Machine learning with active pharmaceutical ingredient/polymer interaction mechanism:Prediction for complex phase behaviors of pharmaceuticals and formulations

The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical formulations.In this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular descriptors.Under the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'screening.The results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.

Electrostatic Interaction-directed Construction of Hierarchical Nanostructured Carbon Composite with Dual Electrical Conductive Networks for Zinc-ion Hybrid Capacitors with Ultrastability

Metal-organic framework(MOF)-derived carbon composites have been considered as the promising materials for energy storage.However,the construction of MOF-based composites with highly controllable mode via the liquid-liquid synthesis method has a great challenge because of the simultaneous heterogeneous nucleation on substrates and the self-nucleation of individual MOF nanocrystals in the liquid phase.Herein,we report a bidirectional electrostatic generated self-assembly strategy to achieve the precisely controlled coatings of single-layer nanoscale MOFs on a range of substrates,including carbon nanotubes(CNTs),graphene oxide(GO),MXene,layered double hydroxides(LDHs),MOFs,and SiO_(2).The obtained MOF-based nanostructured carbon composite exhibits the hierarchical porosity(V_(meso)/V_(micro)∶2.4),ultrahigh N content of 12.4 at.%and"dual electrical conductive networks."The assembled aqueous zinc-ion hybrid capacitor(ZIC)with the prepared nanocarbon composite as a cathode shows a high specific capacitance of 236 F g^(-1)at 0.5 A g^(-1),great rate performance of 98 F g^(-1)at 100 A g^(-1),and especially,an ultralong cycling stability up to 230000 cycles with the capacitance retention of 90.1%.This work develops a repeatable and general method for the controlled construction of MOF coatings on various functional substrates and further fabricates carbon composites for ZICs with ultrastability.

Silica-modified Pt/TiO_(2) catalysts with tunable suppression of strong metal-support interaction for cinnamaldehyde hydrogenation

Tuning Strong Metal-support Interactions(SMSI)is a key strategy to obtain highly active catalysts,but conventional methods usually enable TiO_(x) encapsulation of noble metal components to minimize the exposure of noble metals.This study demonstrates a catalyst preparation method to modulate a weak encapsulation of Pt metal nanoparticles(NPs)with the supported TiO_(2),achieving the moderate suppression of SMSI effects.The introduction of silica inhibits this encapsulation,as reflected in the characterization results such as XPS and HRTEM,while the Ti^(4+) to Ti^(3+) conversion due to SMSI can still be found on the support surface.Furthermore,the hydrogenation of cinnamaldehyde(CAL)as a probe reaction revealed that once this encapsulation behavior was suppressed,the adsorption capacity of the catalyst for small molecules like H_(2) and CO was enhanced,which thereby improved the catalytic activity and facilitated the hydrogenation of CAL.Meanwhile,the introduction of SiO_(2) also changed the surface structure of the catalyst,which inhibited the occurrence of the acetal reaction and improved the conversion efficiency of C=O and C=C hydrogenation.Systematic manipulation of SMSI formation and its consequence on the performance in catalytic hydrogenation reactions are discussed.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Magnetic Interactions with Strain Gradient in Ultrathin Pr_(0.67)Sr_(0.33)MnO_(3) Films

Strain gradient is a normal phenomenon around a heterostructural interface in ultrathin film,and it is important to determine its effect on magnetic interactions to understand interfacial coupling.In this work,ultrathin Pr_(0.67)Sr_(0.33)MnO_(3)(PSMO)films on different substrates are studied.For PSMO film under different in-plane strain conditions,the saturated magnetization and Curie temperature can be qualitatively explained by double-exchange interaction and the Jahn-Teller distortion.However,the difference in the saturated magnetization with zero field cooling and 5 T field cooling is proportional to the strain gradient.Strain-gradient-induced structural disorder is proposed to enhance phonon-electron antiferromagnetic interactions and the corresponding antiferromagnetic-to-ferromagnetic phase transition via a strong magnetic field during the field cooling process.A non-monotonous structural transition of the MnO_(6) octahedral rotation can enlarge the strain gradient in PSMO film on a SrTiO_(3) substrate.This work demonstrates the existence of the flexomagnetic effect in ultrathin manganite film,which should be applicable to other complex oxide systems.

FLOCKING OF A THERMODYNAMIC CUCKER-SMALE MODEL WITH LOCAL VELOCITY INTERACTIONS

In this paper, we study the flocking behavior of a thermodynamic Cucker–Smale model with local velocity interactions. Using the spectral gap of a connected stochastic matrix, together with an elaborate estimate on perturbations of a linearized system, we provide a sufficient framework in terms of initial data and model parameters to guarantee flocking. Moreover, it is shown that the system achieves a consensus at an exponential rate.

