The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.

The p53, often referred to as the "guardian of the genome", is a well-established tumor-suppressor protein that plays a critical role in regulating the cell cycle, DNA repair, differentiation, and apoptosis, with its activity primarily modulated by the MDM2 protein (murine double minute 2, also known as HDM2 in humans). Disrupting the protein-protein interaction between p53 and MDM2 represents a promising therapeutic strategy for developing anticancer agents. Recent studies have shown that several spirooxindole-containing compounds exhibit significant antitumor properties, primarily by inhibiting the p53-MDM2 interaction.

Selective Degradation of TEADs by a PROTAC Molecule Exhibited Robust Anticancer Efficacy In Vitro and In Vivo.

Genetic mutations in components of the Hippo pathway frequently lead to the aberrant activation of TEADs, which is often associated with cancer. Consequently, TEADs have been actively pursued as therapeutic targets for diseases driven by TEAD overactivation. In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders.

Physical Adsorption and Raman Spectra of Hydrazine Hydrate on the Graphene Surface.

In experimental studies, hydrazine hydrate is widely employed as a reducing agent for the conversion of graphene oxide to graphene. Herein, we conducted theoretical calculations using cluster models to investigate the adsorption behavior of hydrazine hydrate on the surface of graphene. The calculated adsorption energy reveals that hydrazine hydrate can physically bind to the graphene surface.

Two-Dimensional Rare-Earth-Based Half-Metals with Topological Bimerons.

Two-dimensional magnets with spontaneous topological spin textures have important application prospects in highly integrated spintronic devices. However, so far, the predicted two-dimensional magnets with topological spin textures are mainly based on transition metals, and most of them are semiconductors or metals. Here, based on first-principles calculations, we predict two-dimensional rare-earth-based half-metallic monolayer GdAN (A = Ge, Sn), with 100% spin polarization.

Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy.

Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups.

Engineering the microenvironment of P450s to enhance the production of diterpenoids in .

Cytochrome P450 enzymes play a crucial role as catalysts in the biosynthesis of numerous plant natural products (PNPs). Enhancing the catalytic activity of P450s in host microorganisms is essential for the efficient production of PNPs through synthetic biology. In this study, we engineered to optimize the microenvironment for boosting the activities of P450s, including coexpression with the redox partner genes, enhancing NADPH supply, expanding the endoplasmic reticulum (ER), strengthening heme biosynthesis, and regulating iron uptake.

Bionic Optimization Design and Fatigue Life Prediction of a Honeycomb-Structured Wheel Hub.

The wheel hub is an important component of the wheel, and a good hub design can significantly improve vehicle handling, stability, and braking performance, ensuring safe driving. This article optimized the hub structure through morphological aspects, where reducing the hub weight contributed to enhanced fuel efficiency and overall vehicle performance. By referencing honeycombed structures, a bionic hub design is numerically simulated using finite element analysis and response surface optimization.

IGF2BP3 regulates macrophage-induced inflammation and liver damage in acute-on-chronic liver failure via the RORα-NF-κB signaling axis.

Acute-on-chronic liver failure (ACLF) is a severe condition characterized by high mortality rates, and macrophage-mediated inflammation plays a critical role in its progression. Our previous research has indicated the involvement of the RNA-binding protein IGF2BP3 in the pathogenesis of ACLF. However, the underlying molecular mechanisms contributing to this damage require further elucidation.

Signatures of hybridization of multiple Majorana zero modes in a vortex.

Majorana zero modes (MZMs) are emergent zero-energy topological quasiparticles that are their own antiparticles. Detected MZMs are spatially separated and electrically neutral, so producing hybridization between MZMs is extremely challenging in superconductors. Here, we report the magnetic field response of vortex bound states in superconducting topological crystalline insulator SnTe (001) films.

Efficacy and Safety of Minimally Invasive Neuroendoscopic Surgery in the Therapy of Supratentorial Hypertensive Intracerebral Hemorrhage: A Meta-Analysis.

