Novel umami peptides from two Termitomyces mushrooms and molecular docking to the taste receptor T1R1/T1R3

Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.

Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits.In brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli.Once the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular debris.The crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier permeability.In this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development.This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

Analysis of CH_(4) and H_(2) Adsorption on Heterogeneous Shale Surfaces Using aMolecular Dynamics Approach

Determining the adsorption of shale gas on complex surfaces remains a challenge in molecular simulation studies.Difficulties essentially stem from the need to create a realistic shale structure model in terms of mineral heterogeneityand multiplicity.Moreover,precise characterization of the competitive adsorption of hydrogen andmethane in shale generally requires the experimental determination of the related adsorptive capacity.In thisstudy,the adsorption of adsorbates,methane(CH_(4)),and hydrogen(H_(2))on heterogeneous shale surface modelsof Kaolinite,Orthoclase,Muscovite,Mica,C_(60),and Butane has been simulated in the frame of a moleculardynamic’s numerical technique.The results show that these behaviors are influenced by pressure and potentialenergy.On increasing the pressure from 500 to 2000 psi,the sorption effect for CH_(4)significantly increasesbut shows a decline at a certain stage(if compared to H_(2)).The research findings also indicate that raw shalehas a higher capacity to adsorb CH_(4)compared to hydrogen.However,in shale,this difference is negligible.

Facile synthesis of Cu-doped manganese oxide octahedral molecular sieve for the efficient degradation of sulfamethoxazole via peroxymonosulfate activation

Advanced processes for peroxymonosulfate(PMS)-based oxidation are efficient in eliminating toxic and refractory organic pol-lutants from sewage.The activation of electron-withdrawing HSO_(5)^(-)releases reactive species,including sulfate radical(·SO_(4)^(-)),hydroxyl radical(·OH),superoxide radical(·O_(2)^(-)),and singlet oxygen(1O_(2)),which can induce the degradation of organic contaminants.In this work,we synthesized a variety of M-OMS-2 nanorods(M=Co,Ni,Cu,Fe)by doping Co^(2+),Ni^(2+),Cu^(2+),or Fe^(3+)into manganese oxide oc-tahedral molecular sieve(OMS-2)to efficiently remove sulfamethoxazole(SMX)via PMS activation.The catalytic performance of M-OMS-2 in SMX elimination via PMS activation was assessed.The nanorods obtained in decreasing order of SMX removal rate were Cu-OMS-2(96.40%),Co-OMS-2(88.00%),Ni-OMS-2(87.20%),Fe-OMS-2(35.00%),and OMS-2(33.50%).Then,the kinetics and struc-ture-activity relationship of the M-OMS-2 nanorods during the elimination of SMX were investigated.The feasible mechanism underly-ing SMX degradation by the Cu-OMS-2/PMS system was further investigated with a quenching experiment,high-resolution mass spec-troscopy,and electron paramagnetic resonance.Results showed that SMX degradation efficiency was enhanced in seawater and tap water,demonstrating the potential application of Cu-OMS-2/PMS system in sewage treatment.

Exploring the taste presentation and receptor perception mechanism of salty peptides from Stropharia rugosoannulata based on molecular dynamics and thermodynamics simulation

The taste presentation and receptor perception mechanism of the salty peptide of Stropharia rugosoannulata were predicted and verified using peptide omics and molecular interaction techniques.The combination of aspartic acid(D)and glutamic acid(E),or peptide fragments composed of arginine(R),constitute the characteristic taste structural basis of salty peptides of S.rugosoannulata.The taste intensity of the salty peptide positively correlates with its concentration within a specific concentration range(0.25–1.0 mg/mL).The receptor more easily recognizes the first amino acid residue at the N-terminal of salty peptides and the aspartic acid residue in the peptides.GLU513,ASP707,and VAL508 are the critical amino acid residues for the receptor to recognize salty peptides.TRPV1 is specifically the receptor for recognizing salty peptides.Hydrogen bonds and electrostatic interactions are the main driving forces for the interactions between salty peptides and TRPV1 receptors.KSWDDFFTR has the most potent binding capacity with the receptor and has tremendous potential for application in sodium salt substitution.This study confirmed the taste receptor that specifically recognizes salty peptides,analyzed the receptor-peptide binding interaction,and provided a new idea for understanding the taste receptor perception of salty peptides.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Development of in situ characterization techniques in molecular beam epitaxy

