Insights into the chirality-dependent recognition of Danshensu Bingpian Zhi stereoisomers with PPAR.

Peroxisome proliferator-activated receptor γ (PPAR), a nuclear receptor involved in metabolic processes, inflammation, and energy balance, represents a promising therapeutic target for cardiovascular diseases. Danshensu Bingpian Zhi (DBZ), a chiral compound derived from traditional Chinese medicine, exhibits potential as a PPAR agonist. Using an ensemble-based docking approach, molecular dynamics (MD) simulations, and the molecular mechanics generalized born surface area (MM/GBSA) methods, we explored the binding modes and energetics of DBZ stereoisomers with the PPAR ligand-binding domain (LBD).

Four Parallel Pathways in T4 Ligase-Catalyzed Repair of Nicked DNA with Diverse Bending Angles.

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase-AMP complex and the ligase-AMP-DNA complex can have four conformations.

Reversible single-crystal to single-crystal transformation between triangular single-molecule toroics.

We report a method for synthesizing single-molecule magnets through a single-crystal to single-crystal transformation. This process yields two single-molecule magnets with similar triangular Dy cores but distinct solvents and space groups achieved solvent exchange. Magnetic properties reveal that both Dy molecules exhibit similar toroidal moments but manifest diverse multiple magnetization dynamic behaviors owing to the spin-lattice coupling influence from different solvent molecules.

Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study.

Current structural and functional investigations of cholesteryl ester transfer protein (CETP) inhibitor design are nearly entirely based on a fully active mutation (CETP) constructed for protein crystallization, limiting the study of the dynamic structural features of authentic CETP involved in lipid transport under physiological conditions. In this study, we conducted comprehensive molecular dynamics (MD) simulations of both authentic CETP (CETP) and CETP. Considering the structural differences between the N- and C-terminal domains of CETP and CETP, and their crucial roles in lipid transfer, we identified the two domains as binding pockets of the ligands for virtual screening to discover potential lead compounds targeting CETP.

Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently posed a serious threat to global public health. Harringtonine (HT), as a small-molecule antagonist, has antiviral activity against a variety of viruses. There is evidence that HT can inhibit the SARS-CoV-2 entry into host cells by blocking the Spike protein and transmembrane protease serine 2 (TMPRSS2).

Identification of Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents.

High-Throughput Screening for the Potential Inhibitors of SARS-CoV-2 with Essential Dynamic Behavior.

Global health security has been challenged by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Due to the lengthy process of generating vaccinations, it is vital to reposition currently available drugs in order to relieve anti-epidemic tensions and accelerate the development of therapies for Coronavirus Disease 2019 (COVID-19), the public threat caused by SARS-CoV-2. High throughput screening techniques have established their roles in the evaluation of already available medications and the search for novel potential agents with desirable chemical space and more cost-effectiveness.

Efficient inactivation of the contamination with pathogenic microorganisms by a combination of water spray and plasma-activated air.

The global pandemic caused by SARS-CoV-2 has lasted two and a half years and the infections caused by the viral contamination are still occurring. Developing efficient disinfection technology is crucial for the current epidemic or infectious diseases caused by other pathogenic microorganisms. Gas plasma can efficiently inactivate different microorganisms, therefore, in this study, a combination of water spray and plasma-activated air was established for the disinfection of pathogenic microorganisms.

MIL-101(CuFe) Nanozymes with Excellent Peroxidase-like Activity for Simple, Accurate, and Visual Naked-Eye Detection of SARS-CoV-2.

The COVID-19 pandemic has spread to every corner of the world and seriously affected our health and daily activities in the past three years; thereby, it is still urgent to develop various simple, quick, and accurate methods for early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nanozymes, a kind of nanomaterial with intrinsic enzyme-mimicking activity, have emerged as a suitable alternative for both therapy and diagnosis of SARS-CoV-2. Here, ultrasensitive and ultrafast MIL-101(CuFe)-CD147 biosensors are established for the detection of SARS-CoV-2 by a simple colorimetric method.

Electrically controllable self-assembly of gold nanorods into a plasmonic nanostructure for highly efficiency SERS.

In this Letter, a method for the rapid and efficient preparation of ultrasensitive detection substrates by assembling gold nanorod suspensions with the application of an alternating current (AC) field is proposed, and it is found that frequency and voltage are the effective means of regulation. A sandwich structure (parallel SiO plate) not only effectively slows down the evaporation rate, but also visually reveals the changes in the assembly process. Under the optimal assembly conditions, the sensitivity and uniformity of the substrate to different probe molecules are tested.

Markov State Models Underlying the N-Terminal Premodel of TOPK/PBK.

Lymphokine-activated killer T-cell-originated protein kinase (TOPK) is a potential target for cancer therapy. To explore the micromechanism, we proposed the N-terminal premodel (NTPM) of the TOPK monomer via homology modeling and molecular dynamic simulations and analyzed the conformational dynamics by Markov state model analysis. The electronegative insert (ENI) motif of the NTPM can be opened with a small probability under wild type, regulated by the so-called "N-C" interaction zone consisting of the N-terminal head, the coil between β-strand and αC-helix, and the ENI motif.

All-in-One Theranostic Platforms: Deep-Red AIE Nanocrystals to Target Dual-Organelles for Efficient Photodynamic Therapy.

