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.

Advancing botanical safety: A strategy for selecting, sourcing, and characterizing botanicals for developing toxicological tools.

Increases in botanical use, encompassing herbal medicines and dietary supplements, have underlined a critical need for an advancement in safety assessment methodologies. However, botanicals present unique challenges for safety assessment due to their complex and variable composition arising from diverse growing conditions, processing methods, and plant varieties. Historically, botanicals have been largely evaluated based on their history of use information, based primarily on traditional use or dietary history. However, this presumption lacks comprehensive toxicological evaluation, demanding innovative and consistent assessment strategies. To address these challenges, the Botanical Safety Consortium (BSC) was formed as an international, cross-sector forum of experts to identify fit-for purpose assays that can be used to evaluate botanical safety. This global effort aims to assess botanical safety assessment methodologies, merging traditional knowledge with modern in vitro and in silico assays. The ultimate goal is to champion the development of toxicity tools for botanicals. This manuscript highlights: 1) BSC's strategy for botanical selection, sourcing, and preparation of extracts to be used in in vitro assays, and 2) the approach utilized to characterize botanical extracts, using green tea and Asian ginseng as examples, to build confidence for use in biological assays.

A new sesquiterpene from endophytic fungus Colletotrichum sp. B-89.

A new sesquiterpene, named (1S, 4aS, 7 R, 8 R, 8aR) Decahydro-1,4a-dimethyl-7-(1-methylethyl)-1,8-naphthalenediol (1), and six known compounds (2-7) were obtained from Colletotrichum sp. B-89, an endophytic fungus isolated from Dracaena cochinchinensis collected at Xishuangbanna, Yunnan. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data, and the structure of 1 was further determined by X-ray diffraction analysis. The antibacterial activities of above compounds were assayed and compound 6 exhibited certain activities against S. aureus ATCC 25923, B. subtilis ATCC 6633, E. coli ATCC 25922, and K. pneumoniae ATCC 13883.

Two new diketopiperazines from the Cordyceps fungus Samsoniella sp. XY4.

Two new diketopiperazines, namely samsoniellain A (1) and samsoniellain B (2), together with two known compounds (3, 4) were isolated from Cordyceps fungus Samsoniella sp. XY4. The planar structures of 1 and 2 were determined by HRESIMS, 1D and 2D NMR spectroscopy. The absolute configurations of 1 and 2 were determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Results of antimicrobial activity indicated that compound 2 showed weak bacteriostatic activities against S. typhimurium χ 8956, H. influenza ATCC 10211, MRSA 2024 with the MIC values of 128, 256, and 256 µg ml-1, respectively. This is the first report about secondary metabolites of Samsoniella sp.

Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease.

Uveitis is a complex ocular inflammatory disease with a multifactorial etiology that can result in blindness. Although corticosteroid eye drops are the primary treatment for anterior uveitis, their efficacy is limited by low bioavailability, adverse effects, and a narrow focus on inflammation. In this study, the multifunctional hydrogel eye drops (designated as DCFH) were developed by incorporating the anti-inflammatory agent dexamethasone (DSP) and reactive oxygen species (ROS) scavenger cerium-based metal-organic frameworks (Ce-MOFs) into thermosensitive triblock copolymer F127 for the synergistic treatment against uveitis. The resulting F127 eye drops offer a favorable alternative to ophthalmic solution due to its thermosensitivity, thixotropy, light transmittance, improved ocular bioavailability, and unexpected anti-inflammatory efficacy. Notably, the participation of nanoporous Ce-MOFs, functional drug carriers, not only reduces ROS level but also boosts the anti-inflammatory activity of DSP in vitro. Therapeutically, the multifunctional DCFH exhibits superior efficacy in treating endotoxin-induced uveitis by mitigating the ophthalmic inflammatory reaction, suppressing inflammatory cytokines (e.g., TNF-α, IL-6, and IL-17) and downregulating the expression of iNOS and NLPR3. This synergistic treatment provides a valuable and promising approach for the management of uveitis and other ocular inflammatory conditions.

