Covalent organic frameworks (COFs), a class of porous crystalline organic polymers, have emerged as promising materials for photocatalysis. Structural functionalization of COFs is an effective strategy to improve their photocatalytic performance. However, this approach is mainly limited within interior parts of COFs. Herein we report exterior functionalization of a one-dimensional (1D) COF by introducing terpyridine units on its edges to anchor Pt(ii) cations. The as-obtained 1D COF (Pt-Tpy-COF) exhibits high photocatalytic activity for hydrogen evolution from water, with a hydrogen evolution rate up to 7.8 mmol g-1 h-1. Experimental studies and theoretical calculations reveal that the high performance of Pt-Tpy-COF benefits from its distinct 1D framework with readily accessible active sites. This study not only demonstrates the potential of 1D COFs as photocatalysts, but also provides valuable insights for the design and development of highly efficient catalysts for various catalytic applications based on the structural features of this new type of nanoporous crystalline framework materials. Exterior functionalization of a one-dimensional (1D) covalent organic framework (COF) was achieved by introducing terpyridine units on its edges to anchor Pt(ii) cations. It exhibits high photocatalytic activity for hydrogen evolution from water.

The nucleophilic aromatic substitution (SNAr) between heteroaryl halides (Cl, Br) and thiols proceeds smoothly in DMAc under the action of K2CO3 at rt-100 degrees C. For most electron-deficient heteroarenes, reaction takes place without introducing an additional electron-withdrawing group. For electron-rich heteroarenes, an additional electron-withdrawing group such as a simple ester, keto, cyano, and nitro group is required to ensure the reaction completes. The reactivity trend of heteroaryl halides is highly dependent on the electronic nature of the heteroarenes and orientation of halogens. Besides thiols, a couple of functionalized thioureas and thioamides are compatible with these conditions, providing the corresponding heteroaryl thioethers in good yields.

A novel 1,2,3-triazole-based green oxidizer 4-nitro-2,5-bis(trinitromethyl)-1,2,3-triazole (JY-23) with high oxygen balance (OBco2 = +23.3%) was synthesized in 5 steps from 4-cyano-5-nitro-1H-1,2,3-triazole. Its structure was confirmed by NMR, IR, elemental analysis and single crystal X-ray diffraction. It exhibits a high density (1.931 g cm-3), a high positive enthalpy of formation (Delta fH = +294.81 kJ mol-1), and acceptable mechanical sensitivities (IS = 11 J and FS = 42 N), and, importantly, it is non-hydroscopic. The contribution of JY-23 to the specific impulse of solid propellants as a replacement for ammonium perchlorate (AP) in typical HTPB (hydroxyl terminated polybutadiene) and GAP (glycidyl azide polymer) solid propellants was calculated using NASA-CEA software. The results show that the replacement of AP with JY-23 results in a much higher specific impulse compared to some previously reported oxidizers, suggesting its potential application as a green oxidizer to replace AP in solid propellants. A triazole compound (JY-23) with the largest number of nitro groups (seven nitro groups) was designed and synthesized.

Aim: To develop a robust drug-delivery system using multi-arm amphiphilic block copolymers for enhanced efficacy in cancer therapy. Materials & methods: Two series of amphiphilic polymer micelles, PEG-b-PCLm and PEG-b-PCLm/TPGS, were synthesized. Doxorubicin (DOX) loading into the micelles was achieved via solvent dialysis. Results: The micelles displayed excellent biocompatibility, narrow size distribution, and uniform morphology. DOX-loaded micelles exhibited enhanced antitumor efficacy and increased drug accumulation at tumor sites compared with free DOX. Additionally, 4A-PEG(47)-b-PCL21/TPGS micelles effectively suppressed drug-resistant MCF-7/ADR cells. Conclusion: This study introduces a novel micelle formulation with exceptional serum stability and efficacy against drug resistance, promising for cancer therapy. It highlights innovative strategies for refining clinical translation and ensuring sustained efficacy and safety in vivo.

