Non-proliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy, is a leading cause of visual impairment in patients with type 2 diabetes mellitus, characterized by retinal microaneurysms, hemorrhages, exudates, and macular edema. Conventional Western therapies, while partially effective, often carry limitations such as high costs, potential adverse effects, and incomplete control of disease progression, creating an unmet clinical need for safer and more comprehensive treatment options. Compound danshen dripping pills (CDDP), a patented traditional Chinese medicine formulation composed of extracts from Radix Salviae Miltiorrhizae (danshen) and Radix Panax Notoginseng (sanqi), has been widely used in clinical practice for decades to manage cardiovascular and microvascular disorders, and emerging evidence suggests its potential in NPDR management. This review synthesizes the latest findings from more than 65 published studies, including randomized controlled trials, meta-analyses, network meta-analyses, preclinical investigations, and molecular studies, to comprehensively evaluate CDDP's efficacy, safety, and underlying mechanisms in NPDR; discusses CDDP's multi-targeted effects on key pathophysiological pathways of NPDR, including oxidative stress, inflammation, and microvascular dysfunction, and explores its synergistic effects when combined with conventional Western therapies; and highlights critical research gaps and outline future directions to validate CDDP's utility and facilitate its integration into global clinical guidelines for NPDR management. The accumulated evidence confirms that CDDP is a safe and effective therapeutic option for NPDR, with a favorable safety profile and multi-faceted mechanisms of action, though further high-quality research is needed to address limitations in current studies and expand its clinical application.

Developing highly efficient and stable catalysts for hydroxylamine nitrate (HAN) decomposition is challenged by their tendency to sinter and suffer a sharp loss in specific surface area at high temperatures. Herein, a series of manganese-substituted lanthanum hexaaluminate (LM(x)A, x = 0, 0.5, 1, 2, 3) nanomaterials were prepared by coprecipitation-decarbonization templating method, and the effect of manganese doping on structure and the catalytic activity for HAN decomposition were systematically investigated. XRD and BET characterization revealed that the manganese substitution significantly regulated the structural properties of hexaaluminate nanomaterials, among which pure-phase LaMnAl11O19 (denoted as LM(1)A) exhibited excellent high-temperature structural stability. After calcination at 1400 degrees C for 12 h, the grain size increased only slightly from 24.1 to 28.7 nm, and the specific surface area retained at 15.8 m(2)& centerdot;g(-1), indicating outstanding resistance to nanoparticle sintering. Notably, LM(1)A served dual roles as both a catalytic support and an active component, exhibiting a stable catalytic efficiency for HAN decomposition, which could significantly reduce the initial decomposition temperature from 162.0 degrees C (thermal decomposition) to 120.4 degrees C. Manganese doping lowers the reaction energy barrier, as confirmed by critical kinetic parameters. Rational nanoscale regulation of manganese doping in hexaaluminate significantly enhances the high-temperature stability, providing an important reference for the development of highly efficient and long-life HAN decomposition catalysts.

One-step ethylene copolymerization with readily available short-chain alkenyl phenols is an attractive alternative to post-modification or the use of designed phenolic comonomers for preparing phenol-functionalized polyethylenes, yet prior examples have largely relied on early transition-metal catalysts or phosphine-sulfonate Pd systems and typically afford linear backbones. Here we report binuclear Ni-catalyzed ethylene copolymerization with 2-allylphenol enabled by Et2AlCl, which serves as both a cocatalyst and an effective pretreatment reagent for the protic comonomer. Under 1 atm ethylene, phenol-functionalized branched polyethylenes are obtained with activities up to 1200 kg (mol cat h atm)(-1), M-n = 19.1-84.1 kg mol(-1), phenolic incorporation of 0.5-2.7 mol%, and branching densities of 78-99 CH3/1000C. Varying Et2AlCl pretreatment, comonomer concentration and temperature reveals coupled trade-offs between incorporation and productivity/M-n. NMR analysis further reveals both in-chain and chain-end incorporation motifs of the phenolic comonomer.

Carboxylic acids are a class of chemicals with abundant sources, structural diversity, stability, and costeffectiveness, representing the second largest class of commercially available organic building blocks after amines. The past decade has witnessed the rapid development of photoinduced radical decarboxylative transformation of alkyl carboxylic acids. However, the progress in the decarboxylative transformation of aryl carboxylic acids is slow, mianly due to the relatively reluctant decarboxylation of O-centered aryl carboxylate radicals and the subsequent very reactive aryl radicals, suffering severe competitive pathways. In the latest five years, ligand-to-metal charge transfer (LMCT)-driven photoinduced metalcatalyzed/mediated decarboxylative transformation of aryl carboxylic acids (carboxylates) has gained some achievements, such as copper-catalyzed/mediated halogenation, hydroxylation, sulfoximination, borylation, halosulfonylation, thianthrenation, allylation, thiolation and hydrogenation, iron-catalyzed thiolation and bromination. Further development is highly expected to realize new types of reactions through smart design and control of reaction conditions. For instance, the merger of LMCT and transition metal catalysis might provide an opportunity to achieve the decarboxylative cross-coupling of aryl carboxylic acids.

Asymmetric carbothiolation of alkenes represents a highly efficient, yet underexplored, strategy for the direct construction of chiral thioethers. Herein, we report a palladium-catalyzed enantio- and regio-selective carbothiolation of alkenes via C-S bond activation and migratory insertion. Leveraging a chiral N-heterocyclic carbene ligand, this method provides access to chiral indole derivatives featuring quaternary stereocenters atom-, step-, and redox-economically. The reaction is applicable to a broad range of substrates, providing the corresponding products in up to 99% yield and up to 97% e.e.. Mechanistic investigations reveal that oxidative addition of the C-S bond is the enantio-determining step, while the subsequent reductive elimination serves as the rate-determining step.