Complexation of Sulfonate-Containing Polyurethane and Polyacrylic Acid Enables Fabrication of Self-Healing Hydrogel Membranes with High Mechanical Strength and Excellent Elasticity.

Artificial hydrogel membranes with good biocompatibility are strongly needed in biological fields. The preparation of biocompatible hydrogel membranes simultaneously possessing high mechanical strength, excellent elasticity, and satisfactory self-healing properties remains a challenge. Herein, we demonstrate the preparation of such hydrogel membranes by complexation of sulfonate-containing polyurethane (SPU) and poly(acrylic acid) (PAA) in the presence of Zn2+ ions followed by swelling in water (denoted as SPU-PAA/Zn). Originating from the synergy of the coordination and hydrogen-bonding interactions and the reinforcement effect of the in situ formed hydrophobic domains, the SPU-PAA/Zn hydrogel membrane exhibits a high tensile strength of ∼7.1 MPa and a toughness of ∼30.4 MJ m-3. Moreover, the hydrogel membrane is highly elastic, which can restore to its initial state from an ∼500% strain within 40 min rest at room temperature without any external assistance. The dynamic noncovalent interactions and hydrophobic domains allow the fractured hydrogel membrane to heal and completely regain its original integrity and mechanical properties at room temperature. Both in vitro and in vivo tests confirm that the hydrogel membrane exhibits satisfactory biocompatibility and could be potentially used as a biological barrier membrane in surgical operations or artificial organs.

Assessment of corneal biomechanics in anisometropia using Scheimpflug technology.

Purpose: To investigate the relationship between corneal biomechanical and ocular biometric parameters, and to explore biomechanical asymmetry between anisometropic eyes using the corneal visualization Scheimpflug technology device (Corvis ST). Methods: 180 anisometropic participants were included. Participants were divided into low (1.00≤△Spherical equivalent (SE) < 2.00D), moderate (2.00D≤△SE < 3.00D) and high (△SE ≥ 3.00D) anisometropic groups. Axial length (AL), keratometry, anterior chamber depth (ACD) and corneal biomechanical parameters were assessed using the OA-2000 biometer, Pentacam HR and Corvis ST, respectively. Results: The mean age of participants was 16.09 ± 5.64 years. Stress-Strain Index (SSI) was positively correlated with SE (r = 0.501, p < 0.001) and negatively correlated with AL (r = -0.436, p < 0.001). Some other Corvis ST parameters had weak correlation with SE or AL. Corneal biomechanical parameters except for time of first applanation (A1T), length of second applanation (A2L), deformation amplitude (DA), first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) were correlated with ametropic parameters (SE or AL) in multiple regression analyses. A1T, velocity of first applanation (A1V), time of second applanation (A2T), A2L, velocity of second applanation (A2V), corneal curvature radius at highest concavity (HCR), peak distance (PD), DA, deformation amplitude ratio max (2 mm) (DAR), SPA1, integrated radius (IR), and SSI showed significant differences between fellow eyes (p < 0.05). There was no significant difference in asymmetry of corneal biomechanics among the three groups (p > 0.05). Asymmetry of some biomechanical parameters had weak correlation with asymmetry of mean corneal curvatures and ACD. However, asymmetry of corneal biomechanical parameters was not correlated with asymmetry of SE or AL (p > 0.05). Conclusion: More myopic eyes had weaker biomechanical properties than the contralateral eye in anisometropia. However, a certain linear relationship between anisometropia and biomechanical asymmetry was not found.

Development and Validation of a Self-Administered Screening Test for Betel Quid Use Disorders in Betel Quid Chewers in Hunan, China.

