energy metabolism. However, it is unclear whether RSV has a protective effect on palmitic acid (PA)-treated neutrophils. The aim of this study was to investigate the molecular regulatory mechanism of the protective effect of RSV on neutrophils. The results showed that treatment with high concentrations of RSV (50 µM, 100 µM) maintained neutrophils activity by inhibiting neutrophils apoptosis (P < 0.05). Further analysis showed that high concentrations of RSV enhanced fatty acid oxidation (FAO) to produce ATP by promoting the expression of CAV1, ACSL-1 and CPT1 (P < 0. 05) while inhibiting glycolysis by suppressing PFK1 activity (P < 0. 05) and reducing glucose transport-related protein (GLUT1/GLUT4) expression by inhibiting glucose uptake (P < 0.05). These results suggest that RSV protects neutrophils from PA-induced apoptosis by regulating energy metabolism. Our results revealed that RSV protects neutrophils from PA-induced apoptosis by shifting glucose metabolism to lipid metabolism. This study tenders to a meaningful understanding of the effects of RSV on neutrophils function in periparturient cows suffering from negative energy balance (NEB).

One-Pot synthesis of flavones catalyzed by an Au-mediated covalent organic framework.

Covalent organic frameworks (COFs) are excellent candidates for rationally designed metal-coordinated catalysts due to their porous structures and adjustable organic building blocks. In this work, a two-dimensional (2D) COF with novel fxt topology was synthesized. The newly devised COF had been fully characterized by a range of spectroscopic and microscopic techniques. The COF was further metallized by the gold species to form a heterogeneous catalyst that enabled the one-pot synthesis of flavone and its derivatives. The Au@COF catalyst showed high catalytic activity and good recyclability. This work demonstrates the great potential of metallized COFs with unique well-defined pores in organic catalysis.

Synthesis of a Novel Spherical-Shell-Structure Polymerized Ionic Liquid Microsphere PILM/Au/Al(OH)3 Catalyst for Benzyl Alcohol Oxidation.

In order to selectively oxidize benzyl alcohol, a novel noble metal catalyst based on polymer ionic liquids with a core-shell structure was created. First, polymer ionic liquid microspheres (PILMs) were prepared by free radical polymerization. Second, the in situ adsorption of Au nanoparticles on the surface of PILMs was accomplished, thanks to the strong electrostatic interaction between N atoms and metal ions on the diazole ring of PILMs. Additionally, the introduction of Al(OH)3 prevented the aggregation of Au nanoparticles and promoted the catalytic reaction. Finally, the PILM/Au/Al(OH)3 catalyst with a core-shell structure was formed. The effectiveness of the PILM/Au/Al(OH)3 catalyst was assessed by varying the catalyst's type, quantity, amount of Au, amount of H2O2, temperature, and reaction time. After five cycles of experiments, the catalyst was effective and reusable. In addition, the potential catalytic mechanism of the catalyst in the oxidation of benzyl alcohol was proposed.

Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer.

Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/ß-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/ß-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a ß-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.

Reaction Site Designation by Intramolecular Electric Field in Tröger's-Base-Derived Conjugated Microporous Polymer for Near-Unity Selectivity of CO2 Photoconversion.

To facilitate solar-driven overall CO2 and H2 O convsersion into fuels and O2 , a series of covalent microporous polymers derived from Tröger's base are synthesized featuring flexural backbone and unusual charge-transfer properties. The incorporation of rigid structural twist Tröger's base unit grants the polymers enhanced microporosity and CO2 adsorption/activation capacity. Density function theory calculations and photo-electrochemical analyses reveal that an electric dipole moment (from negative to positive) directed to the Tröger's base unit is formed across two obliquely opposed molecular fragments and induces an intramolecular electric field. The Tröger's base unit located at folding point becomes an electron trap to attract photogenerated electrons in the molecular network, which brings about suppression of carrier recombination and designates the reaction site in synergy with the conjugated network. In response to the discrepancy in reaction pathways across the reaction sites, the product allocation in the catalytic reaction is thereby regulated. Optimally, CMP-nTB achieves the highest photocatalytic CO production of 163.53 µmol g-1 h-1 with approximately unity selectivity, along with H2 O oxidation to O2 in the absence of any photosensitizer or co-catalyst. This work provides new insight for developing specialized artificial organic photocatalysts.

