Inorganic Chemistry最新文献

UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.

Ordered intermetallics contribute to a unique class of catalyst materials due to their rich atomic features. Further engineering of ordered intermetallics at a mesoscopic scale is of great importance to expose more active sites and introduce new functions. Recently, multidimensionally ordered mesoporous intermetallic (MOMI) nanoarchitectonics, which subtly integrate atomically ordered intermetallics and mesoscopically ordered mesoporous structures, have held add-in synergies that not only enhance catalytic activity and stability but also optimize catalytic selectivity. In this tutorial review, we have summarized the latest progress in the rational design, targeted synthesis, and catalytic applications of MOMIs, with a special focus on the findings of our group. Three strategies, including concurrent template route, self-template route, and dealloying route, are discussed in detail. Furthermore, physicochemical properties and catalytic performances for several important reactions are also described to highlight the remarkable activity, high stability, and controllable selectivity of MOMI nanoarchitectonics. Finally, we conclude with a summary and explore future perspectives in the field to contribute to wider applications.

In a recent paper published in Nature, Mathys and co-workers presented a comprehensive and precise transcriptomic atlas of distinct brain regions from individuals with and without Alzheimer’s disease (AD). This paper aimed to identify differences in regional molecular architecture along with region-specific changes in neuronal and glial subtypes, while also investigating whether certain brain regions and cell subtypes are more vulnerable or uniquely affected by AD compared to others, and exploring mechanisms that may contribute to cellular resilience.¹

A recent study published in Nature by Roje, Zhang and colleagues highlights the emergent role gut microbiota play in processing environmental carcinogens and raises its potential as a target for reducing cancer risk in humans.¹ This study fills yet another piece into the giant jigsaw puzzle that illustrates the central role of the dynamic structure and function of the intestinal microbiome in cancer pathogenesis and therapy efficacy.

In a landmark study recently published in Cell, Berger et al. demonstrated that computationally designed miniproteins could serve as novel, orally available treatment strategies by specifically targeting cytokine signaling pathways through the potent inhibition of ligand-receptor interactions in the body.¹ This breakthrough study unveils the potential for miniprotein-based therapies to revolutionize molecular treatment strategies for autoimmune diseases and cancers.

This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF⁺ cells and CD4⁺Foxp3⁺ Treg cells, and increased perivascular CD4⁺ T cells, CD39⁺CD8⁺ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).