Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.

Activation of the Influenza B M2 Proton Channel (BM2).

Influenza B viruses have cocirculated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we performed membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant channel to explore its pH-dependent conformational switch.

Megamolecule Self-Assembly Networks: A Combined Computational and Experimental Design Strategy.

This work describes the use of computational strategies to design megamolecule building blocks for the self-assembly of lattice networks. The megamolecules are prepared by attaching four Cutinase-SnapTag fusion proteins (CS fusions) to a four-armed linker, followed by functionalizing each fusion with a terpyridine linker. This functionality is designed to participate in a metal-mediated self-assembly process to give networks.

Activation of the influenza B M2 proton channel (BM2).

Influenza B viruses have co-circulated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we perform the membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant to explore its pH-dependent conformational switch.

Mechanism of phosphate release from actin filaments.

After ATP-actin monomers assemble filaments, the ATP's [Formula: see text]-phosphate is hydrolyzedwithin seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release.

Text information security protection method based on computer-generated holograms.

Currently, computer-generated holograms (CGHs) based on ray tracing technology are generated faster and faster, and the reconstructed scenes are getting bigger and bigger and contain more and more information. Based on this situation, there are also more applications of using CGHs to hide information, but there is a lack of research on the ability to hide information. To address this issue, this paper proposes a point-sampling CGH method based on ray tracing.

Diseased Erythrocyte Enrichment Based on I-Shaped Pillar DLD Arrays.

Enrichment of erythrocytes is a necessary step in the diagnosis of blood diseases. Due to the high deformability and viscosity of erythrocytes, they cannot be regarded as stable point-like solids, so the influence of their deformability on fluid dynamics must be considered. Therefore, by using the special effect of an I-shaped pillar (I-pillar) on erythrocytes, erythrocytes with different deformability can be made to produce different provisional distances in the chip, so as to achieve the separation of the two kinds of erythrocytes.

Copper-Catalyzed Direct Asymmetric Vinylogous Mannich Reaction between β,γ-Alkynyl-α-ketimino Esters and β,γ-Unsaturated -Acylpyrazoles.

We report a Cu(I)-Ph-BPE-catalyzed asymmetric vinylogous Mannich reaction of β,γ-alkynyl-α-ketimino esters with β,γ-unsaturated -acylpyrazoles. In this process, the Cu(I)-Ph-BPE catalyst activates the β,γ-alkynyl-α-ketimino ester through N,O-coordination, enabling the subsequent nucleophilic addition of a dienolate generated from the β,γ-unsaturated -acylpyrazole via α-position deprotonation with a catalytic amount of tertiary amine. The reactions gave useful products with very high enantioselectivities.

Hyperspectral imaging for non-invasive blood oxygen saturation assessment.

Hyperspectral Imaging (HSI) seamlessly integrates imaging and spectroscopy, capturing both spatial and spectral data concurrently. With widespread applications in medical diagnostics, HSI serves as a noninvasive tool for gaining insights into tissue characteristics. The distinctive spectral profiles of biological tissues set HSI apart from traditional microscopy in enabling in vivo tissue analysis.

-Means Clustering Coarse-Graining (KMC-CG): A Next Generation Methodology for Determining Optimal Coarse-Grained Mappings of Large Biomolecules.

Coarse-grained (CG) molecular dynamics (MD) has become a method of choice for simulating various large scale biomolecular processes; therefore, the systematic definition of the CG mappings for biomolecules remains an important topic. Appropriate CG mappings can significantly enhance the representability of a CG model and improve its ability to capture critical features of large biomolecules. In this work, we present a systematic and more generalized method called -means clustering coarse-graining (KMC-CG), which builds on the earlier approach of essential dynamics coarse-graining (ED-CG).

Ion channels and transporters regulate nutrient absorption in health and disease.

Ion channels and transporters are ubiquitously expressed on cell membrane, which involve in a plethora of physiological process such as contraction, neurotransmission, secretion and so on. Ion channels and transporters is of great importance to maintaining membrane potential homeostasis, which is essential to absorption of nutrients in gastrointestinal tract. Most of nutrients are electrogenic and require ion channels and transporters to absorb.

Mechanism of Phosphate Release from Actin Filaments.

After ATP-actin monomers assemble filaments, the ATP's γ-phosphate is hydrolyzed within seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release.

Supervised Contrastive Learning with Angular Margin for the Detection and Grading of Diabetic Retinopathy.

Many researchers have realized the intelligent medical diagnosis of diabetic retinopathy (DR) from fundus images by using deep learning methods, including supervised contrastive learning (SupCon). However, although SupCon brings label information into the calculation of contrastive learning, it does not distinguish between augmented positives and same-label positives. As a result, we propose the concept of Angular Margin and incorporate it into SupCon to address this issue.

Function of TRP channels in monocytes/macrophages.

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium.

Research Progress on TRPA1 in Diseases.

For a long time, the physiological activity of TRP ion channels and the response to various stimuli have been the focus of attention, and the physiological functions mediated by ion channels have subtle links with the occurrence of various diseases. Our group has been engaged in the study of ion channels. In recent years, the report rate of TRPA1, the only member of the TRPA subfamily in the newly described TRP channel, has been very high.

Alternative stable states in the intestinal ecosystem: proof of concept in a rat model and a perspective of therapeutic implications.

Background: Chronic immune-mediated diseases are rapidly expanding and notoriously difficult to cure. Altered relatively stable intestinal microbiota configurations are associated with several of these diseases, and with a possible pre-disease condition (more susceptible to disease development) of the host-microbiota ecosystem. These observations are reminiscent of the behavior of an ecosystem with alternative stable states (different stable configurations that can exist under identical external conditions), and we recently postulated that health, pre-disease and disease represent such alternative states.

The Gut-Immune-Brain Axis in Autism Spectrum Disorders; A Focus on Amino Acids.

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that affect communication and social behavior. Besides social deficits, systemic inflammation, gastrointestinal immune-related problems, and changes in the gut microbiota composition are characteristic for people with ASD. Animal models showed that these characteristics can induce ASD-associated behavior, suggesting an intimate relationship between the microbiota, gut, immune system and the brain in ASD.

Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.

Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood. Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA . Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).

Hierarchical MoS /Carbon Composite Microspheres as Advanced Anodes for Lithium/Sodium-Ion Batteries.

It is crucial to design advanced electrodes with large Li/Na-ion storage capacities for the development of next-generation battery systems. Herein, hierarchical MoS /C composite microspheres were constructed by facile template-free self-assembly sulfurization plus post-carbonization. Cross-linked MoS nanosheets and outer carbon layer are organically combined together to form composite microspheres with diameters of 400-500 nm.

Serum CD166: A novel biomarker for predicting nasopharyngeal carcinoma response to radiotherapy.

The present study aimed to identify whether CD166 can be used as a biomarker for predicting the response of nasopharyngeal carcinoma (NPC) to radiotherapy. The serum concentration of CD166 in patients with NPC were detected by enzyme-linked immunosorbent assay. The secreted level of CD166 with radioresistant NPC was significantly higher than that with radiosensitive NPC.

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice.

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs.

mTOR plays an important role in cow's milk allergy-associated behavioral and immunological deficits.

Autism spectrum disorder (ASD) is multifactorial, with both genetic as well as environmental factors working in concert to develop the autistic phenotype. Immunological disturbances in autistic individuals have been reported and a role for food allergy has been suggested in ASD. Single gene mutations in mammalian target of rapamycin (mTOR) signaling pathway are associated with the development of ASD and enhanced mTOR signaling plays a central role in directing immune responses towards allergy as well.