A proteomic landscape of pharmacologic perturbations for functional relevance

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Investigating College Students’ Diet and Physical Activity Behaviors Regarding Non-Communicable Diseases Prevention in China

We aimed to investigate if college students’ dietary and physical activity adhered to the Chinese Dietary Guidelines, the Composing Editorial Board of Physical Activity Guidelines, and WHO recommendation for NCDs prevention. Methods: A 3-day (2 weekdays and 1 weekend day) 24-hour (24-HRs) dietary recall was conducted to record details of participants’ food consumption. One-way analysis of variance (ANOVA) was applied to examine the influence of the identified demographic variables (including BMI, gender, major, family monthly income, and place of household registration) on the 8 food groups’ consumption. We analyzed the effect of the various demographic variables on sodium intake by the student’s t-test. The questionnaire, International Physical Activity Questionnaire (IPAQ)-Short Form, was utilized to assess participants’ physical activity (PA) level. The Wilcoxon-Mann-Whitney was applied to analyze participants’ physical activity. Results: Our research indicated participants consumed much fewer fruits and vegetables and excessive meats on average for both males and females regarding NCDs prevention. Conclusion: Participants’ dietary intake did not comply with the Chinese Dietary Guide-lines recommendation for chronic diseases prevention. Nutrition knowledge and health education are needed for college students. .

Anomalous metastable hcp Ni nanocatalyst induced by non-metal N doping enables promoted ammonia borane dehydrogenation

Developing high-performing non-noble transition metal catalysts for H_(2) evolution from chemical hydrogen storage materials is of great significance for the hydrogen economy system, yet challenging. Herein,we present for the first time that anomalous metastable hexagonal close-packed Ni nanoparticles induced by heteroatom N doping encapsulated in carbon(N-hcp-Ni/C) can exhibit admirable catalytic performance for ammonia borane(AB) dehydrogenation, prominently outperforming conventional fcc Ni counterpart with similar morphology and favorably presenting the state-of-the-art level.Comprehensive experimental and theoretical studies unravel that unusual hcp phase engineering of Ni together with N doping could induce charge redistribution and modulate electronic structure, thereby facilitating H_(2)O adsorption and expediting H_(2)O dissociation(rate-determining step). As a result, AB dehydrogenation can be substantially boosted with the assistance of N-hcp-Ni/C. Our proposed strategy highlights that unconventional crystal phase engineering coupled with non-metal heteroatom doping is a promising avenue to construct advanced transition metal catalysts for future renewable energy technologies.

Boosted urea electro-oxidation over Ni_(3)N-based nanocomposite via systematic regulation tactic

Exploiting high-efficiency Ni-based materials for electrocatalytic urea oxidation reaction(UOR) is critical for urea-related technologies.The catalytic site density,intrinsic activity,charge transfer,and mass diffusion determine overall electrocatalytic efficiency.Simultaneous modulation over the above four factors promises advanced electrocatalysis,yet challenging.Herein we propose a systematic regulation tactic over composition and geometric structure,constructing a nanocomposite comprising Mn doped Ni_(3)N nanoparticles anchored on reduced graphene oxide(rGO/Mn-Ni_(3)N),achieving elegant integration of four design principles into one,thereby eminently boosting UOR.Particularly,Mn doping in Ni_(3)N can modulate electronic state to induce intrinsic activity regulation.Combining metallic Mn-Ni_(3)N with rGO to engineer hierarchical architecture not only promotes charge transfer,but also enriches active site population.Intriguingly,improved hydrophilicity could impart better electrolyte penetration and gas escape.Consequently,such system-optimized rGO/Mn-Ni_(3)N demonstrates state-of-the-art-level UOR electrocatalysis.This work offers a novel paradigm to create advanced catalysts via systematic and integrated modulation.

Separation of light hydrocarbons with ionic liquids: A review

Light hydrocarbons(C1–C4) are fundamental raw materials in the petroleum and chemical industry. Separation and purification of structurally similar paraffin/olefin/alkyne mixtures are important for the production of highpurity or even polymer-grade light hydrocarbons. However, traditional methods such as cryogenic distillation and solvent absorption are energy-intensive and environmentally unfriendly processes. Ionic liquids(ILs) as a new alternative to organic solvents have been proposed as promising green media for light hydrocarbon separation due to their unique tunable structures and physicochemical properties resulting from the variations of the cations and anions such as low volatility, high thermal stability, large liquidus range, good miscibility with light hydrocarbons, excellent molecular recognition ability and adjustable hydrophylicity/hydrophobicity. In this review, the recent progresses on the light hydrocarbon separation using ILs are summarized, and some parameters of ILs that influence the separation performance are discussed.