Local coordination and electronic interactions of Pd/MXene via dual‐atom codoping with superior durability for efficient electrocatalytic ethanol oxidation

Catalyst design relies heavily on electronic metal‐support interactions,but the metal‐support interface with an uncontrollable electronic or coordination environment makes it challenging.Herein,we outline a promising approach for the rational design of catalysts involving heteroatoms as anchors for Pd nanoparticles for ethanol oxidation reaction(EOR)catalysis.The doped B and N atoms from dimethylamine borane(DB)occupy the position of the Ti_(3)C_(2)lattice to anchor the supported Pd nanoparticles.The electrons transfer from the support to B atoms,and then to the metal Pd to form a stable electronic center.A strong electronic interaction can be produced and the d‐band center can be shifted down,driving Pd into the dominant metallic state and making Pd nanoparticles deposit uniformly on the support.As‐obtained Pd/DB–Ti_(3)C_(2)exhibits superior durability to its counterpart(∼14.6%retention)with 91.1%retention after 2000 cycles,placing it among the top single metal anodic catalysts.Further,in situ Raman and density functional theory computations confirm that Pd/DB–Ti_(3)C_(2)is capable of dehydrogenating ethanol at low reaction energies.

Resistive field generation in intense proton beam interaction with solid targets

The Brown-Preston-Singleton(BPS)stopping power model is added to our previously developed hybrid code to model ion beam-plasma interaction.Hybrid simulations show that both resistive field and ion scattering effects are important for proton beam transport in a solid target,in which they compete with each other.When the target is not completely ionized,the self-generated resistive field effect dominates over the ion scattering effect.However,when the target is completely ionized,this situation is reversed.Moreover,it is found that Ohmic heating is important for higher current densities and materials with high resistivity.The energy fraction deposited as Ohmic heating can be as high as 20%-30%.Typical ion divergences with half-angles of about 5°-10°will modify the proton energy deposition substantially and should be taken into account.

Epicatechin attenuates lead(Pb)-induced cognitive impairment in mice:regulation on Nrf2 signaling pathway,and interference on the interaction between Pb with albumin

Epicatechin(EC)was used in this study to antagonize the cognitive dysfunction caused by lead(Pb)exposure in mice.Eight-week-old male Kunming mice were treated with PbCl_(2)(20 mg/kg)and/or EC(50 mg/kg)by gavage administration for 4 weeks.Morris water maze test showed that EC could improve memory dysfunction induced by Pb.EC antagonized Ca^(2+)overload,activated Nrf2 signaling pathway and reduced the accumulation of Pb in the brain and serum,which suggested that EC might alter Pb distribution in mice.In vitro,spectroscopic analysis,potentiometric titration and docking studies were applied to inquiry into the interaction between bovine serum albumin(BSA)and Pb^(2+)in presence or absence of EC.EC was proved to chelate Pb^(2+)and reduced the interaction between BSA and Pb^(2+).In summary,EC might protect Pb-induced cognitive impairment by activating Nrf2 signaling pathway,and suppressing Pb accumulation via interference on the binding of Pb to albumin.

Generation and regulation of electromagnetic pulses generated by femtosecond lasers interacting with multitargets

Ultrashort and powerful laser interactions with a target generate intense wideband electromagnetic pulses(EMPs).In this study,we report EMPs generated by the interactions between petawatt(30 fs,1.4×10^(20) W/cm^(2))femtosecond(fs)lasers with metal flat,plastic flat,and plastic nanowire-array(NWA)targets.Detailed analyses are conducted on the EMPs in terms of their spatial distribution,time and frequency domains,radiation energy,and protection.The results indicate that EMPs from metal targets exhibit larger amplitudes at varying angles than those generated by other types of targets and are enhanced significantly for NWA targets.Using a plastic target holder and increasing the laser focal spot can significantly decrease the radiation energy of the EMPs.Moreover,the composite shielding materials indicate an effective shielding effect against EMPs.The simulation results show that the NWA targets exert a collimating effect on thermal electrons,which directly affects the distribution of EMPs.This study provides guidance for regulating EMPs by controlling the laser focal spot,target parameters,and target rod material and is beneficial for electromagnetic-shielding design.