Introduction: Processed betel quid product chewing is a public health problem in areca non-plant areas in China. However, there is no valid instrument to screen for betel quid use disorder (BQUD) in mainland China. We developed a self-administered screening test for betel quid use disorders (SST-BQUD) and tested its reliability and validity in a sample of betel quid chewers (BQCers) in Hunan, China. Methods: Items of SST-BQUD were selected from the test results of an item pool, which includes 52 questions related to the psycho-social and behavioral presentations of BQUD. All participants, in a self-administered manner, completed the item pool. A subsample completed the re-test one week later. Two psychiatrists interviewed all participants to ascertain the presence of BQUD. The receiver Operating Characteristic curve was used to determine the best cut-off value to discriminate BQUD. Results: One hundred and twelve BQCers were recruited. Based on the statistical analysis of receiver operating characteristic (ROC) curves, 14 yes/no questions were selected for SST-BQUD. As indicated by Cronbach's α coefficient, the internal consistency was 0.876. The area under the curve of SST-BQUD was 0.881, representing a satisfactory diagnostic value. The one-week re-test reliability test was 0.771 (P<0.001), suggesting good stability over time. The optimal cut-off score for BQUD screening was six, with a sensitivity of 0.921 and a specificity of 0.716, implying the satisfactory accuracy of SST-BQUD to screen for BQUD. Conclusion: The standard version of SST-BQUD consists of 14 items. The total score of SST-BQUD was the sum of affirmative answers, with higher scores denoting a more severe BQUD symptom. If one answered six or more times "yes" to these 14 questions, they can be classified with BQUD. The SST-BQUD is a valid screening method for BQUD among BQCers in betel quid processed area.

Engineering Oxygen Vacancies on Mixed-Valent Mesoporous α-MnO2 for High-Performance Asymmetric Supercapacitors.

Intrinsically poor conductivity and sluggish ion-transfer kinetics limit the further development of electrochemical storage of mesoporous manganese dioxide. In order to overcome the challenge, defect engineering is an effective way to improve electrochemical capability by regulating electronic configuration at the atomic level of manganese dioxide. Herein, we demonstrate effective construction of defects on mesoporous α-MnO2 through simply controlling the degree of redox reaction process, which could obtain a balance between Mn3+/Mn4+ ratio and oxygen vacancy concentration for efficient supercapacitors. The different structures of α-MnO2 including the morphology, specific surface area, and composition are successfully constructed by tuning the mole ratio of KMnO4 to Na2SO3. The electrode materials of α-MnO2-0.25 with an appropriate Mn3+/Mn4+ ratio and abundant oxygen vacancy showed an outstanding specific capacitance of 324 F g-1 at 0.5 A g-1, beyond most reported MnO2-based materials. The asymmetric supercapacitors formed from α-MnO2-0.25 and activated carbon can present an energy density as high as of 36.33 W h kg-1 at 200 W kg-1 and also exhibited good cycle stability over a wide voltage range from 0 to 2.0 voltage (kept at approximately 98% after 10 000 cycles in galvanostatic cycling tests) and nearly 100% Coulombic efficiency. Our strategy lays a foundation for fine regulation of defects to improve charge-transfer kinetics.

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.

High Energy Density in Combination with High Cycling Stability in Hybrid Supercapacitors.

Hybrid supercapacitors are considered the next-generation energy storage equipment due to their superior performance. In hybrid supercapacitors, battery electrodes need to have large absolute capacities while displaying high cycling stability. However, enhancing areal capacity via decreasing the size of electrode materials results in reductions in cycling stability. To balance the capacity-stability trade-off, rationally designed proper electrode structures are in urgent need and still of great challenge. Here we report a high-capacity and high cycling stability electrode material by developing a nickel phosphate lamination structure with ultrathin nanosheets as building blocks. The nickel phosphate lamination electrode material exhibits a large specific capacity of 473.9 C g-1 (131.6 mAh g-1, 1053 F g-1) at 2.0 A g-1 and only about 21% capacity loss at 15 A g-1 (375 C g-1, 104.2 mAh g-1, 833.3 F g-1) in 6.0 M KOH. Furthermore, hybrid supercapacitors are constructed with nickel phosphate lamination and activated carbon (AC), possessing high energy density (42.1 Wh kg-1 at 160 W kg-1) as well as long cycle life (almost 100% capacity retention after 1000 cycles and 94% retention after 8000 cycles). The electrochemical performance of the nickel phosphate lamination structure not only is commensurate with the nanostructure or ultrathin materials carefully designed in supercapacitors but also has a longer cycling lifespan than them. The encouraging results show the great potential of this material for energy storage device applications.

