Multicomponent reaction synthesis and evaluation of novel 3,4-dihydropyrazine[1,2-b]Indazole-1(2H)-one derivatives as inhibitors of pyroptosis and inflammation.

Inflammation is a protective response by the body aimed at maintaining tissue homeostasis by eliminating pathogenic microbial infection, irritants, or tissue damage. However, dysregulated inflammation is pathological and involved in various diseases such as metabolic disorders, cancer, and neurodegenerative diseases. In this study, multicomponent reaction, an efficient tool for the synthesis of complex compounds with potential biological activities, was employed to synthesize twenty 3,4-dihydro-pyrazine[1,2-b]indazole-1(2H)-one derivatives and two 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one analogues.

Thiophene Expanded Self-Assembled Monolayer as Hole Transport Layer for Organic Solar Cells with Efficiency of 20.78.

Carbazole-derived self-assembled monolayers (SAMs) as hole transport layers (HTLs) have achieved groundbreaking progress of device efficiency in perovskite and organic photovoltaics. Expanding the π-conjugation of carbazole is an effective approach to enhance the molecular dipole moment and facilitate charge extraction of SAMs. However, this strategy tends to cause poor solubility and excessive self-aggregation of SAMs.

NO-generating self-delivery liposomes for synergistic photodynamic-gas therapy against hypoxic tumors.

Photodynamic therapy (PDT) is an effective non-invasive tumor treatment strategy that has been widely used for anti-tumor therapy. However, the hypoxic tumor microenvironment significantly limits the therapeutic efficacy of photodynamic therapy (PDT). Herein, a laser-activated drug delivery system is successfully developed for photodynamic-gas synergistic therapy.

Synergistic Strain and Ligand Effects Boosting the Activity of Pt-Based Peroxidase Nanozymes for Femtomolar-Level Colorimetric Immunoassay of Protein Biomarkers.

Sensitive detection of protein biomarkers is crucial for advancing biomedical research and clinical management. Although colorimetric enzyme-linked immunosorbent assays (CELISAs) have been widely recognized as a benchmark technique for protein biomarker detection, their sensitivity is fundamentally constrained by the intrinsic catalytic limitations of conventional enzyme labels. In this study, we present the engineering of high-performance Pt-based peroxidase nanozymes leveraging the synergistic effects of strain and ligand interactions.

Design, Synthesis, and Biological Evaluation of Thieno[3,2-]pyrimidine Derivatives as the First Bifunctional PI3Kδ Isoform Selective/Bromodomain and Extra-Terminal Inhibitors.

The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound () was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC) = 112 ± 8 nM] and BRD4-BD1 (IC = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells.

Novel co-delivery nanomedicine for photodynamic enlarged immunotherapy by cascade immune activation and efficient Immunosuppression reversion.

Photodynamic therapy (PDT) combined with immunotherapy has become a promising antitumor strategy. However, precise regulation of the activation of antitumor immunity and effective reversion of immunosuppressive tumor microenvironment (TME) remains challenging. In this paper, a novel co-delivery nanomedicine is developed to solve these issues for photodynamic amplified immunotherapy.

Discovery and optimization of novel 4-morpholinothieno[3,2-d]pyrimidine derivatives as potent BET inhibitors for cancer therapy.

The identification of structurally novel and potently active BET inhibitors represents a significant advancement in the field of anticancer therapeutics. In the present investigation, leveraging the outcomes of previous screening endeavors, we successfully optimized and synthesized a novel series of bromodomain and extra-terminal (BET) inhibitors with a 4-morpholinothieno[3,2-d]pyrimidine structure. Among the synthesized compounds, compound 6c emerged as a promising candidate, exhibiting exceptional inhibitory activities against various BET isoform proteins, with IC values ranging from 3.

Copper-Catalyzed Radical Sulfonylation: Divergent Construction of C(sp)-Sulfonyl Bonds with Sulfonylhydrazones.