2,3-Allenyl amines have shown wide applicability in biomedical and synthetic applications. Due to their enormous potential for applications, researchers have been dedicated to the development of methods for synthesizing 2,3-allenyl amines. Herein, a palladium-catalyzed three-component reaction of 2-alkynyl-1,4-diol dicarbonates, organoboronic acids, and nitrogen nucleophiles forming 2,3-allenyl amines with excellent regio- and chemo-selectivity has been developed. Substrate compatibility and synthetic applications have been demonstrated. Control experiments supported a mechanism involving 1,2,3-triene-Pd species and methylene-pi-allyl palladium species.

Fibroblast growth factor receptor 2 (FGFR2) represents an appealing therapeutic target for multiple cancers, yet no selective FGFR2 inhibitors have been approved for clinical use to date. Here, we report the discovery of a series of new selective, irreversible FGFR2 inhibitors. The representative compound LHQ490 potently inhibited FGFR2 kinase activity with an IC 50 of 5.2 nM, and was >61-, >34-, and >293 -fold selective against FGFR1, FGFR3, and FGFR4, respectively. LHQ490 also exhibited high selectivity in a panel of 416 kinases. Cell -based studies revealed that LHQ490 efficiently suppressed the proliferation of BaF3-FGFR2 cells with an IC 50 value of 1.4 nM, and displayed >70- and >714 -fold selectivity against BaF3-FGFR1 and the parental BaF3 cells, respectively. More importantly, LHQ490 potently suppressed the FGFR2 signaling pathways, selectively inhibited FGFR2-driven cancer cell proliferation, and induced apoptosis of FGFR2-driven cancer cells. Taken together, this study provides a potent and highly selective FGFR2 inhibitor for further development of FGFR2targeted therapeutic agents.

OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families. The molecular basis of OSCA/TMEM63 channel mechanosensitivity was investigated by determining 44 cryogenic electron microscopy structures of channels in different environments, expanding understanding of channel-mediated mechanotransduction and pore formation, with implications for two protein families.

Purpose of reviewHypertension, commonly known as high blood pressure, is a widespread health condition affecting a large number of individuals across the globe. Although lifestyle choices and environmental factors are known to have a significant impact on its development, there is growing recognition of the influence of genetic factors in the pathogenesis of hypertension. This review specifically focuses on the hereditary causes of hypertension that are associated with increased sodium transport through the thiazide-sensitive NaCl cotransporter (NCC) or amiloride-sensitive epithelial sodium channel (ENaC), crucial mechanisms involved in regulating blood pressure in the kidneys. By examining genetic mutations and signaling molecules linked to the dysregulation of sodium transport, this review aims to deepen our understanding of the hereditary causes of hypertension and shed light on potential therapeutic targets.Recent findingsLiddle syndrome (LS) is a genetic disorder that typically manifests early in life and is characterized by hypertension, hypokalemic metabolic alkalosis, hyporeninemia, and suppressed aldosterone secretion. This condition is primarily caused by gain-of-function mutations in ENaC. In contrast, Pseudohypoaldosteronism type II (PHAII) is marked by hyperkalemia and hypertension, alongside other clinical features such as hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. PHAII results from overactivations of NCC, brought about by gain-of-function mutations in its upstream signaling molecules, including WNK1 (with no lysine (K) 1), WNK4, Kelch-like 3 (KLHL3), and cullin3 (CUL3).SummaryNCC and ENaC are integral components, and their malfunctions lead to disorders like LS and PHAII, hereditary causes of hypertension. Current treatments for LS involve ENaC blockers (e.g., triamterene and amiloride) in conjunction with low-sodium diets, effectively normalizing blood pressure and potassium levels. In PHAII, thiazide diuretics, which inhibit NCC, are the mainstay treatment, albeit with some limitations and potential side effects. Ongoing research in developing alternative treatments, including small molecules targeting key regulators, holds promise for more effective and tailored hypertension solutions.