Silver Peroxide Nanoparticles for Combined Antibacterial Sonodynamic and Photothermal Therapy.

Metal peroxide nanoparticles designed to elevate the oxidative stress are considered a promising nanotherapeutics in biomedical applications, including chemotherapy, photodynamic therapy, and bacterial disinfection. However, their lack of specificity towards the therapeutic target can cause toxic side effects to healthy tissues. Here, silver peroxide nanoparticles (Ag2 O2 NPs) capable of controlled reactive oxygen species (ROS) release are synthesized. The release of bactericidal Ag+ ions and ROS is strictly regulated by external stimuli of ultrasound (US) and near-infrared (NIR) light. In vitro and in vivo investigations show that the Ag2 O2 NPs present enhanced antibacterial and antibiofilm capabilities with a killing efficiency >99.9999% in 10 min, significantly accelerate multi-drug resistant Staphylococcus aureus infected skin wound closure with excellent cytocompatibility and hemocompatibility. This work not only provides the first paradigm for fabricating silver peroxide nanoparticle but also introduces a highly efficient noninvasive and safe therapeutic modality for combating bacterial infectious diseases.

Research on the Impact of Regional Economy on Industrial Development from the Perspective of Big Data.

In order to study the driving force of China's rapid economic development in the past ten years, the study takes Guizhou, Yunnan, and Guangxi as a case study, focusing on the big data assets exchange (GBDEx) and Beibu Gulf Economic Zone, and discusses the impact of Internet plus economic and government data and the big data system on regional economy. Finally, it is believed that the Internet and big data fully avoid the disadvantages of traffic distance between the western region and the eastern region, make full and efficient cooperation between enterprises and institutions in the central and western regions and Chinese and foreign economic entities, and strengthen the control of economic behavior from the big data level with the support of the service-oriented government. The information entropy output from the Internet big data system has led to a significant entropy reduction process in China's economic environment and a more orderly economic system, which is also an important reason for the rapid development of China's economy.

Pomegranate-Like CuO2@SiO2 Nanospheres as H2O2 Self-Supplying and Robust Oxygen Generators for Enhanced Antibacterial Activity.

Reactive oxygen species (ROS)-induced nanosystems represent one of the most essential, efficient, and encouraging nanobactericides for eliminating bacterial infection concerning the increasing resistance threats of existing antibiotics. Among them, Fenton-type metal peroxide nanoparticles are exciting nanomaterials with intriguing physiochemical properties, yet the study of this antimicrobial agent is still in its infancy. Herein, a robust pH-responsive Fenton nanosystem is constructed by the assembly of copper peroxide nanodots in pomegranate-like mesoporous silica nanoshells (CuO2@SiO2) that are capable of self-supplying H2O2 and sustainably generating O2. The enhanced antimicrobial performance is attributed to the pH responsiveness and excellent Fenton catalytic activity through either the Cu2+-catalyzed conversion of H2O2 to detrimental ROS under acid treatment or in situ O2 evolution in neutral media. Moreover, in vitro and in vivo investigations demonstrate that this nanocomposite can exhibit boosted antimicrobial capabilities and can significantly accelerate skin wound closure, while retaining outstanding cytocompatibility and hemocompatibility. Given its excellent physicochemical and antimicrobial properties, the broad application of this nanocomposite in bacteria-associated wound management is anticipated.

Seeded 2D epitaxy of large-area single-crystal films of the van der Waals semiconductor 2H MoTe2.

The integration of two-dimensional (2D) van der Waals semiconductors into silicon electronics technology will require the production of large-scale, uniform, and highly crystalline films. We report a route for synthesizing wafer-scale single-crystalline 2H molybdenum ditelluride (MoTe2) semiconductors on an amorphous insulating substrate. In-plane 2D-epitaxy growth by tellurizing was triggered from a deliberately implanted single seed crystal. The resulting single-crystalline film completely covered a 2.5-centimeter wafer with excellent uniformity. The 2H MoTe2 2D single-crystalline film can use itself as a template for further rapid epitaxy in a vertical manner. Transistor arrays fabricated with the as-prepared 2H MoTe2 single crystals exhibited high electrical performance, with excellent uniformity and 100% device yield.