Sulfonylhydrazones have been proven to be versatile synthetic intermediates in a panel of transformations. However, radical sulfonylation with sulfonylhydrazone as sulfonyl radical source is relatively rare. Here, we found that sulfonylhydrazone can serve as a new sulfonyl radical precursor to couple various partners such as arylacetic acids, ene-yne-ketones, and -quinone methides under copper catalysis and microwave irradiation.

Redox-neutral depolymerization of lignin-derived aryl ethers catalyzed by Rh(III)-complexes: a mechanistic insight.

Density functional theory (DFT) calculations at the TPSSh-D3(BJ)/def2-TZVP (SMD, water) level of theory were performed to understand the mechanism of redox-neutral depolymerization of four types of lignin-derived aryl ether dimers catalyzed by rhodium-terpyridine ([Rh]) and a binuclear Rh complex ([2Rh]). The cleavage of the C-O bond in the β-O-4 model compound was initiated by the dehydrogenation of the alcohol moiety into a ketone intermediate, followed by the reductive cleavage of the ether bond, producing phenol and aromatic ketone products. The [Rh]-OH intermediate, generated by the interaction between the Rh-complex and NaOH, facilitated the transformation of the alcohol group to a CO group in the lignin model compound and subsequent H-transfer, selectively forming rhodium-H active species and the ketone intermediate.

IFITM10 Enhance Tumor Angiogenesis and Promotes Cancer Progression through STAT3 Activation.

Background: Humankind have been struggling with colorectal cancer (CRC) for long period with its rapid progression and invasive metastasis. By hyperactivating IL-6/STAT3 signaling, CRC facilitates the capacity of angiogenesis to plunder massive nutrients and develops gradually under harsh condition.

Methods: The Cancer Genome Atlas database was analyzed for acquiring interferon-γ inducible protein 10 () expression levels and their correlation with clinical outcomes.

Dual-mode photothermal/chemiluminescence vertical flow assay for sensitive point-of-care detection of carcinoembryonic antigen using CuAgS@liposome on a filter membrane.

Conventional lateral flow assays based on colorimetry and fluorescence still have shortages in sensitivity and selectivity due to the severe background interference from complex human fluid sample matrices. In this work, CuAgS nanocrystals with high photothermal conversion efficiency and good peroxidase-like activity were synthesized and applied in the construction of a dual-mode near-infrared-photothermal/chemiluminescence (CL) vertical flow assay of carcinoembryonic antigen (CEA). These two-mode principles showed nearly zero background and the synthesized CuAgS exhibited a high photothermal conversion efficiency of 75.

Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression.

Vanadium-doped metal-organic framework@ZnlnS core-shell heterojunction-attenuated photoelectrochemical immunoassay.

Considering that cancer has become the second leading cause of death in humans, it is essential to develop an analytical approach that can sensitively detect tumor markers for early detection. We report an attenuated photoelectrochemical (PEC) immunoassay based on the organic-inorganic heterojunction 10MIL-88B(FeV)/ZnInS (10M88B(FeV)/ZIS) as a photoactive material for monitoring carcinoembryonic antigen (CEA). The 10M88B(FeV)/ZIS heterojunctions have excellent light-harvesting properties and high electrical conductivity, which are attributed to the advantages of both organic and inorganic semiconductors, namely, remarkable photogenerated carrier separation efficiency and long photogenerated carrier lifetime.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically.

Surface plasmon resonance-enhanced photoelectrochemical immunoassay with Cu-doped porous BiWO nanosheets.

The development of rapid screening sensing platforms to improve pre-screening mechanisms in community healthcare is necessary to meet the significant need for portable testing in biomarker diagnostics. Here, we designed a portable smartphone-based photoelectrochemical (PEC) immunoassay for carcinoembryonic antigen (CEA) detection using Cu-doped ultrathin porous BiWO (CuBWO) nanosheets as the photoactive material. The CuBWO nanosheets exhibit a fast photocurrent response and excellent electrical transmission rate under UV light due to their surface plasmon resonance effect (SPR).

Marine bromophenols suppressed choroidal neovascularization by targeting HUWE1 through NF-κb signaling pathway.

