Molecular Mechanisms of Reversal of Multidrug Resistance in Breast Cancer by Inhibition of P-gp by Cytisine N-Isoflavones Derivatives Explored Through Network Pharmacology, Molecular Docking, and Molecular Dynamics.

The compound CNI1, identified as a novel antitumor agent based on the cytisine N-isoflavones scaffold, and its series of cytisine N-isoflavones derivatives (CNI2, CNI3, and CNI4), were first isolated from bitter bean seeds, a traditional Chinese medicinal source, by our research team. Cellular activity assays combined with virtual screening targeting P-gp revealed that CNI1, along with the three cytisine N-isoflavones derivatives, CNI2, CNI3, and CNI4, exhibited significant multidrug resistance (MDR) reversal activity in breast cancer. Despite this promising outcome, the precise molecular mechanisms and key targets involved in the MDR reversal of these compounds remain to be elucidated.

Catalyzed Asymmetric Michael Additions of 1-Pyrroline Esters with β-Fluoroalkyl Alkenyl Imides and Azodicarboxylates.

The asymmetric Michael addition reactions of 1-pyrroline esters with β-fluoroalkyl alkenyl imides and dialkyl azodicarboxylates catalyzed by the AgOAc/Ph-phosferrox or CuOAc/(R)-BINAP complex have been developed. A series of chiral 1,5,5-trisubstituted pyrroline ester derivatives have been obtained in 53%-90% yields with 80%-99% ee's and all > 20:1 dr. The gram-scale synthesis and synthetic application of the chiral trifluoromethylated 1-pyrroline adducts were exhibited: the pyrrolizidin-3-one analogue was first synthesized with 94% ee and > 20:1 dr through two steps of hydrolysis and reductive cyclization; the pyrrolidine and lactam derivatives were also successfully provided under the reducing conditions of NaBHCN and Pd/C─H, respectively.

Enhanced electrochemical performance of NHVO in aqueous zinc-ion batteries PVP intercalation and oxygen vacancy engineering.

Polyvinyl pyrrolidone (PVP)-modified NHVO demonstrates superior electrochemical performance (432.3 mA h g at 0.1 A g; 91.

Cascade-amplified Oxidative Stress via Bandgap-Tuned KBiO Perovskite for Cancer Therapy.

Sonodynamic therapy (SDT) is a promising cancer treatment due to its ability to utilize ultrasound (US) to activate sonosensitizers, generating reactive oxygen species (ROS) for tumor suppression. High-valence bismuth, known for its unique photoacoustic properties and biocompatibility, has shown great potential when combined with SDT. However, conventional sonosensitizers with large bandgaps and electron-hole recombination have limited SDT's effectiveness.

Catching CRISPR-Cas9 in Action.

CRISPR-Cas9 has revolutionized genome editing, yet its structural dynamics and functional properties remain incompletely understood, partly due to limited atomic-level characterization of its active conformation with a full R-loop. Capitalizing on recent advances in Cas9 structural determination, we constructed a catalytic-state Cas9 model bound to a R-loop and performed an integrated computational investigation. Our molecular dynamics simulations reveal substantial conformational heterogeneity in the PAM (protospacer-adjacent motif)-distal nontarget DNA strand and adjacent Cas9 regions, leading to dynamically fluctuating interactions, thereby challenging experimental resolution of the full R-loop complex.

Reactive Polymers of Intrinsic Microporous Aerogels for Rapid Mustard Gas Detoxification.

Polymers of intrinsic microporosity (PIMs) have broad application prospects in the detoxification of chemical warfare agents (CWAs) due to their unique pore structure, good tunable reactivity, and solution processability. However, its pore structure is relatively homogeneous, resulting in high resistance to mass transfer. Here, inspired by fractal structure in nature, a structure engineering strategy is proposed to develop 3D reactive nanofibrous aerogels featuring hierarchical porous structures to minimize mass transfer resistance.

Deciphering the Inhibitory Mechanism of ALS-Associated N352S and S352p Variants against TDP-43 Aggregation and Its Destabilization Effect on TDP-43 Protofibrils.

Amyotrophic lateral sclerosis (ALS) is closely related to ubiquitin-positive inclusions formed by transactive response deoxyribonucleic acid (DNA) binding protein of 43 kDa (TDP-43). Previous experiments identified that the ALS-linked familial variant, N352S (asparagine substituted by serine), and subsequent phosphorylation of S352 (S352p) are associated with the aggregation of TDP-43. However, the underlying molecular mechanisms are still not fully understood.