The DUF579 proteins GhIRX15s regulate cotton fiber development by interacting with proteins involved in xylan synthesis

Cotton provides the most abundant natural fiber for the textile industry.The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and lignin.To dissect the roles of hemicellulosic polysaccharides during fiber development,four IRREGULAR XYLEM 15(IRX15)genes,GhIRX15-1/-2/-3/-4,were functionally characterized in cotton.These genes encode DUF579 domain-containing proteins,which are homologs of AtIRX15 involved in xylan biosynthesis.The four GhIRX15 genes were predominantly expressed during fiber secondary wall thickening,and the encoded proteins were localized to the Golgi apparatus.Each GhIRX15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double mutant.Silencing of GhIRX15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild type.Intriguingly,GhIRX15-2 and GhIRX15-4 formed homodimers and heterodimers.In addition,the GhIRX15s showed physical interaction with glycosyltransferases GhGT43C,GhGT47A and GhGT47B,which are responsible for synthesis of the xylan backbone and reducing end sequence.Moreover,the GhIRX15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis,such as GhGUX1/2,GhGXM1/2 and GhTBL1.These findings suggest that GhIRX15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes.

Dynamic interactive bitwise meta-holography with ultra-high computational and display frame rates

Interactive holography offers unmatched levels of immersion and user engagement in the field of future display.Despite of the substantial progress has been made in dynamic meta-holography,the realization of real-time,highly smooth interactive holography remains a significant challenge due to the computational and display frame rate limitations.In this study,we introduced a dynamic interactive bitwise meta-holography with ultra-high computational and display frame rates.To our knowledge,this is the first reported practical dynamic interactive metasurface holographic system.We spa-tially divided the metasurface device into multiple distinct channels,each projecting a reconstructed sub-pattern.The switching states of these channels were mapped to bitwise operations on a set of bit values,which avoids complex holo-gram computations,enabling an ultra-high computational frame rate.Our approach achieves a computational frame rate of 800 kHz and a display frame rate of 23 kHz on a low-power Raspberry Pi computational platform.According to this methodology,we demonstrated an interactive dynamic holographic Tetris game system that allows interactive gameplay,color display,and on-the-fly hologram creation.Our technology presents an inspiration for advanced dynamic meta-holography,which is promising for a broad range of applications including advanced human-computer interaction,real-time 3D visualization,and next-generation virtual and augmented reality systems.

Confined cobalt single-atom catalysts with strong electronic metal-support interactions based on a biomimetic self-assembly strategy

Designing high-performance and low-cost electrocatalysts for oxygen evolu-tion reaction(OER)is critical for the conversion and storage of sustainable energy technologies.Inspired by the biomineralization process,we utilized the phosphorylation sites of collagen molecules to combine with cobalt-based mononuclear precursors at the molecular level and built a three-dimensional(3D)porous hierarchical material through a bottom-up biomimetic self-assembly strategy to obtain single-atom catalysts confined on carbonized biomimetic self-assembled carriers(Co SACs/cBSC)after subsequent high-temperature annealing.In this strategy,the biomolecule improved the anchoring efficiency of the metal precursor through precise functional groups;meanwhile,the binding-then-assembling strategy also effectively suppressed the nonspecific adsorption of metal ions,ultimately preventing atomic agglomeration and achieving strong electronic metal-support interactions(EMSIs).Experimental characterizations confirm that binding forms between cobalt metal and carbonized self-assembled substrate(Co–O_(4)–P).Theoretical calculations disclose that the local environment changes significantly tailored the Co d-band center,and optimized the binding energy of oxygenated intermediates and the energy barrier of oxygen release.As a result,the obtained Co SACs/cBSC catalyst can achieve remarkable OER activity and 24 h durability in 1 M KOH(η10 at 288 mV;Tafel slope of 44 mV dec-1),better than other transition metal-based catalysts and commercial IrO_(2).Overall,we presented a self-assembly strategy to prepare transition metal SACs with strong EMSIs,providing a new avenue for the preparation of efficient catalysts with fine atomic structures.

Model of self-generated magnetic field generation from relativistic laser interaction with solid targets

Generation of self-generated annular magnetic fields at the rear side of a solid target driven by relativistic laser pulse is investigated by using theoretical analysis and particle-in-cell simulations.The spatial strength distribution of magnetic fields can be accurately predicted by calculating the net flow caused by the superposition of source flow and return flow of hot electrons.The theoretical model established shows good agreement with the simulation results,indicating that the magnetic-field strength scales positively to the temperature of hot electrons.This provides us a way to improve the magnetic-field generation by using a micro-structured plasma grating in front of the solid target.Compared with that for a common flat target,hot electrons can be effectively heated with the well-designed grating size,leading to a stronger magnetic field.The spatial distribution of magnetic fields can be modulated by optimizing the grating period and height as well as the incident angle of the laser pulse.

