Photoinduced synthesis of trisubstituted allylic molecules migratory allylation of olefins.

A transition-metal-free method to afford diverse trisubstituted allylic molecules migratory allylation of olefins under light irradiation is described. This system tolerated diverse -tosylhydrazones and olefinic boronic acids. Successful allylation of drugs and natural-product analogues was achieved.

Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation.

Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.

TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy.

As a critical member of the Coronin family, Coronin 1A (CORO1A) plays a crucial role in the progression of triple-negative breast cancer (TNBC). However, CORO1A is typically considered "undruggable" due to its smooth surface and complex protein-protein interactions (PPIs). Molecular glues have emerged as one of the most effective strategies to rapidly degrade such "undruggable" targets.

Integration of feature-based molecular networking and high-definition data-dependent acquisition for the comprehensive multicomponent characterization of Honghua Xiaoyao Tablet.

Systematically identifying the chemical constituents in complex matrices is a challenge due to the inherent characteristics of compounds. The combination of liquid chromatography-tandem mass spectrometry (LC-MS) and classical molecular networking (CLMN) is a powerful technology for annotating small molecules. However, the low coverage from inappropriate acquisition modes and the inseparability of isomeric compound nodes still hinders the comprehensive metabolite characterization.

Xanthate Disulfide-Mediated RAFT Polymerization Toward Oxygen Tolerance.

In recent years, the fully oxygen-tolerant reversible addition-fragmentation chain transfer (RAFT) polymerization has been emerging as a versatile and powerful tool for preparing well-defined polymers. In this contribution, the symmetrical diethyl xanthogen disulfide (XD) is successfully used as an initiator, chain transfer agent, and termination (iniferter) agent to directly regulate the open-to-air RAFT polymerization. The high end-group fidelity of polymer demonstrated by nuclear magnetic resonance (H-NMR) and matrix-assisted laser desorption/ionization time-of-flight mass spectra indicates that sulfur-centered xanthate radical can initiate and regulate RAFT polymerization of methacrylate (MA) under open conditions.

Preschool age-specific obesity and later-life kidney health: a Mendelian randomization and colocalization study.

Objectives: While the association between obesity and kidney diseases has been found in previous studies, the relationship between preschool-age obesity and later-life kidney health remains unclear, posing challenges for effective interventions in this critical life period.

Methods: Utilizing the hitherto largest genome-wide association studies, we conducted two-sample mendelian randomization (MR) to estimate the association of preschool age-specific obesity on kidney health and diseases, including blood urea nitrogen (BUN), eGFRcrea, eGFRcys, chronic kidney disease (CKD), IgA nephropathy, and diabetic nephropathy. Then, we applied multivariable Mendelian randomization (MVMR) and stepwise MR to elucidate the role of adult obesity and 12 other potential factors in the pathway between preschool age-specific obesity and kidney health.

Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity targeting USP22.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs.

Multi-omics and network pharmacology approaches reveal Gui-Ling-Ji alleviates oligoasthenoteratozoospermia by regulating arachidonic acid pathway.

Background: Gui-Ling-Ji (GLJ) described in the ancient medical book 'Yunji Qijian' is a traditional Chinese medicine formula used to improve male fertility. It is now available for the treatment of oligoasthenoteratozoospermia (OAT). However, the active ingredients and mechanism of GLJ are not clear.

Catalytic Enantioselective Synthesis of Boron-Stereogenic and Axially Chiral BODIPYs via Rhodium(II)-Catalyzed C-H (Hetero) Arylation with Diazonaphthoquinones and Diazoindenines.

The molecular engineering of boron dipyrromethenes (BODIPYs) has garnered widespread attention due to their structural diversity enabling tailored physicochemical properties for optimal applications. However, catalytic enantioselective synthesis of structurally diverse boron-stereogenic BODIPYs through intermolecular desymmetrization and BODIPYs with atroposelectivity remains elusive. Here, we showcase rhodium(II)-catalyzed site-specific C-H (hetero)arylations of prochiral BODIPYs and polysubstituted BODIPYs with diazonaphthoquinonesand diazoindenines, providing efficient pathways for the rapid assembly of versatile (hetero)arylated boron-stereogenic and axially chiral BODIPYs through long-range desymmetrization and axial rotational restriction modes.

Liver-expressed antimicrobial peptide 2 is a hepatokine regulated by ghrelin, nutrients, and body weight.

Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide that counteracts the hunger hormone ghrelin-induced functions. Recently, we showed that vertical sleeve gastrectomy (VSG) did not alter the serum LEAP2 concentration in individuals with obesity. Here, we investigated the effects of VSG in both chow diet (CD)-fed and high-fat diet (HFD)-fed mice.

Aβ -induced excessive mitochondrial fission drives type H blood vessels injury to aggravate bone loss in APP/PS1 mice with Alzheimer's diseases.

Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with bone homeostasis. However, few studies have concentrated on bone vascular alteration and its role in AD-related bone loss.

Experimental studies on the cooling and heating performance of a highly emissive coating.

In this study, the cooling effect below ambient air temperature, heat dissipation properties and heating energy efficacy of a superomniphobic self-cleaning (SSC) highly emissive (HE) coating were systematically investigated. Except at midday, the SSC-HE coating with an extremely high solar reflectance of 0.985 showed a better cooling effect than a 10-cm-thick polyurethane insulation layer.

In-Depth Analysis of Molecular Network Based on Liquid Chromatography Coupled with Tandem Mass Spectrometry in Natural Products: Importance of Redundant Nodes Discovery.

The identification of molecules within complex mixtures is a major bottleneck in natural products (NPs) research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as the main tool for the high-throughput characterization of NPs. The large amount of data sets by LC-MS/MS presents a challenge for data processing and interpretation, and the LC-MS/MS molecular network (MN) is one of the most prominent tools for analyzing large MS/MS data sets, widely used for rapid classification, identification, and structural speculation of unknown compounds.

Insights into therapeutic peptides in the cancer-immunity cycle: Update and challenges.

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy. As vital biological mediators, peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies (CITs). However, physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.

Deciphering the role of PLCD3 in lung cancer: A gateway to glycolytic reprogramming via PKC-Rap1 activation.

PLCD3 belongs to the phospholipase C delta group and is involved in numerous biological functions, including cell growth, programmed cell death, and specialization. However, the role of PLCD3 in lung cancer still needs further investigation. This research aimed to investigate if PLCD3 influences glycolytic reprogramming and lung cancer development through the PKC-dependent Rap1 signaling pathway.

Explainable Fault Diagnosis Using Invertible Neural Networks-Part I: A Left Manifold-Based Solution.

The series includes two parts, articulating the two novel avenues of research on intelligent fault diagnosis (FD) for nonlinear feedback control systems. In Part I of the series, we design a novel FD paradigm by elaborating an invertible neural network (INN) for feedback control systems. With the aid of a left manifold, the core idea behind the INN-based FD scheme is as follows: 1) formulation of residual generator used for FD as a projection of system data onto the null space that has the same dimension as system outputs; 2) in a topological space, elaboration of a homeomorphism that delivers an invertible relationship between system outputs and residual signals when the system input is given; and 3) skillful introduction of both the master and slave objective functions to achieve system/parameter identification with information loseless property.