Aggregation-induced emission (AIE) nanoparticles have been widely applied in photodynamic therapy (PDT) over the past few years. However, amorphous nanoaggregates usually occur in their preparation, resulting in loose packing with disordered molecular structures. This still allows free intramolecular motions, thus leading to limited brightness and PDT efficiency.

Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox‑LDL‑induced THP‑1 monocytes.

Numerous studies have shown that the formation of foam cells is of vital importance in the process of atherosclerosis. The aim of the present study was to assess the effects of metformin on foam cell formation in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells and explore its associated mechanism of action. Human monocytic THP-1 cells were pretreated with metformin for 2 h and subsequently treated with ox-LDL for 24 h.

Land-use transition and its driving forces in a minority mountainous area: a case study from Mao County, Sichuan Province, China.

Land-use change is an important research topic in global environmental change. Analyzing land-use change and its driving factors can aid in the evaluation of the current and the determination of future land-use policies. This study took Mao County, Southwest China, as the study area and used the land-use change and statistical data surveyed in 2009 and 2019.

Organelle Interaction and Drug Discovery: Towards Correlative Nanoscopy and Molecular Dynamics Simulation.

The inter-organelle interactions, including the cytomembrane, endoplasmic reticulum, mitochondrion, lysosome, dictyosome, and nucleus, play the important roles in maintaining the normal function and homeostasis of cells. Organelle dysfunction can lead to a range of diseases (e.g.

Accounting Conformational Dynamics into Structural Modeling Reflected by Cryo-EM with Deep Learning.

With the continuous development of structural biology, the requirement for accurate threedimensional structures during functional modulation of biological macromolecules is increasing. Therefore, determining the dynamic structures of bio-macromolecular at high resolution has been a highpriority task. With the development of cryo-electron microscopy (cryo-EM) techniques, the flexible structures of biomacromolecules at the atomic resolution level grow rapidly.

Prediction of low Apgar score at five minutes following labor induction intervention in vaginal deliveries: machine learning approach for imbalanced data at a tertiary hospital in North Tanzania.

Background: Prediction of low Apgar score for vaginal deliveries following labor induction intervention is critical for improving neonatal health outcomes. We set out to investigate important attributes and train popular machine learning (ML) algorithms to correctly classify neonates with a low Apgar scores from an imbalanced learning perspective.

Methods: We analyzed 7716 induced vaginal deliveries from the electronic birth registry of the Kilimanjaro Christian Medical Centre (KCMC).

Sequence Matching between Hemagglutinin and Neuraminidase through Sequence Analysis Using Machine Learning.

To date, many experiments have revealed that the functional balance between hemagglutinin (HA) and neuraminidase (NA) plays a crucial role in viral mobility, production, and transmission. However, whether and how HA and NA maintain balance at the sequence level needs further investigation. Here, we applied principal component analysis and hierarchical clustering analysis on thousands of HA and NA sequences of A/H1N1 and A/H3N2.

Facilely prepared aggregation-induced emission (AIE) nanocrystals with deep-red emission for super-resolution imaging.

Organic nanocrystals (NCs) with high brightness are highly desirable for biological imaging. However, the preparation of NCs by a facile and fast method is still challenging. Herein, an aggregation-induced emission (AIE) luminogen of 4,4'-(5,6-difluorobenzo[][1,2,5]thiadiazole-4,7-diyl)bis(,-bis(4-methoxyphenyl)aniline) (DTPA-BT-F) in the deep-red region is designed with intensive crystalline features to obtain NCs by kinetically controlled nanoprecipitation.

Computational Simulation of HIV Protease Inhibitors to the Main Protease (Mpro) of SARS-CoV-2: Implications for COVID-19 Drugs Design.

SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro.

Molecular Insights into the Recruiting Between UCP2 and DDX5/UBAP2L in the Metabolic Plasticity of Non-Small-Cell Lung Cancer.

Mitochondrial uncoupling protein 2 (UCP2) is distributed in tumor cells with a link to the support of systemic metabolic deregulation, and the downregulation of UCP2 has been unveiled as a biomarker of oncogenesis and chemoresistance in non-small-cell lung cancer (NSCLC) cells. However, the underlying mechanism of how UCP2 cooperates with other proteins in this metabolic reprogramming remains largely unsolved. We employed a combined computational and experimental strategy to explore into the recruiting of DDX5 with other proteins, and we unraveled the underlying structural mechanisms.

Molecular insights into the binding variance of the SARS-CoV-2 spike with human, cat and dog ACE2 proteins.

SARS-CoV-2 has recently caused an epidemic in humans and poses a huge threat to global public health. As a primary receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) exists in different hosts that are in close contact with humans, especially cats and dogs. However, the underlying mechanism of how the spike receptor binding domain (RBD) of SARS-CoV-2 cooperates with human ACE2 (hACE2), cat ACE2 (cACE2) and dog ACE2 (dACE2) and the variation in binding remains largely unsolved.

High Performance NbMoTa-AlO Multilayer Composite Structure Manufacturing by Laser Directed Energy Deposition.

The conventional method of preparing metal-ceramic composite structures causes delamination and cracking defects due to differences in the composite structures' properties, such as the coefficient of thermal expansion between metal and ceramic materials. Laser-directed energy deposition (LDED) technology has a unique advantage in that the composition of the materials can be changed during the forming process. This technique can overcome existing problems by forming composite structures.