Ex situ characterization techniques in molecular beam epitaxy(MBE)have inherent limitations,such as being prone to sample contamination and unstable surfaces during sample transfer from the MBE chamber.In recent years,the need for improved accuracy and reliability in measurement has driven the increasing adoption of in situ characterization techniques.These techniques,such as reflection high-energy electron diffraction,scanning tunneling microscopy,and X-ray photoelectron spectroscopy,allow direct observation of film growth processes in real time without exposing the sample to air,hence offering insights into the growth mechanisms of epitaxial films with controlled properties.By combining multiple in situ characterization techniques with MBE,researchers can better understand film growth processes,realizing novel materials with customized properties and extensive applications.This review aims to overview the benefits and achievements of in situ characterization techniques in MBE and their applications for material science research.In addition,through further analysis of these techniques regarding their challenges and potential solutions,particularly highlighting the assistance of machine learning to correlate in situ characterization with other material information,we hope to provide a guideline for future efforts in the development of novel monitoring and control schemes for MBE growth processes with improved material properties.

Recent developments in selective laser processes for wearable devices

Recently,the increasing interest in wearable technology for personal healthcare and smart virtual/augmented reality applications has led to the development of facile fabrication methods.Lasers have long been used to develop original solutions to such challenging technological problems due to their remote,sterile,rapid,and site-selective processing of materials.In this review,recent developments in relevant laser processes are summarized under two separate categories.First,transformative approaches,such as for laser-induced graphene,are introduced.In addition to design optimization and the alteration of a native substrate,the latest advances under a transformative approach now enable more complex material compositions and multilayer device configurations through the simultaneous transformation of heterogeneous precursors,or the sequential addition of functional layers coupled with other electronic elements.In addition,the more conventional laser techniques,such as ablation,sintering,and synthesis,can still be used to enhance the functionality of an entire system through the expansion of applicable materials and the adoption of new mechanisms.Later,various wearable device components developed through the corresponding laser processes are discussed,with an emphasis on chemical/physical sensors and energy devices.In addition,special attention is given to applications that use multiple laser sources or processes,which lay the foundation for the all-laser fabrication of wearable devices.

Molecular investigation into the transformation of recalcitrant dissolved organic sulfur in refinery sour water during stripping process

Refinery sour water primarily originates from the tops of towers in various units and coker condensate,and cannot be discharged directly to a wastewater treatment plant due to high levels of chemical oxygen demand(COD)and organic sulfur contents.Even after the recovery of H_(2)S from the sour water by the stripping process,the effluent still contains a high concentration of dissolved organic sulfur(DOS),which can have a huge bad influence.While chemical composition of dissolved organic matter(DOM)in refinery wastewater has been extensively studied,the investigation of recalcitrant DOS from sour waters remains unclear.In the present study,chemical composition of sour water DOMs(especially DOS)was investigated using fluorescence spectroscopy(excitation-emission matrix,EEM)and mass spectrometry,including gas chromatography-mass spectrometry(GC-MS)and high-resolution Orbitrap MS.The GC-MS and EEM results showed that volatile and low-aromaticity compounds were effectively removed during the stripping process,while compounds with high hydrophilicity and humification degree were found to be more recalcitrant.The Orbitrap MS results showed that weak-polar oxygenated sulfur compounds were easier to be removed than oxygenated compounds.However,the effluent still contained significant amounts of sulfur-containing compounds with multiple sulfur atoms,particularly in the form of highly unsaturated and aromatic compounds.The Orbitrap MS/MS results of CHOS-containing compounds from the effluent indicate that the sulfur atoms may exist as sulfonates,disulfide bonds,thioethers.Understanding the composition and structure of sour water DOS is crucial for the development of effective treatment processes that can target polysulfide compounds and minimize their impact on the environment.

