Interleukin-17F suppressed colon cancer by enhancing caspase 4 mediated pyroptosis of endothelial cells.

The combination of anti-angiogenic treatment and immunotherapy presents a promising strategy against colon cancer. Interleukin-17F (IL-17F) emerges as a critical immune cell cytokine expressed in colonic epithelial cells, demonstrating potential in inhibiting angiogenesis. In order to clarify the roles of IL-17F in the colon cancer microenvironment and elucidate its mechanism, we established a mouse colon carcinoma cell line CT26 overexpressing IL-17F and transplanted it subcutaneously into syngeneic BALB/c mice. We also analyzed induced colon tumor in IL-17F knockout and wild type mice. Our results demonstrated that IL-17F could suppress colon tumor growth in vivo with inhibited angiogenesis and enhanced recruitment of cysteine-cysteine motif chemokine receptor 6 (CCR6) positive immune cells. Additionally, IL-17F suppressed the tube formation, cell growth and migration of endothelial cells EOMA in vitro. Comprehensive bioinformatics analysis of transcriptome profiles between EOMA cells and those treated with three different concentrations of IL-17F identified 109 differentially expressed genes. Notably, a potential new target, Caspase 4, showed increased expressions after IL-17F treatment in endothelial cells. Further molecular validation revealed a novel downstream signaling for IL-17F: IL-17F enhanced Caspase 4/GSDMD signaling of endothelial cells, CT26 cells and CT26 transplanted tumors, while IL-17F knockout colon tumors exhibited decreased Caspase 4/GSDMD signaling. The heightened expression of the GSDMD N-terminus, coupled with increased cellular propidium iodide (PI) uptake and lactate dehydrogenase (LDH) release, revealed that IL-17F promoted pyroptosis of endothelial cells. Altogether, IL-17F could modulate the colon tumor microenvironment with inhibited angiogenesis, underscoring its potential as a therapeutic target for colon cancer.

CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice.

Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and ß2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and ß2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

Genome Editing VEGFA Prevents Corneal Neovascularization In Vivo.

Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV-SpCas9/sgRNA-VEGFA system is demonstrated which blocks suture-induced expression of VEGFA, CD31, and α-smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Nonmetal Graphdiyne Nanozyme-Based Ferroptosis-Apoptosis Strategy for Colon Cancer Therapy.

Ferroptosis-apoptosis, a new modality of induced cell death dependent on reactive oxygen species, has drawn tremendous attention in the field of nanomedicine. A metal-free ferroptosis-apoptosis inducer was reported based on boron and nitrogen codoped graphdiyne (BN-GDY) that possesses efficient glutathione (GSH) depletion capability and concurrently induces ferroptosis by deactivation of GSH-dependent peroxidases 4 (GPX4) and apoptosis by downregulation of Bcl2. The high catalytic activity of BN-GDY is explicated by both kinetic experiments and density functional theory (DFT) calculations of Gibbs free energy change during hydrogen peroxide (H2O2) decomposition. In addition, a unique sequence Bi-Bi mechanism is discovered, which is distinct from the commonly reported ping-pong Bi-Bi mechanism of most peroxidase mimics and natural enzymes. We anticipate that this nonmetal ferroptosis-apoptosis therapeutic concept by carbon-based nanomaterials would provide proof-of-concept evidence for nanocatalytic medicines in cancer therapy.

Porous FeO x /carbon nanocomposites with different iron oxidation degree for building high-performance lithium ion batteries.

Transition metal oxides have attracted lots of interest for lithium ion battery (LIB) due to the high theoretical capacity, however, the large specific volume change, low electrical conductivity and slow intrinsic lithiation/delithiation still limit the practical applications. In order to overcome the challenge, a novel type of high temperature annealing treatment for the synthesis of 3D porous FeO x nanocrystals embedded in a partially carbon matrix as an example for high-performance LIB is reported. The FeO x /carbon nanocomposites with coral-like architecture achieved at 700 °C (F700) exhibit good long term cyclability with a reversible capacity 1012 mAh g-1 remain after 500 cycles at 1.0 A g-1 and the high rate capacity with a reversible capacity of 233 mAh g-1 even at extremely high current density of 20 A g-1. These excellent electrochemical performances could be attributed to the 3D porous structure and carbon coating, which could not only provide excellent electronic conductivity and enough elastic buffer space to accommodate volume changes upon lithium insertion/extraction, but also effectively avoid agglomeration of the Fe3O4 nanocrystals and maintain the structural integrity of the electrode during the charge/discharge process.

Hierarchical self-assembly flower-like ammonium nickel phosphate as high-rate performance electrode material for asymmetric supercapacitors with enhanced energy density.