Pendant Length-Dependent Electrochemical Performances for Conjugated Organic Polymers as Solid-State Polymer Electrolytes in Lithium Metal Batteries.

The development of solid-state polymer electrolytes (SPEs) has been plagued by poor ionic conductivity, low ionic transference number, and limited electrochemical potential window. The exploitation of ionized SPEs is a feasible avenue to solve this problem. Herein, conjugated organic polymers (COPs) with excellent designability and rich pore structures have been selected as platforms for exploration. Three cationic COPs with different chain lengths of quaternary ammonium salts (CbzT@Cx, x = 4, 6, 9) are designed and applied to SPEs for the first time. Meanwhile, the effects of chain lengths on their electrochemical performances are compared. Especially, CbzT@C9 shows the most attractive electrochemical performance due to its high specific surface area of 212.3 m2 g-1. The larger specific surface area allows more exposure of the long-chain quaternary ammonium cation groups, which is more favorable for the dissociation of lithium salts. Moreover, the flexible long-chain structure increases the compatibility with poly(ethylene oxide) (PEO) and reduces the crystallinity of PEO to some extent. The richer pore structure can accommodate more PEO, further disrupting the crystallinity of PEO and creating more channels for the ether-oxygen chain to transport lithium ions. At 60 °C, the SPE (CbzTM@C9) presents an excellent ionic conductivity (σ) of 8.00 × 10-4 S cm-1. CbzTM@C9 has a lithium-ion transference number (tLi+) of 0.48. Thus, the assembled Li/CbzTM@C9/LiFePO4 battery provides a good discharge capacity of 158.8 mAh g-1 at 0.1C. After 70 cycles, the capacity retention rate is 93.8% with a Coulombic efficiency of 98%. The excellent flexibility brings stable power supply capability under various bending angles to the assembled Li/CbzTM@C9/LiFePO4 soft-packed battery. The project uses conjugated organic polymers in SPEs and creates an avenue to develop flexible energy storage equipment.

Prediction of radiation-induced acute skin toxicity in breast cancer patients using data encapsulation screening and dose-gradient-based multi-region radiomics technique: A multicenter study.

Purpose: Radiation-induced dermatitis is one of the most common side effects for breast cancer patients treated with radiation therapy (RT). Acute complications can have a considerable impact on tumor control and quality of life for breast cancer patients. In this study, we aimed to develop a novel quantitative high-accuracy machine learning tool for prediction of radiation-induced dermatitis (grade ≥ 2) (RD 2+) before RT by using data encapsulation screening and multi-region dose-gradient-based radiomics techniques, based on the pre-treatment planning computed tomography (CT) images, clinical and dosimetric information of breast cancer patients. Methods and Materials: 214 patients with breast cancer who underwent RT between 2018 and 2021 were retrospectively collected from 3 cancer centers in China. The CT images, as well as the clinical and dosimetric information of patients were retrieved from the medical records. 3 PTV dose related ROIs, including irradiation volume covered by 100%, 105%, and 108% of prescribed dose, combined with 3 skin dose-related ROIs, including irradiation volume covered by 20-Gy, 30-Gy, 40-Gy isodose lines within skin, were contoured for radiomics feature extraction. A total of 4280 radiomics features were extracted from all 6 ROIs. Meanwhile, 29 clinical and dosimetric characteristics were included in the data analysis. A data encapsulation screening algorithm was applied for data cleaning. Multiple-variable logistic regression and 5-fold-cross-validation gradient boosting decision tree (GBDT) were employed for modeling training and validation, which was evaluated by using receiver operating characteristic analysis. Results: The best predictors for symptomatic RD 2+ were the combination of 20 radiomics features, 8 clinical and dosimetric variables, achieving an area under the curve (AUC) of 0.998 [95% CI: 0.996-1.0] and an AUC of 0.911 [95% CI: 0.838-0.983] in the training and validation dataset, respectively, in the 5-fold-cross-validation GBDT model. Meanwhile, the top 12 most important characteristics as well as their corresponding importance measures for RD 2+ prediction in the GBDT machine learning process were identified and calculated. Conclusions: A novel multi-region dose-gradient-based GBDT machine learning framework with a random forest based data encapsulation screening method integrated can achieve a high-accuracy prediction of acute RD 2+ in breast cancer patients.

Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils.

BACKGROUND: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. OBJECTIVES: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. METHODS: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. RESULTS: DEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1ß, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. CONCLUSIONS: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

Capilliposide from Lysimachia capillipes promotes terminal differentiations and reverses paclitaxel resistance in A2780T cells of human ovarian cancer by regulating Fos/Jun pathway.

Objective: To investigate the potential effect of Lysimachia capillipes capilliposide (LCC) on the chemo sensitivity and the stemness of human ovarian cancer cells. Methods: Cell Counting Kit-8 (CCK8) was used to measure the IC50 values. The apoptosis of cells was measured through flow cytometry. Evaluation of the stemness and differentiation markers was performed by the immunoblotting and the immunostaining assays. RNA-seq was performed through the Illumina HiSeq PE150 platform and differentially expressed genes (DEGs) were screened out through the bioinformation analysis. Overexpression or knockdown of Fos gene was achieved by shRNA transfection. Results: Pre-exposure of A2780T cells with 10 µg/mL LCC sensitized them to paclitaxel, of which the IC50 value reduced from 8.644 µmol/L (95%CI: 7.315-10.082 µmol/L) to 2.5 µmol/L (95%CI: 2.233-2.7882 µmol/L). Exposure with LCC enhanced the paclitaxel-induced apoptosis and inhibited the colony formation of A2780T cells. LCC exposure reduced the expression of cancer stemness markers, ALDH1, Myd88 and CD44, while promoting that of terminal differentiation markers, NFATc1, Cathepsin K and MMP9. RNA-seq analysis revealed that the expressions of FOS and JUN were upregulated in LCC-treated A2780T cells. A2780T cells overexpressing Fos gene displayed increased paclitaxel-sensitivity and reduced cell stemness, and shared common phenotypes with LCC-treated A2780T cells. Conclusion: These findings suggested that LCC promoted terminal differentiations of ovarian cancer cells and sensitized them to paclitaxel through activating the Fos/Jun pathway. LCC might become a novel therapy that targets at cancer stem cells and enhances the chemotherapeutic effect of ovarian cancer treatments.

Accelerating Nickel-Based Molecular Construction via DFT Guidance for Advanced Photocatalytic Hydrogen Production.

Understanding the nickel-based molecular catalyst structure and functional relationship is crucial for catalytic hydrogen production in aqueous solutions. Density functional theory (DFT) provides mature theoretical knowledge for efficient catalyst design, significantly reducing catalyst synthesis time and energy consumption. In the present work, three molecular catalysts, Ni(qbz)(pys)2 (qbz = 2-quinoline benzimidazole) (NQP 1), Ni(qbo)(pys)2 (qbo = 2-quinoline benzothiazole) (NQP 2), and Ni(pbz)(pys)2 (pbz = 4-chloro-2,2-pyridylbenzimidazole) (NQP 3) (pys = 2-mercaptopyridine), were designed and synthesized and exhibit a high performance for H2 generation in aqueous solution with a lamp (λ ≥ 400 nm) under visible light irradiation. Under the optimal conditions, a H2 evolution rate as high as 1190 µmol h-1 can be obtained over 25 mg of NQP 1 with the best catalytic performance. DFT has been adopted in this study to unveil the relationship between the ligand qbz and catalyst NQP 1─an efficient step in the design of catalysts with an excellent catalytic performance. We show that, in addition to the presence of the triphenyl ring increasing the overall electron density, rapid electron transfer (ET) from excited fluorescein (Fl) to NQP 1 significantly improves the chance of photogenerated electrons transferring to the active site, ultimately increasing the catalytic activity for H2 production. This work on understanding the correlation between structures and properties of complexes provides a new idea for manufacturing high-performance photocatalysts.

