Advances and Challenges of Exosome Metabolomics in Body Fluids

Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.

Hydroxyapatite Coatings on Titanium Prepared by Electrodeposition in a Modified Simulated Body Fluid

Hydroxyapatite coatings were directly prepared on anodized titanium by electro-deposition method in a modified simulated body fluid.The configuration,structure and bioactivity of the coating were investigated with scanning electron microscopy(SEM),X-ray diffraction analyzer(XRD)and Fourier transform infrared spectros-copy(FTIR)techniques.The results demonstrated that pure and homogeneous hydroxyapatite coating can be obtained without any post-treatment.The prepared coating showed good bioactivity in simulated body fluid(SBF).The time required for a fully covered dense hydroxyapatite coatings was 4 days immersion in SBF.

Numerical simulation of heat release performance of filling body under condition of heat extracted by fluid flowing in buried tube

It is the basic requirement of the synergetic exploitation of deep mineral resources and geothermal resources to arrange the heat transfer tube in filling body. The heat release performance of filling body directly impacts on the exploiting efficiency of geothermal energy. Based on heat transfer theory, a three-dimensional unsteady heat transfer model of filling body is established by using FLUENT simulation software. Taking the horizontal U-shaped buried pipe as research object, the variation of temperature field in filling body around buried pipe is analyzed during the heat release process of filling body;the initial temperature of filling body, the diameter of buried pipe, the inlet temperature and inlet velocity of heat transfer fluid influencing of coupling heat transfer, which exists between heat transfer fluid and surrounding filling body within a certain axial distance of buried tube, and influencing of temperature difference between inlet and outlet of heat transfer fluid and on heat transfer performance of filling body are also discussed. It not only lays a theoretical foundation for the synergetic exploitation of mineral resources and geothermal energy in deep mines, but also provides a reference basis for the arrangement of buried pipes in filling body as well as the selection of working conditions for heat transfer fluid.

Corrosion fatigue of the extruded Mg-Zn-Y-Nd alloy in simulated body fluid

Magnesium alloys were considered to be used as biodegradable implants due to their biocompatibility,biodegradability and nontoxicity.However,under the simultaneous action of corrosive environment and mechanical loading in human body,magnesium alloys are easy to be affected by corrosion fatigue and stress corrosion cracking.In this work,the fatigue behavior of the extruded Mg-Zn-Y-Nd alloy used for vascular stents was studied both in air and in simulated body fluid(SBF).It was revealed that the fatigue limit of as-extruded Mg-Zn-Y-Nd alloy in air is about 65 MPa at 10^7 cycles,while there is no limit in SBF and shows a linear relationship between the fatigue life and stress amplitudes.The fatigue crack source in air was formed by the inclusions and defects.However,the stress corrosion and hydrogen embrittlement are the main reasons for the formation of the fatigue initial crack source in SBF.

Understanding the effects of excimer laser treatment on corrosion behavior of biodegradable Mg-1Ca alloy in simulated body fluid

In this study,a KrF excimer laser was used to modify the biodegradable Mg-1Ca alloy and the time-evolution degradation behavior of the alloy before and after laser treatment was investigated in simulated body fluid(SBF)solution using immersion tests and electrochemical impedance spectroscopy(EIS).A 5μm melted layer with a homogeneous microstructure and an MgO film on the surface were achieved by laser radiation.Corrosion observations(hydrogen evolution,morphology and corrosion products)and EIS results revealed an improvement of corrosion resistance after laser treatment for 48 h.It was found a two-layer structure developed after 2 h immersion on both the untreated and laser-treated alloys,but the sequence of forming the two layers was opposite and greatly influenced by the laser-treated layer.The time-evolution corrosion processes on the untreated and laser-treated alloys were discussed,providing a better understanding of corrosion behavior of biodegradable Mg alloys modified by excimer laser.

Calcium phosphate deposition on surface of porous and dense TiNi alloys in simulated body fluid

Porous and dense TiNi alloys were successfully fabricated by powder metallurgy(P/M) method, and to further improve their surface biocompatibility, surface modification techniques including grind using silicon-carbide(SiC) paper, acid etching and alkali treatment were employed to produce either irregularly rough surface or micro-porous surface roughness. X-ray diffractometry(XRD), scanning electron microscopy(SEM) and energy dispersive X-ray spectroscopy(EDX) attached to SEM were used to characterize surface structure and the Ca-P coatings. Effects of the above surface treatments on the surface morphology, apatite forming ability were systematically investigated. Results indicate that all the above surface treatments increase the apatite forming ability of TiNi alloys in varying degrees when soaked in simulated body fluid(SBF). More apatite coatings formed on TiNi samples sintered at 1050℃ and 1100℃ due to their high porosity and pure TiNi phase that is beneficial to heterogeneous nucleation. Furthermore, more uniform apatite was fabricated on the sample sintered from the mixture of Ni and Ti powders.