Enhancing ChatGPT’s Querying Capability with Voice-Based Interaction and CNN-Based Impair Vision Detection Model

This paper presents an innovative approach to enhance the querying capability of ChatGPT,a conversational artificial intelligence model,by incorporating voice-based interaction and a convolutional neural network(CNN)-based impaired vision detection model.The proposed system aims to improve user experience and accessibility by allowing users to interact with ChatGPT using voice commands.Additionally,a CNN-based model is employed to detect impairments in user vision,enabling the system to adapt its responses and provide appropriate assistance.This research tackles head-on the challenges of user experience and inclusivity in artificial intelligence(AI).It underscores our commitment to overcoming these obstacles,making ChatGPT more accessible and valuable for a broader audience.The integration of voice-based interaction and impaired vision detection represents a novel approach to conversational AI.Notably,this innovation transcends novelty;it carries the potential to profoundly impact the lives of users,particularly those with visual impairments.The modular approach to system design ensures adaptability and scalability,critical for the practical implementation of these advancements.Crucially,the solution places the user at its core.Customizing responses for those with visual impairments demonstrates AI’s potential to not only understand but also accommodate individual needs and preferences.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Chemical simulation teaching system based on virtual reality and gesture interaction

Background Most existing chemical experiment teaching systems lack solid immersive experiences,making it difficult to engage students.To address these challenges,we propose a chemical simulation teaching system based on virtual reality and gesture interaction.Methods The parameters of the models were obtained through actual investigation,whereby Blender and 3DS MAX were used to model and import these parameters into a physics engine.By establishing an interface for the physics engine,gesture interaction hardware,and virtual reality(VR)helmet,a highly realistic chemical experiment environment was created.Using code script logic,particle systems,as well as other systems,chemical phenomena were simulated.Furthermore,we created an online teaching platform using streaming media and databases to address the problems of distance teaching.Results The proposed system was evaluated against two mainstream products in the market.In the experiments,the proposed system outperformed the other products in terms of fidelity and practicality.Conclusions The proposed system which offers realistic simulations and practicability,can help improve the high school chemistry experimental education.

Development of Extraction and Detection Method for a Chemotherapeutic Drug with Phenytoin in Biological Samples

Dexamethasone is classified as a corticosteroid and is commonly used among cancer patients to decrease the amount of swelling around the tumor. Among patients with cancer, in particular brain tumors, seizures can become a daily routine in their everyday lives. To counteract the seizures, an antiepileptic drug such as phenytoin is administered to act as an anticonvulsant. Phenytoin and dexamethasone are frequently administrated concurrently to brain cancer patients. A previous study has shown that phenytoin serum concentration decreases when administrated concurrently with dexamethasone. Thus, it is important to monitor the concentration of these two drugs in biological samples to ensure that the proper dosages are administrated to the patients. This study aims to develop an effective extraction and detection method for dexamethasone and phenytoin. A reverse-phase high-performance liquid chromatography (HPLC) method with UV/Vis detection has been developed to separate phenytoin and dexamethasone at 219 nm and 241 nm respectively from urine samples. The mobile phase consists of a mixture of 0.01 M KH2PO4, acetonitrile, and methanol adjusted to pH 5.6 (48:32:20) and is pumped at a flow rate of 1.0 mL/min. Calibration curves were prepared for phenytoin and dexamethasone (r2 > 0.99). An efficient solid-phase extraction (SPE) method for the extraction of dexamethasone and phenytoin from urine samples was developed with the use of C-18 cartridges. The percent recovery for phenytoin and dexamethasone is 95.4% (RSD = 1.15%) and 81.1% (RSD = 3.56%) respectively.

Control of light-matter interactions in two-dimensional materials with nanoparticle-on-mirror structures

Light–matter interactions in two-dimensional(2D)materials have been the focus of research since the discovery of graphene.The light–matter interaction length in 2D materials is,however,much shorter than that in bulk materials owing to the atomic nature of 2D materials.Plasmonic nanostructures are usually integrated with 2D materials to enhance the light–matter interactions,offering great opportunities for both fundamental research and technological applications.Nanoparticle-on-mirror(NPo M)structures with extremely confined optical fields are highly desired in this aspect.In addition,2D materials provide a good platform for the study of plasmonic fields with subnanometer resolution and quantum plasmonics down to the characteristic length scale of a single atom.A focused and up-to-date review article is highly desired for a timely summary of the progress in this rapidly growing field and to encourage more research efforts in this direction.In this review,we will first introduce the basic concepts of plasmonic modes in NPo M structures.Interactions between plasmons and quasi-particles in 2D materials,e.g.,excitons and phonons,from weak to strong coupling and potential applications will then be described in detail.Related phenomena in subnanometer metallic gaps separated by 2D materials,such as quantum tunneling,will also be touched.We will finally discuss phenomena and physical processes that have not been understood clearly and provide an outlook for future research.We believe that the hybrid systems of2D materials and NPo M structures will be a promising research field in the future.

Docking of Human Band 3 Anion Transporter Proteins with Their Plasmodium falciparum Interactors Based on Short Linear Motifs

Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.