Here, we report a nickel-catalyzed remote substitution of unprotected alkenyl alcohols with arylboronic acids, enabling C-C bond formation at positions distal to the hydroxyl group. Unlike conventional substitution reactions, which occur at the original or allylic position of a leaving group and typically require preactivation, this strategy directly exploits native alcohols and forges bonds that are remote from the hydroxyl site. The reaction overcomes the intrinsic preference for beta-H elimination by selectively promoting beta-OH elimination through a novel ligand-enabled process. A bulky 1,3-diketone ligand enhances the oxophilicity of nickel probably via reversible keto-enol tautomerization and orchestrates alkene carbo-nickelation, controlled metal migration, and exclusive beta-OH elimination. The method operates under mild and redox neutral conditions with excellent regioselectivity, broad functional-group tolerance, and compatibility with alkenyl alcohols of varying chain lengths.

Electron donor-acceptor (EDA) acceptor catalysis remains significantly less developed than donor catalysis. Herein, a hydrogen-bond-mediated EDA acceptor catalysis using readily available 4,4'-di-tert-butyl-2,2'-bipyridine (dtbbpy) or 4-tert-butylpyridine as the acceptor catalyst is developed, enabling the hydrosulfonylation of unactivated olefins and sulfonyl dehydrogenation of styrenes, utilizing sodium sulfinates as the sulfonyl source. The reaction proceeds under mild conditions. A broad range of functional groups is well tolerated, affording good to excellent yields. Preliminary mechanistic investigations, including both computational studies and experiments, indicate that hydrogen bonding between sulfinic acid and the acceptor catalyst may facilitate the formation of a photoresponsive EDA complex and the subsequent photo-induced radical generation.

A practical method for the fluoroalkylthiolation of arenes has been developed using fluoroalkanesulfinyl chlorides as fluoroalkylthiolating reagents and PCl3 or PCl3/SnCl4 as the promoter. A series of fluoroalkylthiolated arenes were obtained in moderate to high yields under mild conditions. The reaction of highly activated arenes worked smoothly in the presence of PCl3 at room temperature, while less nucleophilic arenes required cooperative promotion of PCl3 and SnCl4 at higher temperature. Based on F-19 NMR monitoring of the reaction systems, two plausible reaction pathways were proposed, involving either a fluoroalkylsulfinylated intermediate or a fluoroalkanesulfenyl chloride species.

Pyridoxal 5 '-phosphate (PLP)-dependent enzymes represent one of the most functionally diverse families of biocatalysts, mediating a variety of bond transformations associated with amino acids. However, catalytic strategies that enable C-C bond cleavage at remote positions within amino acids remain exceedingly rare. Recently, we identified Fgm3, an unusual PLP-dependent enzyme in Fusarium graminearum, which catalyzes the C beta-C gamma bond cleavage of 4(S)-hydroxy-l-arginine, yielding l-alanine and guanidino acetaldehyde during the biosynthesis of the fungal virulence factor fusaoctaxin B. Here, using X-ray crystallography, site-specific mutagenesis, and theoretical computation, we provide evidence that rationalizes the retro-aldol-like reaction catalyzed by Fgm3. We determined six high-resolution crystal structures of Fgm3, in complex with PLP and either its substrate, a substrate analog, or its product. These structures reveal a preorganized substrate-binding pocket that can anchor the alpha-carboxylate and guanidino for precise recognition. Combined structural and mutational analyses identified residue His116 as the key catalytic base responsible for gamma-hydroxyl deprotonation to trigger C beta-C gamma bond cleavage. Theoretical computation delineates the catalytic energy landscape and accordingly supports a synergistic catalytic mechanism in which His116 orchestrates proton transfer and C-C bond breaking. These findings establish the molecular basis of Fgm3-mediated C-C cleavage, expand the repertoire of PLP enzymology, and provide a blueprint for engineering biocatalysts to access noncanonical amino acids.

Systemic autoinflammatory diseases (SAID) with inborn errors of cell death (IECD) are caused by overactivation of programmed cell death (PCD). However, the pathogenesis by which PCD leads to autoinflammation remains unclear. Here, we identified IECD patients carrying compound heterozygous RIPK1 variants K377E/R390G with autoinflammatory manifestations. Mechanistically, K377E and R390G mutations suppress NF-kappa B signaling and activate RIPK1 to promote cell death. CD8(+) T cells of the patients displayed overactivated RIPK1 and excessive cell death, leading to an elevated CD4/CD8 ratio, which could also be detected in patients with cleavage-resistant mutation of RIPK1 or SHARPIN deficiency. We show that the increased cell death of CD8(+) T cells promotes TNF and IFN-gamma secretion to activate monocytes/macrophages, which triggers overproduction of proinflammatory cytokines. In addition, disruption of the communication between T cells and monocytes/macrophages through pharmacologic blockade of TNF and IFN attenuates proinflammatory cytokine production in macrophages and relieves all the symptoms in patients. This study further clarifies the mechanism for a group of IECD with SAID. Increased CD4/CD8 ratio and augmented RIPK1 activation in T cells provide potentially additional criteria for diagnosis of RIPK1-dependent IECD and a combination of TNF/JAK inhibitor could be an effective therapy for the diagnosed patients.