Prediction of Local Drug Exposure of Dry Powder Inhaler CXG87 (budesonide/formoterol) Using Physiologically-Based Pharmacokinetic Model.

Inhaled formulations are the first choices for treating asthma and chronic obstructive pulmonary disease (COPD). Both local and systemic exposures need to be considered when assessing the efficacy and safety of inhaled drugs. Physiologically-based pharmacokinetic (PBPK) models were constructed and verified for budesonide and formoterol with different inhalation devices, CXG87 (test (T) formulation) and Symbicort® Turbuhaler® (reference (R) formulation).

Bardoxolone Derivatives as Novel Pseudo-Natural Necroptosis Inhibitors by Destabilizing HSP90 Client Proteins.

Targeting necroptosis has been confirmed as an efficient treatment strategy for inflammatory diseases. 2-Cyano-3,12-dioxo-olean-1,9-diene-28-carboxylic acid (CDDO) was previously identified as a pseudonatural-product necroptosis inhibitor. However, CDDO was inactive in murine cells and less active in human cells.

Spatiotemporal E-Nose with Laser Tailoring and Chromatography Inspiration.

The study introduces a spatiotemporal chromatography-mimicking (SCM) e-nose that integrates laser-tailored graphene paper with a microchamber for precise volatile organic compound (VOC) discrimination. The SCM e-nose overcomes traditional array limitations with a single multifunctional component capable of accurate VOC differentiation via chromatography-mimic features. Advanced laser-engraving techniques fabricate a gas-permeable interdigitated electrode from graphene paper as the sieving framework.

SpecRecFormer: Deep Learning-Driven Adaptive Component Identification of PAH Mixtures Based on Single-Component Raman Spectra.

The identification of components in mixed spectra is a fundamental challenge in spectral analysis, complicated by factors such as spectral peak overlap due to structural similarities, shifts in characteristic peaks from molecular interactions, and interferences caused by matrix effects. While deep learning offers robust feature extraction capabilities and notable advantages in addressing these challenges, it still faces significant obstacles, including the limited availability of labeled spectral data for effective training and the difficulty of applying fixed-threshold predictive models to spectra containing uncertain components. This paper established a deep learning model, SpecRecFormer, for the rapid identification of individual components in mixed polycyclic aromatic hydrocarbons (PAHs) based on their Raman spectra.

Defect Engineering for Flexible n-Type MoTiCT -MXene Thermoelectric Efficiency Enhancement.

With the rapid advancement of wearable electronics, the demand for efficient portable power supplies has become increasingly urgent. Thermoelectric materials, which can directly convert heat, such as body heat, into electricity, offer a promising avenue for sustainable energy supplementation. However, achieving a high thermoelectric performance in flexible materials suitable for body heat harvesting remains a significant challenge.

Dielectric Constant Estimation of Spherical Particle-Filled Nanocomposites Based on the Poon and Shin Model, Considering Interphase Properties.

A revised version of the Poon and Shin (PS) model, incorporating the effects of the interphase, is introduced to predict the dielectric permittivity of polymer nanocomposites reinforced with spherical nanoparticles. In this modified approach, both the spherical nanoparticle and its surrounding interphase region are treated as an equivalent nanoparticle, modeled as a core-shell structure. This assumption enables a more accurate representation of the composite, where the polymer matrix and the equivalent nanoparticles form a homogeneous mixture.

Efficient degradation of antibiotic pollutants in water by Ca/Ce Co-doped BiOCO photocatalysts.

Aiming at the bottleneck problems of limited visible light response range and high carrier recombination rate of BiOCO (BOC) photocatalyst, Ca/Ce co-doped BiOCO composite photocatalyst was constructed by hydrothermal method. The analysis of different characterization techniques shows that double doping can lead to lattice distortion and induce oxygen defects. Under visible light irradiation, the degradation efficiency of ciprofloxacin (CIP) and levofloxacin (LVX) by BOC-Ca-Ce4 reached 92.

Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3.

One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects.

Electrospinning Trilayer Dressing of PLA/ZnO with Controlled Released Profiles for Visible pH Monitoring and Effective Exudate Management.

To address persistent challenges in wound care, including exudate management, infection prevention, and healing monitoring, this study developed a multifunctional fiber dressing using electrospinning technology. The system integrates a patterned hydrophobic polylactic acid/zinc oxide (PLA/ZnO) inner layer providing antimicrobial protection and exudate drainage; a polyacrylonitrile/polydopamine (PAN/PDA) intermediate water transport layer enabling unidirectional exudate transfer; and an outer PAN-based functional membrane incorporating sodium polyacrylate (SPA), phenol red (PSP), and tetracycline hydrochloride (TCH) for controlled drug release and visual wound status monitoring. The comprehensive evaluation revealed exceptional performance: rapid exudate removal within 3.