Process design and intensification of multicomponent azeotropes special distillation separation via molecular simulation and system optimization

This work provides an overview of distillation processes,including process design for different distillation processes,selection of entrainers for special distillation processes,system integration and intensification of distillation processes,optimization of process parameters for distillation processes and recent research progress in dynamic control strategies.Firstly,the feasibility of using thermodynamic topological theories such as residual curve,phase equilibrium line and distillation boundary line to analyze different separation regions is discussed,and the rationality of distillation process design is discussed by using its feasibility.Secondly,the application of molecular simulation methods such as molecular dynamics simulation and quantum chemical calculation in the screening of entrainer is discussed for the extractive distillation process.The thermal coupling mechanism of different distillation processes is used to explore the process of different process intensifications.Next,a mixed integer nonlinear optimization strategy for the distillation process based on different algorithms is introduced.Finally,the improvement of dynamic control strategies for different distillation processes in recent years is summarized.This work focuses on the application of process intensification and system optimization in the design of distillation process,and analyzes the challenges,prospects,and development trends of distillation technology in the separation of multicomponent azeotropes.

Insight of Natural Compounds Halimane Diterpenoids against Mycobacterium tuberculosis: Virtual Screening, DFT, Drug-Likeness, and Molecular Dynamics Approach

In the purpose to design novel antituberculosis (anti-TB) drugs agents against Mycobacterium tuberculosis (Mtb), we have built a molecular library around 42 Halimane Diterpenoids isolated from natural sources. Two Mtb enzymes drug targets (Mtb Mycothiol S-transferase and Mtb Homoserine transacetylase) have been adopted. The pharmacological potential was investigated through molecular docking, molecular dynamics simulation, density functional theory (gas phase and water) and ADMET analysis. Our results indicate that (2R,5R,6S)-1,2,3,4,5,6,7,8-octahydro-5-((E)-5-hydroxy-3-methylpent-3-enyl)-1,1,5,6-tetramethylnaphtha-lene-2-ol (compound 20) has displays higher docking score with each of the selected drug targets. In addition, this molecule exhibits a satisfactory drug potential activity and a good chemical reactivity. Its improved kinetic stability in the Mtb Mycothiol S-transferase enzyme reflects its suitability as a novel inhibitor of Mtb growth. This molecule has displayed a good absorption potential. Our results also show that its passive passage of the intestinal permeability barrier is more effective than that of first-line treatments (ethambutol, isoniazid). In the same way, this anti-TB druglikeness has shown to be able to cross the blood brain barrier.

Molecular Identification of Mycobacterium Strains Responsible of Bovine Tuberculosis Cases in Bobo-Dioulasso Slaughterhouse, Burkina Faso

Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.

NADARAYA-WATSON ESTIMATORS FOR REFLECTED STOCHASTIC PROCESSES

We study the Nadaraya-Watson estimators for the drift function of two-sided reflected stochastic differential equations.The estimates,based on either the continuously observed process or the discretely observed process,are considered.Under certain conditions,we prove the strong consistency and the asymptotic normality of the two estimators.Our method is also suitable for one-sided reflected stochastic differential equations.Simulation results demonstrate that the performance of our estimator is superior to that of the estimator proposed by Cholaquidis et al.(Stat Sin,2021,31:29-51).Several real data sets of the currency exchange rate are used to illustrate our proposed methodology.

Molecular phylogeny and taxonomy of Phlomoides(Lamiaceae subfamily Lamioideae)in China:Insights from molecular and morphological data