Degradable Poly(vinyl alcohol)-Based Supramolecular Plastics with High Mechanical Strength in a Watery Environment.

It is challenging to fabricate degradable poly(vinyl alcohol) (PVA)-based plastics that can be used in watery environments because PVA is soluble in water. In this study, PVA-based supramolecular plastics with excellent degradability in soil and high mechanical strength in watery environments are fabricated by the complexation of vanillin-grafted PVA (VPVA), hydrophobic humic acid (HA), and Fe3+ ions (hereafter denoted as VPVA-HA-Fe complexes). Large-area PVA-based plastics can be easily prepared from a solution of VPVA-HA-Fe complexes using a blade-coating method. The high-density of hydrogen bonds and coordination interactions, as well as the reinforcement of self-assembled Fe3+ -chelated HA nanoparticles, facilitate the fabrication of PVA-based plastics with a breaking strength of ≈85.0 MPa. After immersion in water at room temperature for 7 d, the PVA-based plastics exhibit a breaking strength of ≈26.2 MPa, which is similar to that of polyethylene in its dry state. Furthermore, owing to the reversibility of the hydrogen bonds and coordination interactions, the VPVA-HA-Fe plastics are recyclable and can be conveniently processed into plastic products with desired shapes. After being placed under soil for ≈108 d, the PVA-based plastics are completely degraded into nontoxic species without requiring manual interference.

Self-assembled nanogels of luminescent thiolated silver nanoclusters and chitosan as bactericidal agent and bacterial sensor.

Multifunctional theranostic agents with the features of good biocompatibility, long-term antibacterial efficacy, and rapid bacterial detection are the desired future medicine for infectious diseases, but which poses huge challenges on the design of such multifunctional nanocomposites in a single entity. Herein, self-assembled nanogels of thiolated silver nanoclusters (Ag NCs) and chitosan was designed and synthesized, which combines the desirable biocompatible, targeting specific, luminescent properties. This nanogel displays an amplified luminescence via strong matrix-ligand coordination between thiolate ligands and chitosan matrix to rigidify the molecular structure on the surface of Ag NCs. Concomitantly, this nanogel exhibits exceptional bactericidal activity, with approximately >10-fold stronger activity compared to its counterpart Ag NCs. Furthermore, a bacterial detection system was developed based on the bacterial binding on the fluorescent nanogels. This work provides a new strategy in designing multifunctional theranostic agents and this new composite Ag NC nanogel holds great promise for practical applications as the theranostic nanomedicines.

Polymeric Complex-Based Transparent and Healable Ionogels with High Mechanical Strength and Ionic Conductivity as Reliable Strain Sensors.

Transparent and healable ionogels with very high mechanical strength, ionic conductivity, and resilience were fabricated for use as strain sensors with satisfactory reliability. The ionogels were fabricated by casting an aqueous solution of poly(vinyl alcohol) (PVA)-poly(vinylpyrrolidone) (PVP) complexes and 1-ethyl-3-methylimidazolium dicyanamide ([EMIm][DCA]), followed by evaporation of water at room temperature. The use of [EMIm][DCA] endowed the resulting ionogels with ionic conductivity at room temperature as high as 19.7 mS cm-1. Owing to the synergy between the abundant number of hydrogen bonds between PVA and PVP and the crystallized PVA segments that served as nanofillers, the resulting ionogels had good mechanical properties with a tensile stress of 7.7 MPa, a strain of 821%, and good resilience. In addition, the resulting ionogels showed rapid and repeatable sensing signals over a wide strain range (0.1-400%). This enabled them to detect both vigorous muscle movements, such as walking and jumping, and subtle muscle movements, such as pulse. Moreover, owing to the reversibility of hydrogen bonds, physically damaged mechanical properties, conductivity, and sensing ability of the ionogels could be conveniently healed with the assistance of water.