Growth of NIR-II-Responsive Gold Nanobipyramids with Improved Yield and a Study of Their Application in Cancer Therapy.

Gold nanobipyramids (Au NBPs), as a novel and emerging plasmonic nanomaterial, have shown larger local electric field enhancements, larger optical cross-sections, and higher refractive index sensitivity compared to other plasmonic nanoparticles. Besides, their localized surface plasmon resonance (LSPR) absorption can be tailored to cover the entire NIR-II light region, which is crucial for clinical cancer treatment. However, strategies to synthesize Au NBPs with an NIR-II light response still have several disadvantages, such as tedious procedures and the use of hazardous chemical substances.

Synergistic hybridization between third-period and fifth-period transition metal orbitals in entropy-stabilized layered double hydroxides for long-term oxygen evolution catalysis.

The development of high-entropy electrocatalysts with optimized activity-stability balance represents a critical advancement in overcoming the efficiency limitations of oxygen evolution reaction (OER) for sustainable hydrogen production. Herein, a rational design of quinary high-entropy layered double hydroxide microspheres comprising synergistic 3d transition metals (Ni, Fe, Co, Mn) and high-valent 5d tungsten (W) is demonstrated through a facile hydrothermal strategy. The optimized NiFeCoMnW exhibits exceptional OER performance in alkaline media, achieving a remarkably low overpotential of 204 mV at 10 mA cm.

Structural isomers of imine-linked covalent organic cages with divergent photocatalytic properties.

The impact of linkage orientation as structural isomers on the properties of covalent organic cages (COCs) has been investigated. Isomeric imine-linked COCs, featuring triphenylamine as the donor and anthracene as the acceptor, TNCA and TCNA, were synthesized and exhibited significant differences in their optoelectronic properties, which in turn affect their photocatalytic performance.

MXene Jacketed Amorphous GaO Nanofibers Modulate the Fiber Surface-Rich Electron for Boosted Electrocatalytic Ammonia Synthesis.

Nitrogen (N) activation and the hydrogen evolution reaction pose significant limitations on the electrocatalytic nitrogen reduction reaction (NRR) performance. The exclusive electronic structure of the main group elements has the advantage of inhibiting hydrogen generation in electrochemical NRR. However, the poor conductivity and activity remain the obstacles to its application.

MMG-Based Motion Segmentation and Recognition of Upper Limb Rehabilitation Using the YOLOv5s-SE.

Mechanomyography (MMG) is a non-invasive technique for assessing muscle activity by measuring mechanical signals, offering high sensitivity and real-time monitoring capabilities, and it has many applications in rehabilitation training. Traditional MMG-based motion recognition relies on feature extraction and classifier training, which require segmenting continuous actions, leading to challenges in real-time performance and segmentation accuracy. Therefore, this paper proposes an innovative method for the real-time segmentation and classification of upper limb rehabilitation actions based on the You Only Look Once (YOLO) algorithm, integrating the Squeeze-and-Excitation (SE) attention mechanism to enhance the model's performance.

YOLO-PEL: The Efficient and Lightweight Vehicle Detection Method Based on YOLO Algorithm.

YOLOv8-PEL shows outstanding performance in detection accuracy, computational efficiency, and generalization capability, making it suitable for real-time and resource-constrained applications. This study aims to address the challenges of vehicle detection in scenarios with fixed camera angles, where precision is often compromised for the sake of cost control and real-time performance, by leveraging the enhanced YOLOv8-PEL model. We have refined the YOLOv8n model by introducing the innovative C2F-PPA module within the feature fusion segment, bolstering the adaptability and integration of features across varying scales.

STING-activable immunomodulatory bio-glue for multiple postsurgical management.

In addition to the robust adhesive properties, there is a pressing demand for ideal adhesives in tumor surgery that possess anti-tumor therapeutic effects. In this study, we introduce BSA-MnO-GP@Ca-Y (BMGY) bio-glue by integrating bovine serum albumin (BSA)-MnO, genipin (GP), and Ca-Y zeolite. Ca-Y zeolite exhibits the thrombin activity for hemostasis, while the cross-linking of BSA, GP, and skin tissue induces wound adherence upon laser irradiation for normalized skin structure within nine days.

modulates mating behavior by ORs and antennae structural genes in the silkworm.

Gene expression is under strict and precise control to regulate organism development and maintain various physiological functions. The Mediator complex is a regulator of gene transcription. Our study focused on , a component of the Mediator complex in the .