Phlomoides,with 150-170 species,is the second largest and perhaps most taxonomically challenging genus within the subfamily Lamioideae(Lamiaceae).With about 60 species,China is one of three major biodiversity centers of Phlomoides.Although some Phlomoides species from China have been included in previous molecular phylogenetic studies,a robust and broad phylogeny of this lineage has yet to be completed.Moreover,given the myriad new additions to the genus,the existing infrageneric classification needs to be evaluated and revised.Here,we combine molecular and morphological data to investigate relationships within Phlomoides,with a focus on Chinese species.We observed that plastid DNA sequences can resolve relationships within Phlomoides better than nuclear ribosomal internal and external transcribed spacer regions(nrITS and nrETS).Molecular phylogenetic analyses confirm the monophyly of Phlomoides,but most previously defined infrageneric groups are not monophyletic.In addition,morphological analysis demonstrates the significant taxonomic value of eight characters to the genus.Based on our molecular phylogenetic analyses and morphological data,we establish a novel section Notochaete within Phlomoides,and propose three new combinations as well as three new synonyms.This study presents the first molecular phylogenetic analyses of Phlomoides in which taxa representative of the entire genus are included,and highlights the phylogenetic and taxonomic value of several morphological characters from species of Phlomoides from China.Our study suggests that a taxonomic revision and reclassification for the entire genus is necessary in the future.

Multimodal Data-Driven Reinforcement Learning for Operational Decision-Making in Industrial Processes

Dear Editor, This letter proposes a multimodal data-driven reinforcement learning-based method for operational decision-making in industrial processes. Due to the frequent fluctuations of feedstock properties and operating conditions in the industrial processes, existing data-driven methods cannot effectively adjust the operational variables. In addition, multimodal data such as images, audio.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

An Interpretable Light Attention-Convolution-Gate Recurrent Unit Architecture for the Highly Accurate Modeling of Actual Chemical Dynamic Processes

To equip data-driven dynamic chemical process models with strong interpretability,we develop a light attention–convolution–gate recurrent unit(LACG)architecture with three sub-modules—a basic module,a brand-new light attention module,and a residue module—that are specially designed to learn the general dynamic behavior,transient disturbances,and other input factors of chemical processes,respectively.Combined with a hyperparameter optimization framework,Optuna,the effectiveness of the proposed LACG is tested by distributed control system data-driven modeling experiments on the discharge flowrate of an actual deethanization process.The LACG model provides significant advantages in prediction accuracy and model generalization compared with other models,including the feedforward neural network,convolution neural network,long short-term memory(LSTM),and attention-LSTM.Moreover,compared with the simulation results of a deethanization model built using Aspen Plus Dynamics V12.1,the LACG parameters are demonstrated to be interpretable,and more details on the variable interactions can be observed from the model parameters in comparison with the traditional interpretable model attention-LSTM.This contribution enriches interpretable machine learning knowledge and provides a reliable method with high accuracy for actual chemical process modeling,paving a route to intelligent manufacturing.

Lithium Ion Transport Environment by Molecular Vibrations in Ion-Conducting Glasses

Controlling Li ion transport in glasses at atomic and molecular levels is key to realizing all-solid-state batteries,a promising technology for electric vehicles.In this context,Li_(3)PS_(4)glass,a promising solid electrolyte candidate,exhibits dynamic coupling between the Li^(+)cation mobility and the PS_(4)^(3-)anion libration,which is commonly referred to as the paddlewheel effect.In addition,it exhibits a concerted cation diffusion effect(i.e.,a cation-cation interaction),which is regarded as the essence of high Li ion transport.However,the correlation between the Li^(+)ions within the glass structure can only be vaguely determined,due to the limited experimental information that can be obtained.Here,this study reports that the Li ions present in glasses can be classified by evaluating their valence oscillations via Bader analysis to topologically analyze the chemical bonds.It is found that three types of Li ions are present in Li_(3)PS_(4)glass,and that the more mobile Li ions(i.e.,the Li3-type ions)exhibit a characteristic correlation at relatively long distances of 4.0-5.0A.Furthermore,reverse Monte Carlo simulations combined with deep learning potentials that reproduce X-ray,neutron,and electron diffraction pair distribution functions showed an increase in the number of Li3-type ions for partially crystallized glass structures with improved Li ion transport properties.Our results show order within the disorder of the Li ion distribution in the glass by a topological analysis of their valences.Thus,considering the molecular vibrations in the glass during the evaluation of the Li ion valences is expected to lead to the development of new solid electrolytes.

Comprehensive understanding of glioblastoma molecular phenotypes:classification,characteristics,and transition

Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.