Inorganic Chemistry最新文献

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.

Natural killer (NK) cells, initially identified for their rapid virus-infected and leukemia cell killing and tumor destruction, are pivotal in immunity. They exhibit multifaceted roles in cancer, viral infections, autoimmunity, pregnancy, wound healing, and more. Derived from a common lymphoid progenitor, they lack CD3, B-cell, or T-cell receptors but wield high cytotoxicity via perforin and granzymes. NK cells orchestrate immune responses, secreting inflammatory IFNγ or immunosuppressive TGFβ and IL-10. CD56^dim and CD56^bright NK cells execute cytotoxicity, while CD56^bright cells also regulate immunity. However, beyond the CD56 dichotomy, detailed phenotypic diversity reveals many functional subsets that may not be optimal for cancer immunotherapy. In this review, we provide comprehensive and detailed snapshots of NK cells’ functions and states of activation and inhibitions in cancer, autoimmunity, angiogenesis, wound healing, pregnancy and fertility, aging, and senescence mediated by complex signaling and ligand-receptor interactions, including the impact of the environment. As the use of engineered NK cells for cancer immunotherapy accelerates, often in the footsteps of T-cell-derived engineering, we examine the interactions of NK cells with other immune effectors and relevant signaling and the limitations in the tumor microenvironment, intending to understand how to enhance their cytolytic activities specifically for cancer immunotherapy.

Although first-line immunochemotherapy has improved prognosis for patients with advanced esophageal squamous cell carcinoma (ESCC), more effective strategies still require further investigation. This multi-center, phase II study (ClinicalTrials.gov NCT05013697) assessed the feasibility of benmelstobart (a novel PD-L1 inhibitor) plus anlotinib (multitargeted TKI) and chemotherapy in advanced or metastatic/recurrent ESCC. Eligible patients received 4–6 cycles (21-day) of benmelstobart (1200 mg), anlotinib (10 mg) plus paclitaxel (135 mg/m²)/cisplatin (60–75 mg/m²), then maintained with benmelstobart and anlotinib. Primary endpoint was progression-free survival (PFS) assessed according to RECIST v1.1. Secondary endpoints were tumor response, overall survival (OS), and safety assessed by adverse events (AEs). From September 2021 to November 2023, 50 patients were enrolled and received study treatment. With median follow-up of 23.7 months as of April 1, 2024, median PFS was 14.9 months (95% CI, 11.4-not estimable [NE]) and the 1-year PFS was 58.5% (95% CI, 41.9%–71.9%). Among 50 patients, confirmed objective response rate was 72.0% and disease control rate was 84.0%. Median duration of response of 36 responders was 16.2 months (95% CI, 10.2-NE). At the cutoff date, 31 patients remained alive; median OS was not reached (95% CI, 13.2 months-NE) with 1-year OS of 74.8% (95% CI, 59.8%–84.8%). Forty-six (92.0%) patients reported treatment-related AEs, with 37 (74.0%) were grade ≥3. Overall, benmelstobart plus anlotinib and chemotherapy showed promising efficacy and acceptable toxicity in advanced or metastatic/recurrent ESCC.

Two new dioxidovanadium(V) compounds with the general formula [V^VO₂(L)] (L = hydrazone ligand) were synthesized using three different methods (acidic, neutral, and basic media) with either V^IVOSO₄. 5H₂O, [V^IVO(acac)₂], or NH₄V^VO₃ as the starting material and hydrazone ligands. In both cases, five coordinated V⁵⁺ ions adopted distorted square pyramidal geometry through the coordination of two oxido ligands and one hydrazone ligand. In compound 1, the presence of free hydroxyl groups stabilized the molecular species through intramolecular O–H•••N type hydrogen bond interactions. In compound 2, the free amino groups are involved in both intramolecular N–H•••N type and intermolecular N–H•••O type hydrogen bond interactions. Compound 1 showed highly selective luminescence turn-on behavior, along with a 33-nm blue shift in the presence of Al³⁺ ions in an aqueous medium. The experimental limit of detection (LOD) was found to be 66 nM. Whereas compound 2 showed luminescence quenching behavior in the presence of Fe³⁺, Al³⁺, and Cr³⁺ ions. The LODs were observed to be 312, 408, and 280 nM for Fe³⁺, Al³⁺, and Cr³⁺ ions, respectively. The luminescence response mechanisms of both compounds in the presence of metal ions have been correlated with molecular-level interactions.

A recent study published in Signal Transduction and Targeted Therapy by Wenjing Z. and Min Y. et al. presents a potential game-changer in the field of chronic hepatitis B infection. The research focuses on the delivery of multiplexed RNAs using lipid nanoparticles, exploring the synergistic effects of dual small interfering RNAs (siRNAs) targeting the hepatitis B virus (HBV) alongside modulating immune responses with interleukin-2 (IL-2) mRNA.¹

In a recent study published in Nature, Lynch et al.¹ reported a consistent spatial expansion of the resting state salience network in subjects with major depression. The expansion was already present in children who later developed depression and remained stable over time in patients with depression, indicating a trait-like behavior of the observed endophenotype.

In a recent article published in Science, Szeto et al. identified myocyte-specific enhancer factor 2d (Mef2d) as a promoter of type 2 immunity and allergic lung inflammation. Using CRISPR screens and orthogonal recombinase-enabled Boolean gene circuitry, the authors revealed that Mef2d modulates GATA3 expression by suppressing Regnase-1, thereby boosting IL-33 signaling and cytokine production.¹