Ammonium nickel phosphate has a large specific capacitance as an electrode material at low current density, but its capacitance decays fast at high current density, which directly affects the rate performance of supercapacitors. Herein, we demonstrate a facile route for the controllable synthesis of hierarchical self-assembly flower-like ammonium nickel phosphate as a high-rate electrode material for asymmetric supercapacitors, which is an important strategy to enhance the energy density at high power density. The flower-like structures are hierarchically assembled by a mass of rectangular sheets, which can provide fast electron transport and short ion diffusion path, thereby exhibiting excellent electrochemical performance with ultrahigh specific capacitance of 1016 F g-1 at 1.0 A g-1. More importantly, the NH4NiPO4 · H2O materials exhibit outstanding rate performance (800 F g-1 even at large current density of 30 A g-1) and superior long-term cycle life (83% of capacity retention up to 3000 cycles at 5 A g-1). Furthermore, the NH4NiPO4 · H2O//AC asymmetric supercapacitors are assembled in aqueous KOH electrolyte, and exhibit high energy density (46.2 Wh kg-1 at 160 W kg-1 and 26.7 Wh kg-1 at a large power density of 4000 W kg-1, respectively). Due to the outstanding electrochemical performance, the all-solid-state asymmetric supercapacitors are successfully constructed using these materials.

Extended nursing for the recovery of urinary functions and quality of life after robot-assisted laparoscopic radical prostatectomy: a randomized controlled trial.

PURPOSE: The purpose of this work is to explore the effects of continuing nursing care intervention on postoperative urinary control and quality of life among patients with prostate cancer. METHODS: This was a single-center, parallel, and randomized controlled trial that was carried out at the Department of Urology, the First Affiliated Hospital of Anhui Medical University, China. The participants underwent robot-assisted laparoscopic radical prostatectomy (RARP) between October 2014 and April 2016. The patients were randomized to the experimental and control groups (n=37/group). Patients in the control group received routine nursing care, while patients in the experimental group received continuing nursing care. During the 6-month follow-up, each patient was invited at the hospital discharge and at 1, 3, and 6 months to fill the ICI-Q-SF and SF-36 questionnaires. RESULTS: The scores of urinary incontinence were improved in the intervention group compared with controls at 3 and 6 months after discharge (both P < 0.01). The scores of quality of life in the experimental group were significantly higher than control group at 1, 3, and 6 months (all P < 0.01). Adverse events were mild or moderate in intensity and were resolved in all patients. All adverse events were related to RARP. CONCLUSIONS: Continuing nursing care intervention had significant beneficial effects on urinary functions and quality of life in patients with prostate cancer after RARP. This approach warrants to be promoted in the clinical setting.

Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release.

We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95-5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics.

Copper-Catalyzed Click Reaction on/in Live Cells.

We demonstrated that copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction could be performed inside live mammalian cells without using a chelating azide. Under optimized conditions, the reaction was performed in human ovary cancer cell line OVCAR5 in which newly synthesized proteins were metabolically modified with homopropargylglycine (HPG). This model system allowed us to estimate the efficiency of the reaction on the cell membranes and in the cytosol using mass spectrometry. We found that the reaction was greatly promoted by a tris(triazolylmethyl)amine CuI ligand tethering a cell-penetrating peptide. Uptake of the ligand, copper, and a biotin-tagged azide in the cells was determined to be 69 ± 2, 163 ± 3 and 1.3 ± 0.1 µM, respectively. After 10 minutes of reaction, the product yields on the membrane and cytosolic proteins were higher than 18% and 0.8%, respectively, while 75% cells remained viable. By reducing the biothiols in the system by scraping or treatment with N-ethylmalemide, the reaction yield on the cytosolic proteins was greatly improved to ~9% and ~14%, respectively, while the yield on the membrane proteins remained unchanged. The results indicate that out of many possibilities, deactivation of the current copper catalysts by biothiols is the major reason for the low yield of CuAAC reaction in the cytosol. Overall, we have improved the efficiency for CuAAC reaction on live cells by 3-fold. Despite the low yielding inside live cells, the products that strongly bind to the intracellular targets can be detected by mass spectrometry. Hence, the in situ CuAAC reaction can be potentially used for screening of cell-specific enzyme inhibitors or biomarkers containing 1,4-substituted 1,2,3-triazoles.

Suicidal ideation among Chinese cancer inpatients of general hospitals: prevalence and correlates.

