Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells

High-grade serous carcinoma (HGSC) is the most common and lethal histotype of ovarian cancer. Radiation is usually used as a second-line treatment against the disease. In spite of numerous clinical studies indicating efficacy of radiation therapy in patients suffering from disease recurrence, it is seldom used clinically due to severe dose-related toxicity. Discovery and utilization of novel radiosensitizers could control the toxicity and enable effective therapeutic application of radiation. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors. Our previous publications showed that CX3CR1 is not expressed in normal ovarian surface epithelium and is expressed in primary and metastatic epithelial ovarian carcinoma. Moreover, transient downregulation of CX3CR1 in ovarian cancer cells will impair their proliferation as well as their migration and adhesion to peritoneal mesothelial cells. Therefore, we proposed combining CX3CR1 downregulation and radiation as a strategy for reducing the dose of radiation while maintaining the therapeutic efficacy. The experimental observations indicated that transient downregulation of CX3CR1 in most HGSC cell lines can lead to radiosensitization, as determined by clonogenic assay. However, loss of CX3CR1 does not affect radiosensitivity in ovarian cancer cells that express wild-type p53. There are several altered characteristics that may contribute to resistance to ionizing radiation, including enhanced DNA damage repair, and adaptive response to the radiation-induced ROS (Reactive Oxygen Species). Specifically, my results indicated that downregulation of CX3CR1 can abrogate the phosphorylation and activation of DNA double-strand break repair related proteins following ionizing radiation. The unrepaired DNA damage leads to damage persistence and ultimately contributes to radiosensitization. Another mechanism by which CX3CR1 knockdown alters radiosensitivity is the regulation of cellular redox capacity, where loss of CX3CR1 leads to elevated ROS levels. Taken together, my study demonstrated for the novel findings that loss of CX3CR1 can sensitize HGSC cells to ionizing radiation through the regulation of DNA damage response and intracellular redox status

Table_1_Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study.pdf

PurposeThis study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors.DesignTwo-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.MethodOur study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included.ResultIn the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30–1.54; P ConclusionOur findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.</p

DataSheet1_Low temperature ensures FeS2 cathode a superior cycling stability in Li7P3S11-based all-solid-state lithium batteries.docx

All-solid-state lithium sulfide batteries exhibit great potential as next-generation energy storage devices due to their low cost and high energy density. However, the poor conductivity of the solid electrolytes and the low electronic conductivity of sulfur limit their development. In this work, the highly conductive Li7P3S11 glass-ceramic solid electrolyte with room temperature conductivity of 1.27 mS cm−1 is synthesized and combined with the FeS2 cathode and Li-In anode to fabricate FeS2/Li7P3S11/Li-In all-solid-state Li-S battery. The assembled battery delivers high initial discharge capacities of 620.8, 866.4 mAh g−1, and 364.8 mAh g−1 at 0.1C under room temperature, 60°C and 0°C, respectively. It shows a discharge capacity of 284.8 mAh g−1 with a capacity retention of 52.4% after 80 cycles at room temperature. When the operating temperature rises to 60°C, this battery suffers a fast decay of capacity in 40 cycles. However, this battery sustains a high discharge capacity of 256.6 mAh g−1 with a capacity retention of 87.9% after 100 cycles under 0°C, smaller volume expansion of ASSBs at 0°C keep the solid/solid contact between the electrolyte particles, thus resulting in better electrochemical performances. EIS and in situ pressure characterizations further verify that the differences of electrochemical performances are associated with the volume variations caused by the temperature effects. This work provides a guideline for designing all-solid-state Li-S which is workable in a wide temperature range.</p

Free-Standing Mn₃O₄@CNF/S Paper Cathodes with High Sulfur Loading for Lithium–Sulfur Batteries

Free-standing paper cathodes with layer-by-layer structure are synthesized for high-loading lithium–sulfur (Li–S) battery. Sulfur is loaded in a three-dimensional (3D) interconnected nitrogen-doped carbon nanofiber (CNF) framework impregnated with Mn₃O₄ nanoparticles. The 3D interconnected CNF framework creates an architecture with outstanding mechanical properties. Synergetic effects generated from physical and chemical entrapment could effectively suppress the dissolution and diffusion of the polysulfides. Electrochemical measurements suggest that the rationally designed structure endows the electrode with high utilization of sulfur and good cycle performance. Specifically, the cathode with a high areal sulfur loading of 11 mg cm^–2 exhibits a reversible areal capacity over 8 mAh cm^–2. The fabrication procedure is of low cost and readily scalable. We believe that this work will provide a promising choice for potential practical applications

Customized Electrolyte and Host Structures Enabling High-Energy-Density Anode-Free Potassium–Metal Batteries

Potassium shows great potential to replace lithium in energy storage for its high abundance and comparable energy density. However, issues including an unstable interphase, dendrite growth, and volume change restrict the development of potassium metal batteries, and so far, there is no single cure that works once and for all. Here an anode-free potassium metal battery is demonstrated by introducing a customized electrolyte and host structures that simultaneously promote efficiency, reversibility, and energy density. First, a diluted high-concentration electrolyte with fast kinetics and high stability triggers an inorganic-rich durable interphase. Meanwhile, a carbonaceous host containing narrowly distributed mesopores (MCNF) favors reduced surface area but enough inner space. Together, they achieve a high average Coulombic efficiency (CE) of 99.3% and an initial CE of 95.9% at 3 mA cm–2–3 mA h cm–2. Anode-free MCNF||Prussian blue (PB) potassium cells are delivered with 100 reversible cycles and a high energy density of 362 W h kg–1