Design and structural optimization of novel SOS1 inhibitors in KRAS-driven cancers.

The development of small molecular inhibitors to target the guanine nucleotide exchange factor SOS1 has been proved to be a hopeful strategy for the treatment of various KRAS-driven cancers. Constructing novel SOS1 inhibitors is urgently needed due to the increasing drug resistance arising from structural similarity of earlier analogs. Herein, we discovered a new SOS1 inhibitor with para-dimethylaminoazetidine quinazoline scaffold.

Diastereoselective Radical Cyclization of Imine and Olefin: Rapid Access to 1,2,3,4-Tetrahydroquinoline Scaffolds.

Herein, we developed an intramolecular radical cyclization reaction between imines (or aldehydes) and olefins using Hantzsch ester as the reductant to enable the efficient and diastereoselective synthesis of 1,2,3,4-tetrahydroquinoline scaffolds with a high medicinal value. Deuteration experiments indicated that the radical intermediate abstracts a hydrogen atom directly from the 4 position of the Hantzsch ester, thereby ruling out the possibility of an anionic intermediate formation via the radical crossover pathway. A fast synthesis of BRD4 degraders and the elucidation of their cellular and enzymatic activities demonstrate the practicality of this method.

Ligand-Controlled Enantioselective and Regiodivergent Construction of 1,2- and 1,3-Disubstituted Alicycles.

Three-dimensional alicyclic skeletons with multiple stereochemically defined chiral centers are highly valuable in modern drug discovery. Here, we reported a diverse approach to access 1,2- and 1,3-disubstituted chiral cycloalkanes by the strategy of NiH-catalyzed, transannular-directed alkene desymmetrization. The ring strain of the bridged bicyclic organonickel intermediate and the coordination effect of the ligand were identified as crucial factors in determining site selectivity by influencing the NiH migration step.

Deoxygenative radical cross-coupling of C(sp)-O/C(sp)-H bonds promoted by hydrogen-bond interaction.

Building C(sp)-rich architectures using simple and readily available starting materials will greatly advance modern drug discovery. C(sp)-H and C(sp)-O bonds are commonly used to strategically disassemble and construct bioactive compounds, respectively. However, the direct cross coupling of these two chemical bonds to form C(sp)-C(sp) bonds is rarely explored in existing literature.

A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates.

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN (MIC = 0.001 mM) exhibited a potent antifungal activity against , which is 13-fold higher than that of fluconazole.

One-step growth of Cu-doped carbon dots in amino-modified carbon nanotube-modified electrodes for sensitive electrochemical detection of BPA.

Copper-doped carbon dots and aminated carbon nanotubes (Cu-CDs/NH-CNTs) nanocomposites were synthesized by a one-step growth method, and the composites were characterized for their performance. An electrochemical sensor for sensitive detection of bisphenol A (BPA) was developed for using Cu-CDs/NH-CNTs nanocomposites modified with glassy carbon electrodes (GCE). The sensor exhibited an excellent electrochemical response to BPA in 0.

Sterically Hindered Oleogel-Based Underwater Adhesive Enabled by Mesh-Tailoring Strategy.

Underwater adhesives hold significant relevance in daily life and numerous industrial applications. Despite considerable efforts, developing scalable, high-performance underwater adhesives through a simple and effective method remains a formidable challenge. This study presents a novel mesh-tailoring strategy for in situ, rapid, and ultrastrong oleogel-based underwater adhesives (OUA), which comprises a highly crosslinked polyurethane network with a matching mesh size (≈2.

Clinical usefulness of linked color imaging in identifying infection: A systematic review and meta-analysis.

Background: Accurate diagnosis of () infection status is a crucial premise for eradication therapy, as well as evaluation of risk for gastric cancer. Recent progress on imaging enhancement endoscopy (IEE) made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict infection in real time. As a novel IEE modality, linked color imaging (LCI) has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone.

Platelet-rich plasma promotes skeletal muscle regeneration and neuromuscular functional reconstitution in a concentration-dependent manner in a rat laceration model.

Abnormal function of injured muscle with innervation loss is a challenge in sports medicine. The difficulty of rehabilitation is regenerating and reconstructing the skeletal muscle tissue and the neuromuscular junction (NMJ). Platelet-rich plasma (PRP) releases various growth factors that may provide an appropriate niche for tissue regeneration.

Design, Synthesis, and Insecticidal and Fungicidal Activities of Ether/Oxime-ether Containing Isoxazoline Derivatives.

The existing agricultural insecticides have developed drug resistance from long-term use. Isoxazoline derivatives are new insecticides discovered in the 21st century. Because of their unique insecticidal mechanism, high selectivity, safety, and no significant cross resistance with the existing pesticides on the market, they have become a hot spot in the field of pesticide research.

Non-isocyanate Polyurethane Coating with High Hardness, Superior Flexibility, and Strong Substrate Adhesion.

Flexible hard coatings with strong adhesion are critical requirements for several foldable devices and marine applications; however, only a few such coatings have been reported. Herein, we report a non-isocyanate polyurethane (NIPU) coating prepared by the epoxy-oligosiloxane nanocluster-amine curing reaction and cyclic carbonate-amine polyaddition, where the former provides the coating with ceramic-like hardness and polymer-like flexibility while the latter polymerization results in NIPU with strong substrate adhesion. The coating is transparent (>92% transmittance), hard (5-7 H), and flexible (2 mm bending diameter).

Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments.

The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including , and 22019.

An unanticipated discovery of novel naphthalimidopropanediols as potential broad-spectrum antibacterial members.

Constructing a new antibacterial structural framework is an effective strategy to combat drug resistance. This work discovered a class of naphthalimidopropanediols (NIOLs) as a novel structural type of potential broad-spectrum antibacterial agents. Especially, NIOLs 9u, 12i, 15 against Staphylococcus aureus and NIOLs 9l, 13a against Pseudomonas aeruginosa showed excellent inhibitory activities, and they displayed high membrane selectivity from an electrostatic distinction on the membranes between bacteria and mammalian cells.

Coumarin thiazoles as unique structural skeleton of potential antimicrobial agents.

A novel type of coumarin thiazoles as unique multi-targeting antimicrobial agents were developed through four steps including cyclization, nucleophilic substitution and condensation starting from commercial resorcine. Most of the prepared coumarin thiazoles displayed favorable inhibitory potency against the tested strains. Noticeably, methyl oxime V-a exerted potent inhibitory efficacy against methicillin-resistant Staphylococcus aureus (MRSA) at low concentration (1 μg/mL) and showed broad antimicrobial spectrum.

[Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits].

Objective: To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).

Methods: Forty 12-month-old male rabbits with an average of(2.73±0.

Tumor microenvironment-responsive nanohybrid for hypoxia amelioration with photodynamic and near-infrared II photothermal combination therapy.

Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has been widely investigated for tumor treatment. However, the limited tissue penetration depth of light in the near-infrared I (NIR-I) region and the hypoxic tumor microenvironment (TME) severely constrain their clinical applications. To address these challenges, in the present study, we developed a chlorin e6 (Ce6) and MnO-coloaded, hyaluronic acid (HA)-coated single-walled carbon nanohorns (SWNHs) nanohybrid (HA-Ce6-MnO@SWNHs) for PDT and PTT combination therapy of tumor.

Novel metronidazole-derived three-component hybrids as promising broad-spectrum agents to combat oppressive bacterial resistance.

The dreadful bacterial resistance to clinical drugs calls for the development of novel antibacterials. This work developed a class of unique metronidazole-derived three-component hybrids as promising antibacterial therapeutic alternatives. Bioactive assay discovered that p-chlorophenylhydrazone derivative 6b possessed excellent ability to suppress the growth of drug-resistant E.

Discovery of unique thiazolidinone-conjugated coumarins as novel broad spectrum antibacterial agents.

Unique coumarin conjugates with thiazolidinone as novel structural antibacterial modulators were exploited to combat the lethal multidrug-resistant bacterial infections. Bioactivity evaluation identified that indole-incorporated coumarin thiazolidinone conjugate 14a with low cytotoxicity to mammalian cells showed a broad antibacterial spectrum and exerted potent inhibition efficiencies to the tested germs at low concentrations (0.25-2 μg/mL).

Design, synthesis, and insecticidal and fungicidal activities of quaternary ammonium salt derivatives of a triazolyphenyl isoxazoline insecticide.

Background: Insect pests seriously decrease the yield and quality of agricultural crops. Resistance to commonly used insecticides is increasingly undermining their effectiveness, and therefore the development of agents with novel modes of action is desirable. Isoxazolines are a new class of insecticides that act on γ-aminobutyric acid (GABA) gated chloride channels.

An unanticipated discovery towards novel naphthalimide corbelled aminothiazoximes as potential anti-MRSA agents and allosteric modulators for PBP2a.

Available therapeutic strategies are urgently needed to conquer multidrug resistance of MRSA. A visible effort was guided towards the advancement of novel antibacterial framework of naphthalimide corbelled aminothiazoximes, and desired to assert some insight on the conjunction of individual pharmacophore with distinct biological activities and unique action mechanism. Preliminary assessment displayed that dimethylenediamine derivative 13d presented a wonderful inhibition on MRSA (MIC = 0.

Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment.

The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. These compounds showed significant antifungal potency toward some tested fungi.

One-pot synthesis of Ga-doped ultrasmall gold nanoclusters for PET/CT imaging of tumors.

Gold nanoclusters (AuNCs) have attracted much attention for tumor theranostics in recent years because of their ability of renal clearance and to escape the reticuloendothelial system (RES) sequestration. In this study, we presented a novel method to synthesize Ga-doped (labeled) AuNCs by simultaneous reduction of GaCl and HAuCl by glutathione. As synthesized Ga-doped, glutathione-coated AuNCs (Ga-GSH@AuNCs) were ultrasmall in size (<2 nm), highly stable under physiological conditions and renally clearable, and had high efficiency for tumor targeting.

Molecular design and preparation of 2-aminothiazole sulfanilamide oximes as membrane active antibacterial agents for drug resistant Acinetobacter baumannii.

A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line.

Neuroprotective effects of dropping pills in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. dropping pill (GBDP), a unique Chinese leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the extract EGb 761.