Review on analytical technologies and applications in metabolomics

Over the past decade,the swift advancement of metabolomics can be credited to significant progress in technologies such as mass spectrometry,nuclear magnetic resonance,and multivariate statistics.Currently,metabolomics garners widespread application across diverse fields including drug research and development,early disease detection,toxicology,food and nutrition science,biology,prescription,and chinmedomics,among others.Metabolomics serves as an effective characterization technique,offering insights into physiological process alterations in vivo.These changes may result from various exogenous factors like environmental conditions,stress,medications,as well as endogenous elements including genetic and protein-based influences.The potential scientific outcomes gleaned from these insights have catalyzed the formulation of innovative methods,poised to further broaden the scope of this domain.Today,metabolomics has evolved into a valuable and widely accepted instrument in the life sciences.However,comprehensive reviews focusing on the sample preparation and analytical methodologies employed in metabolomics within the life sciences are surprisingly scant.This review aims to fill that gap,providing an overview of current trends and recent advancements in metabolomics.Particular emphasis is placed on sample preparation,sophisticated analytical techniques,and their applications in life science research.

Relaxin-encapsulated polymeric metformin nanoparticles remodel tumor immune microenvironment by reducing CAFs for efficient triple-negative breast cancer immunotherapy

Cancer-associated fibroblasts(CAFs)are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment,leading to the failure of triple-negative breast cancer(TNBC)immunotherapy.Therefore,depleting CAFs may enhance the effect of immunotherapy(such as PD-L1 antibody).Relaxin(RLN)has been demonstrated to significantly improve transforming growth factor-β(TGF-β)induced CAFs activation and tumor immunosuppressive microenvironment.However,the short half-life and systemic vasodilation of RLN limit its in vivo efficacy.Here,plasmid encoding relaxin(pRLN)to locally express RLN was delivered with a new positively charged polymer named polymeric metformin(PolyMet),which could increase gene transfer efficiency significantly and have low toxicity that have been certified by our lab before.In order to improve the stability of pRLN in vivo,this complex was further formed lipid poly-γ-glutamic acid(PGA)/PolyMetpRLN nanoparticle(LPPR).The particle size of LPPR was 205.5±2.9 nm,and the zeta potential was+55.4±1.6 mV.LPPR displayed excellent tumor penetrating efficacy and weaken proliferation of CAFs in 4T1luc/CAFs tumor spheres in vitro.In vivo,it could reverse aberrantly activated CAFs by decreasing the expression of profibrogenic cytokine and remove the physical barrier to reshape the tumor stromal microenvironment,which enabled a 2.2-fold increase in cytotoxic T cell infiltration within the tumor and a decrease in immunosuppressive cells infiltration.Thus,LPPR was observed retarded tumor growth by itself in the 4T1 tumor bearing-mouse,and the reshaped immune microenvironment further led to facilitate antitumor effect when it combined with PD-L1 antibody(aPD-L1).Altogether,this study presented a novel therapeutic approach against tumor stroma using LPPR to achieve a combination regimen with immune checkpoint blockade therapy against the desmoplastic TNBC model.

Chronic pre-treatment with memantine prevents amyloid-beta protein-mediated long-term potentiation disruption

Previous studies indicate that memantine, a low-affinity N-methyI-D-aspartate receptor antagonist exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.

Study on hydrodynamic diffusion law of the swelling particle slurry in karst pipeline

The swelling particle grouting material has demonstrated remarkable plugging effectiveness in high-pressure and large-flow burst water within karst pipelines.Currently,current research on the rheolog-ical model,flow computation theory,and plugging mechanism of this material is lacking.The conven-tional grouting slurry diffusion process,using the liquid-liquid two-phase flow method,fails to accurately simulate high solubility slurry and particle swelling.To address these limitations,this study established a precise constitutive model to describe the swelling particle slurry diffusion process in dynamic water.Additionally,a coupling calculation method was proposed to analyze the spatiotemporal heterogeneity of viscosity during slurry diffusion by considering the migration of slurry and the changes in viscosity.To investigate the interaction between particle swelling and flow field changes,a Compu-tational Fluid Dynamics-Discrete Element Method(CFD-DEM)coupling model was developed for the diffusion of swelling particle slurry.It is demonstrated that slurry viscosity increases exponentially within the diffusion front as the particle swelling rate rises,and the drag force exhibits an intriguing behavior of initially increasing and then decreasing as the slurry flows through the pipeline.Further-more,the CFD-DEM coupling model proved to be more accurate in describing viscosity distribution and diffusion distance compared to the finite element solution.The primary objective of this paper is to reveal the plugging mechanism and provide theoretical support for the engineering application of the swelling particle grouting material.

Coronavirus disease 2019 epidemic prediction in Shanghai under the “dynamic zero-COVID policy”using time-dependent SEAIQR model

It’s urgently needed to assess the COVID-19 epidemic under the“dynamic zero-COVID policy”in China,which provides a scientific basis for evaluating the effectiveness of this strategy in COVID-19 control.Here,we developed a time-dependent susceptible-exposed-asymptomatic-infected-quarantined-remov ed(SEAIQR)model with stage-specific interventions based on recent Shanghai epidemic data,considering a large number of asymptomatic infectious,the changing parameters,and control procedures.The data collected from March 1st,2022 to April 15th,2022 were used to fit the model,and the data of subsequent 7 days and 14 days were used to evaluate the model performance of forecasting.We then calculated the effective regeneration number(Rt)and analyzed the sensitivity of different measures scenarios.Asymptomatic infectious accounts for the vast majority of the outbreaks in Shanghai,and Pudong is the district with the most positive cases.The peak of newly confirmed cases and newly asymptomatic infectious predicted by the SEAIQR model would appear on April 13th,2022,with 1963 and 28,502 cases,respectively,and zero community transmission may be achieved in early to mid-May.The prediction errors for newly confirmed cases were considered to be reasonable,and newly asymptomatic infectious were considered to be good between April 16th to 22nd and reasonable between April 16th to 29th.The final ranges of cumulative confirmed cases and cumulative asymptomatic infectious predicted in this round of the epidemic were 26,477~47,749 and 402,254~730,176,respectively.At the beginning of the outbreak,Rt was 6.69.Since the implementation of comprehensive control,Rt showed a gradual downward trend,dropping to below 1.0 on April 15th,2022.With the early implementation of control measures and the improvement of quarantine rate,recovery rate,and immunity threshold,the peak number of infections will continue to decrease,whereas the earlier the control is implemented,the earlier the turning point of the epidemic will arrive.The proposed time-dependent SEAIQR dynamic model fits and forecasts the epidemic well,which can provide a reference for decision making of the“dynamic zero-COVID policy”.