Drug repurposing for cancer treatment through global propagation with a greedy algorithm in a multilayer network

Objective:Drug repurposing,the application of existing therapeutics to new indications,holds promise in achieving rapid clinical effects at a much lower cost than that of de novo drug development.The aim of our study was to perform a more comprehensive drug repurposing prediction of diseases,particularly cancers.Methods:Here,by targeting 4,096 human diseases,including 384 cancers,we propose a greedy computational model based on a heterogeneous multilayer network for the repurposing of 1,419 existing drugs in Drug Bank.We performed additional experimental validation for the dominant repurposed drugs in cancer.Results:The overall performance of the model was well supported by cross-validation and literature mining.Focusing on the top-ranked repurposed drugs in cancers,we verified the anticancer effects of 5 repurposed drugs widely used clinically in drug sensitivity experiments.Because of the distinctive antitumor effects of nifedipine(an antihypertensive agent)and nortriptyline(an antidepressant drug)in prostate cancer,we further explored their underlying mechanisms by using quantitative proteomics.Our analysis revealed that both nifedipine and nortriptyline affected the cancer-related pathways of DNA replication,the cell cycle,and RNA transport.Moreover,in vivo experiments demonstrated that nifedipine and nortriptyline significantly inhibited the growth of prostate tumors in a xenograft model.Conclusions:Our predicted results,which have been released in a public database named The Predictive Database for Drug Repurposing(PAD),provide an informative resource for discovering and ranking drugs that may potentially be repurposed for cancer treatment and determining new therapeutic effects of existing drugs.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia:Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia(VaD)is the second commonest type of dementia which lacks of efficient treatments currently.Neuroinflammation as a prominent pathological feature of VaD,is highly involved in the development of VaD.In order to verify the therapeutic potential of PDE1 inhibitors against VaD,the anti-neuroinflammation,memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a.Also,the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored.Furthermore,to optimize the drug-like properties of 4a,especially for metabolic stability,15 derivatives were designed and synthesized.As a result,candidate 5f,with a potent IC50 value of 4.5 nmol/L against PDE1C,high selectivity over PDEs,and remarkable metabolic stability,efficiently ameliorated neuron degeneration,cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis.These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Herein,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical responses.The multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in PCa.Through the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary cells.We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations.Surprisingly,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model.Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

Efficiently identifying coalbed methane enrichment areas by detecting and locating low-frequency signals in the coal mine

Low-frequency signals have been widely found in the conventional oil/gas field and volcanic region as well as during hydraulic fracturing of unconventional oil/gas reservoirs.Their generation mechanism has been ascribed to the flow of gas/fluid in the fractures,which can induce the Krauklis wave around fractures and can further excite low-frequency seismic body wave signals at diffraction points.Thus,it is theoretically feasible to determine the gas/fluid enrichment areas and migration pathways by locating the low-frequency signals.Here we have utilized a surface dense seismic array deployed above the Sijiazhuang coal mine in Shanxi province to detect and locate such low-frequency signals that are dominant in the frequency range of 1.5–4.0 Hz.Waveform migrationbased location method is employed to locate these signals that have low signal to noise ratios.We further compare the distribution of low-frequency signals and coalbed methane concentrations that are estimated based on ambient noise tomography result with the same seismic array.The spatial consistency between low-frequency signals and coalbed methane enrichment areas suggests that detecting and locating low-frequency signals with a surface seismic array is an efficient way to identify gas enrichment areas and potential gas migration pathways.

Construction of anion-functionalized hypercrosslinked ionic porous polymers for efficient separation of bioactive molecules

Porous ionic polymers have demonstrated great potential for high-performance separation by the merits of their unique molecular recognition,but the preparation of anion-functionalized ionic polymers for the separation of bioactive molecules with highly similar structures remains a challenge.Here,through the facile Friedel-Crafts alkylation between benzylimidazole ionic liquids(ILs)and crosslinkers,several anion-functionalized hypercrosslinked ionic porous polymers(HIPs)are reported,which are well decorated with strongly basic carboxylate anions as well as feature tubular morphology and excellent thermal stability.High adsorption capacity(103.6 mg g^(−1) for tocopherol homologues)and selectivity(S_(βγ/α),4.26;S_(δ/α),3.19)for bioactive compounds with high structural similarity have been realized,superior to those of commercial adsorbents,hypercrosslinked polymer without ILs,and HIPs with common ILs.This study manifests a new synthetic strategy and rational molecular design for functionalized adsorbents,as well as offers new opportunities to enable high-performance separation.

Study of the automotive aerodynamic performance affected by entrance structure of forecabin

Recently,the requirement for cooling capacity decreased when the driving energy changed from liquid fuel to lithium batteries.Therefore,the structure and location of the forecabin could be adjusted based on the aerody-namic performance.The current study conducted a significant number of simulations in order to find out the effects of the internal flow through forecabin in an Ahmed body.The following conclusions have been identi-fied:1,The flow through the forecabin would always increase the resistance of the entire body,and the drag coefficient increases,on average,by approximately 85%.2,When the aspect ratio is higher or the position of the inlet opening is lower,the total drag coefficient is lower due to a weaker vortex strength,a simpler vortex structure and a relatively simple flow.3,The existence of the forecabin will largely increase the oscillation fre-quency of the flow field by approximately 15 times compared to the original Ahmed model.Finally,the high drag coefficient moment always appears to be due to the formation of more complex or intense vortex motion.These conclusions can offer useful results and references for the structural design of the front cabin for new energy vehicles.