A nanoflower-like polypyrrole-based cobalt-nickel sulfide hybrid heterostructures with electrons migration to boost overall water splitting.

The development of high-efficiency and cost-effective difunctional electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are highly attractive to fulfill the practical water electrolysis. Herein, a novel low-cost difunctional cobalt-nickel sulfide (Co3S4/Ni3S2) flower-like heterostructures are purposely loaded on the surface of polypyrrole (PPy) nanosheets on nickel foam (NF) via feasible and efficient electrodeposition and hydrothermal tactics. The unique hierarchical architecture of the PPy nanosheets and strong electron interaction in the Co3S4/Ni3S2 nanohybrid effectively offer sufficient specific surface area and regulate electronic configuration for expediting the electrocatalytic process. The theoretical simulations also provide convincing proof that the interface of the Co3S4/Ni3S2 heterostructures supplies a lower energy pathway for water adsorption and dissociation, and the electrons migration that occurs when heterostructures emerge is probably the root of the result above. Consequently, the as-fabricated Co3S4/Ni3S2@PPy/NF exhibits outstanding electrochemical activity of HER and OER requiring low overpotentials of 63 mV and 207 mV to reach a current density of 10 mA cm-2 in the alkaline electrolyte, respectively. When equipped in a two-electrode electrolyzer, the Co3S4/Ni3S2@PPy/NF electrode couple displays a low voltage of only 1.52 V at 10 mA cm-2, indicating its potential application in the field of the water electrolysis.

CircATL2 enhances paclitaxel resistance of ovarian cancer via impacting miR-506-3p/NFIB axis.

Circular RNAs (circRNAs) play vital regulatory roles in the development of ovarian cancer (OC). However, the functions of circRNA Atlastin GTPase 2 (circATL2) in paclitaxel (PTX) resistance of OC are still unclear. As a result, circATL2 was upregulated in PTX-resistant OC tissues and cells. CircATL2 knockdown reduced IC50 of PTX, inhibited colony formation ability and promoted cell cycle arrest and apoptosis in PTX-resistant OC cells. Silencing of circATL2 restrained PTX resistance in vivo. Furthermore, miR-506-3p could be targeted by circATL2 and miR-506-3p inhibition reversed the impacts of circATL2 knockdown on PTX resistance and cell progression in PTX-resistant OC cells. NFIB was identified as the target of miR-506-3p. MiR-506-3p overexpression suppressed PTX resistance and malignant behaviors of PTX-resistant OC cells, with NFIB elevation rescued the impacts. To summarize, circATL2 promoted the resistance of OC to PTX by sponging miR-506-3p to upregulate NFIB expression, providing a new sight in chemoresistance of OC.

AZD3759 enhances radiation effects in non-small-cell lung cancer by a synergistic blockade of epidermal growth factor receptor and Janus kinase-1.

AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system. Although the promising antitumor effects of AZD3759 on non-small cell lung cancer (NSCLC) have been demonstrated in clinical trials, the regulatory effects of this inhibitor on the antitumor efficacy of radiation (RA) are unclear. The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759. We found that the survival in RA-treated NSCLC cells was significantly decreased by treatment with 500 nM AZD3759 and osimertinib at the RA dosage of 8 Gy. The apoptotic rate, cell cycle arrest, and DNA damage in RA-treated NSCLC cells and brain metastasis in RA-treated xenograft nude mice were significantly enhanced by the co-administration of AZD3759 and osimertinib, respectively. In addition, AZD3759 showed a significantly stronger efficacy than osimertinib did. Mechanistically, the receptor tyrosine kinase signaling antibody array revealed that Janus kinase-1 (JAK1) was specifically inhibited by AZD3759, but not by osimertinib. The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.