Inflammation plays a key role in the progression of choroidal neovascularization (CNV). Regular intravitreal injection of anti-VEGF medication is required for many patients to sustain eye condition as CNV always recurs due to persistent chronic inflammation in the retina and choroid. Marine bromophenols (BDB) have been widely studied due to their diverse bioactivities, including anti-inflammatory effect, though the mechanism of which remained unclear.

An Efficient Synthesis of Naphtho[2,3-]furan-4,9-diones via Visible-Light-Mediated [3+2] Cycloaddition Reaction.

Naphtho[2,3-]furan-4,9-dione is an important privileged structural motif which is present in natural products, drugs, and drug candidates. Herein, visible-light-mediated [3+2] cycloaddition reaction for the synthesis of naphtho[2,3-]furan-4,9-diones and dihydronaphtho[2,3-]furan-4,9-diones has been developed. Under environmentally friendly conditions, a variety of title compounds were delivered in good yields.

Geometric Signatures as Important Factors to Control the Photo-Stabilities of the Phosphorescent Pd(II)/Pt(II) Complexes: A Case Study.

Operation lifetime, as an important parameter, determines the performance of phosphorescent organic light-emitting diodes (OLEDs). Unveiling the intrinsic degradation mechanism of emission material is crucial for improving the operation's lifetime. In this article, the photo-stabilities of tetradentate transition metal complexes, the popular phosphorescent materials, are explored by means of density functional theory (DFT) and time-dependent (TD)-DFT, aiming to illustrate the geometric signatures as important factors to control the photo-stabilities.

Pharmacological Targeting of Bcl-2 Induces Caspase 3-Mediated Cleavage of HDAC6 and Regulates the Autophagy Process in Colorectal Cancer.

Compound , a spiroindoline compound, exhibits antiproliferative capability against cancer cell lines. However, the exact underlying mechanism of this compound-mediated inhibitory capability remains unclear. Here, we showed that compound is an inhibitor of Bcl-2, which suppresses CRC growth by inducing caspase 3-mediated intrinsic apoptosis of mitochondria.

Controlling the Triplet Potential Energy Surface of Bimetallic Platinum(II) Complex by Constructing Structure-Property Relationship: A Theoretical Exploration.

For phosphorescent materials, managing the triplet potential energy surface stands for controlling the phosphorescence quantum yield. However, due to the complexity and variability, the triplet potential energy surface can be managed with difficulty. In this work, a series of bimetallic Pt(II) complexes, namely , , , , , and , are employed as models to construct a relationship between the structures and triplet potential energy surfaces, aiming to achieve meaningful information to manage the triplet potential energy surface.

Carrier-free nanomedicines self-assembled from palbociclib dimers and Ce6 for enhanced combined chemo-photodynamic therapy of breast cancer.

Palbociclib is the world's first CDK4/6 kinase inhibitor to be marketed. However, it is not effective in the treatment of triple negative breast cancer (TNBC) due to the loss of retinoblastoma protein expression. Thus, combinatorial chemotherapy is indispensable for TNBC treatment.

Acid-Promoted Direct C-H Carbamoylation at the C-3 Position of Quinoxalin-2(1)-ones with Isocyanide in Water.

Described herein is a concise and practical direct amidation at the C-3 position of quinoxalin-2(1)-ones through an acid-promoted carbamoylation with isocyanide in water. In this conversion, environmentally friendly water and commercial inexpensive isocyanide were used as a solvent and carbamoylation reagent, respectively. This study not only provides a green and efficient strategy for the construction of 3-carbamoylquinoxalin-2(1)-one derivatives that can be applied to the synthesis of druglike structures but also expands the application of isocyanide in organic chemistry.

Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development.

Background: Enolase 2 (ENO2) is a crucial glycolytic enzyme in cancer metabolic process and acts as a "moonlighting" protein to play various functions in diverse cellular processes unrelated to glycolysis. ENO2 is highly expressed in head and neck squamous cell carcinoma (HNSCC) tissues relative to normal tissues; however, its impact and underlying regulatory mechanisms in HNSCC malignancy remain unclear.

Methods: Molecular alterations were examined by bioinformatics, qRT-PCR, western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation, and ChIP-PCR assays.