Cancer patients are at high risk for suicide, particularly when they are informed about the cancer diagnosis or hospitalized for cancer treatment. Therefore, oncology healthcare settings such as large general hospitals in China, may represent an ideal setting to identify and treat suicidality in cancer patients. However, the clinical epidemiology of suicidality of Chinese cancer patients remains largely unknown. This study examined the prevalence and correlates of suicidal ideation among Chinese cancer inpatients of large general hospitals. A total of 517 cancer inpatients were consecutively recruited from two tertiary general hospitals of a metropolitan city in northern China, and administered with standardized questionnaires to collect data on sociodemographics, mental health, and cancer-related clinical characteristics. Suicidal ideation and mental health were measured with a single self-report question "In the past month, did you think about ending your life?" and Hospital Anxiety and Depression Scale, respectively. The one-month prevalence of suicidal ideation was 15.3% in Chinese cancer inpatients. In multivariable Logistic regression, depression, anxiety, moderate-to-severe pain, metastatic cancer, poor performance status, surgery, and palliative care were significantly associated with suicidal ideation. Cancer inpatients of large Chinese general hospitals have high prevalence of suicidal ideation and therefore potentially at high risk for suicide. Suicide prevention efforts for cancer inpatients should include periodic evaluation of suicidality, effective pain management, psychooncological supports, and, when necessary, psychiatric treatment and crisis intervention.

Extent of the Oxidative Side Reactions to Peptides and Proteins During the CuAAC Reaction.

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful tool for bioconjugation of biomolecules, particularly proteins and peptides. The major drawback limiting the use of the CuAAC reaction in biological systems is the copper-mediated formation of reactive oxygen species (ROS), leading to the oxidative degradation of proteins or peptides. From the studies on a limited number of proteins and peptides, it is known that, in general, the copper mediated oxidative damage is associated with the copper coordination environment and solvent accessibility. However, there is a lack of data to help estimate the extent of copper-mediated oxidation on a wide range of proteins and peptides. To begin to address this need, we quantitatively measured the degree of copper-mediated oxidation on libraries of 1200 tetrapeptides and a model protein (bovine serum albumin, BSA) using liquid chromatography mass spectrometry (LC-MS). The collected data will be useful to researchers planning to use the CuAAC reaction for bioconjugaton on peptides or proteins.

Modification of fluorous substrates with oligo(ethylene glycol) via "click" chemistry for long-term resistance of cell adhesion.

In this work perfluorinated substrates fabricated from SiO2 glass slides are modified with oligo(ethylene glycol) (OEG) units for long-term resistance of cell adhesion purposes, based on fluorous interactions and click chemistry. Specifically, fluorous substrates, prepared by treatment of glass slides with 1H, 1H, 2H, 2H-perfluorodecyltrimethoxysilane (FAS17), were coated with ethynyl-OEG-C8F17, followed by covalent attachment of an azido-OEG via copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. We demonstrate that the resultant surface avoid fibrinogen adsorption and resisted cell adhesion for over 14days. X-ray photoemission spectroscopy (XPS) analysis and contact angle goniometry measurements confirm the presence of the OEG molecules on the fluorous substrates. Bright field optical images show total absence of 3T3 fibroblast cells on the OEG modified fluorinated substrate for 1 and 5days, and a remarkably decrease of cell adhesion at 14days.

"Click" immobilization of a VEGF-mimetic peptide on decellularized endothelial extracellular matrix to enhance angiogenesis.

We show that coating of decellularized extracellular matrix (DC-ECM) on substrate surfaces is an efficient way to generate a platform mimicking the native ECM environment. Moreover, the DC-ECM can be modified with a peptide (QK) mimicking vascular endothelial growth factor without apparently compromising its integrity. The modification was achieved through metabolic incorporation of a "clickable" handle to DC-ECM followed by rapid attachment of the QK peptide with an azido tag using copper-catalyzed click reaction. The attachment of the QK peptide on to DC-ECM in this way further enhanced the angiogenic responses (formation of branched tubular networks) of endothelial cells.

pH-responsive controlled release of antitumour-active polyoxometalate from mesoporous silica materials.

Two efficient pH-responsive oral delivery systems have been fabricated through a dative bonding between the amino-functionalized mesoporous silica materials, including MCM-41-type mesoporous silica nanospheres (MMSNs) and bimodal mesoporous silica microspheres (BMSMs), and an antitumour-active polyoxometalate K(8)H(2)[Ti(H(2)O)](3)SiW(9)O(34) (Ti(3)SiW(9)). The Ti(3)SiW(9) loaded in the pores of MMSNs and BMSMs are up to 23.72 wt% and 28.69 wt% at pH 6.5, respectively. Both delivery systems reveal an increase of Ti(3)SiW(9) release under mildly alkaline conditions, while zero premature release is observed under acidic and neutral conditions, making them ideal for use as a new class of colon-specific oral delivery systems. Importantly, these systems provide very promising possibilities for many medical applications that require an increase or decrease in the rate of drug release, depending on disease evolution. Upon incorporation into mesoporous silica materials, the antitumour activity of Ti(3)SiW(9) against Ls-174-T was improved from 0.8 mg mL(-1) to 0.186 and 0.102 mg mL(-1) for Ti(3)SiW(9)@MMSN-NH(2) and Ti(3)SiW(9)@BMSM-NH(2), respectively.