Objective: To systematically investigate the therapeutic effects of neuroendoscopic (NE) surgery in supratentorial hypertensive intracerebral hemorrhage (HICH), including key indicators such as hematoma evacuation rate, complications, and neurological prognosis, thus comprehensively understanding the superiority of NE surgery in supratentorial HICH therapy, and to provide scientific basis and decision-making support for clinical practice.

Methods: The PubMed, EMBASE, Cochrane, Google, and CNKI databases were searched for relevant literature related to NE surgery for supratentorial HICH published before October 2023. Summary analyses of hematoma evacuation rate, mortality, clinical treatment, good functional outcome (Glasgow Outcome Scale, Glasgow Coma Scale, and modified Rankin Scale), and postoperative complications in the NE group were performed, and Revman 5.

Insights from Ab Initio Molecular Dynamics on the Interface Reaction between Electrolyte and LiMnO Cathode during the Charging Process.

The complex interface reactions are crucial to the performance of the LiMnO cathode material. Here, the interface reactions between the liquid electrolyte and the typical surfaces of LiMnO during the charging process are systematically investigated by ab initio molecular dynamics (AIMD) simulation and first-principles calculation. The results indicate that these interface reactions lead to the formation of hydroxide radicals, oxygen, carbon dioxide, carbonate radicals, and other products, which are consistent with the experimental findings.

Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast.

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories.

Discovery of a Covalent Inhibitor That Overcame Resistance to Venetoclax in AML Cells Overexpressing BFL-1.

Clinical and biological studies have shown that overexpression of BFL-1 is one contributing factor to venetoclax resistance. The resistance might be overcome by a potent BFL-1 inhibitor, but such an inhibitor is rare. In this study, we show that featuring an acrylamide moiety, inhibited the BFL-1/BID interaction with a value of 105 nM.

Development of a novel PCV2 and PCV3 vaccine using virus-like vesicles incorporating Venezuelan equine encephalomyelitis virus-containing vesicular stomatitis virus glycoprotein.

Porcine circovirus disease (PCV) causes substantial economic losses in the pig industry, primarily from porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3). Novel vaccines are necessary to prevent and control PCV infections. PCV coat proteins are crucial for eliciting immunogenic proteins that induce the production of antibodies and immune responses.

Enormous and Tunable Bulk Charge/Spin Photovoltaic Effect in Piezoelectric Binary Materials T-IV-VI and T-V-V.

Understanding the nonlinear response of light and materials is crucial for fundamental physics and next-generation electronic devices. In this work, we have investigated the second-order nonlinear bulk photovoltaic (BPV) and bulk spin photovoltaic (BSPV) effects in the piezoelectric binary materials T-IV-VI and T-V-V (IV = Ge, Sn; VI = S, Se; and V = P, As, Sb, Bi). The independent nonzero conductivity tensors of charge current are derived for these binaries through the symmetry analysis, along with the mechanism for generating pure spin current.

The stability of CsPb(BrCl) all-inorganic mixed halide perovskites.

The use of mixed halide perovskites in the preparation of blue light-emitting diodes (LEDs) is considered to be the most effective and direct approach. However, the introduction of chlorine (Cl) element might raise stability issues in the system and lead to low efficiency, thereby impeding the development of deep blue light-emitting diodes with high efficiency and stability. Determining the alloy concentration and the atomic distribution of bromine-chlorine (Br-Cl) mixed systems is essential for further application of deep blue light-emitting diodes.

Extraction and analysis of high-quality chloroplast DNA with reduced nuclear DNA for medicinal plants.

Background: Obtaining high-quality chloroplast genome sequences requires chloroplast DNA (cpDNA) samples that meet the sequencing requirements. The quality of extracted cpDNA directly impacts the efficiency and accuracy of sequencing analysis. Currently, there are no reported methods for extracting cpDNA from Erigeron breviscapus.

Isolation, identification, and proteomic analysis of outer membrane vesicles of Riemerella anatipestifer SX-1.

Riemerella anatipestifer, belonging to Weeksellaceae family Riemerella, is a bacterium that can infect ducks, geese, and turkeys, causing diseases known as duck infectious serositis, new duck disease, and duck septicemia. We collected diseased materials from ducks on a duck farm in China and then isolated and purified a strain of serotype 1 R. anatipestifer named SX-1.