Raman Spectroscopy for Forensic Identification of Body Fluid Traces: Method Validation for Potential False Negatives Caused by Blood-Affecting Diseases

Two critical issues in forensic science are identifying body fluid traces found at crime scenes and preserving them for DNA analysis. However, the majority of current biochemical tests for body fluid identification, which are applicable at the crime scene, are presumptive and destructive to the sample. Raman Spectroscopy provides a suitable alternative to current methods as a nondestructive, confirmatory, and potentially in field method. Our laboratory has developed a chemometric model for the identification of five main body fluids using Raman spectroscopy. This model was developed using samples obtained from healthy donors. Thus, it is of most importance for the forensic application of the method to validate its performance for donors with diseases that might affect the biochemical composition of body fluids. In this study, the developed method was validated using peripheral blood samples acquired from donors with Celiac Disease, Sickle Cell Anemia, and Type 2 Diabetes. It was shown that the method correctly identified all samples as peripheral blood indicating that no false positives could occur because the blood traces were originated from donors suffering from the diseases.

Bone-like apatite formation on HA/316L stainless steel composite surface in simulated body fluid

HA/316L stainless steel(316L SS) biocomposites were prepared by hot-pressing technique. The formation of bone-like apatite on the biocomposite surfaces in simulated body fluid(SBF) was analyzed by digital pH meter,plasma emission spectrometer,scanning electron microscope(SEM) and energy dispersive X-ray energy spectrometer(EDX). The results indicate that the pH value in SBF varies slightly during the immersion. It is a dynamic process of dissolution-precipitation for the formation of apatite on the surface. With prolonging immersion time,Ca and P ion concentrations increase gradually,and then approach equilibrium. The bone-like apatite layer forms on the composites surface,which possesses benign bioactivity and favorable biocompatibility and achieves osseointegration,and can provide firm fixation between HA60/316L SS composite implants and human body bone.

Characterization and wear resistance of macro-arc oxidation coating on magnesium alloy AZ91 in simulated body fluids

The mechanical characteristics of the macro-arc oxidation(MAO) coating on Mg alloy AZ91 were examined by means of nano scratch tester.The corrosion and erosion corrosion behavior of AZ91 with and without MAO coating were investigated by using potentiodynamic electrochemical technique and micro-abrasion tribometer in simulated body fluids,respectively.The influence of HCO_3^- ions on the erosion corrosion was discussed.The results show that the coating and its substrate are in a pronounced bond.The MAO coating increases 1-2 orders of magnitude of the corrosion resistance of AZ91 alloy.HCO_3^- ions enhance the corrosion rates of the AZ91 alloys more significantly than the alloys with MAO coating.However,there exists an obvious passivation process of AZ91 without coating in the HCO_3^- solutions.Moreover,an MgCO_3 film formed in HCO_3^- containing solutions leads to an enhancement in micro-wear resistance.MAO coating deteriorates the erosion corrosion resistance of AZ91 alloy due to the formation of oxidation debris resulted from the broken MAO coating.

Messenger RNA Profiling for Forensic Body Fluid Identification： Research and Applications

Identifying the origin of body fluids left at a crime scene can give a significant insight into crime scene reconstruction by supporting a link between sample donors and actual criminal acts.However,the conventional body fluid identification methods are prone to various limitations,such as time consumption,intensive labor,nonparallel manner,varying degrees of sensitivity and limited specificity.Recently,the analysis of cell-specific messenger RNA expression(mRNA profiling)has been proposed to supplant conventional methods for body fluid identification.Since 2011,the collaborative exercises have been organized by the European DNA Profiling Group(EDNAP)in order to evaluate the robustness and reproducibility of mRNA profiling for body fluid identification.The major advantages of mRNA profiling,compared to the conventional methods,include higher sensitivity,greater specificity,the ability of detecting several body fluids in one multiplex reaction,and compatibility with current DNA extraction and analysis procedure.In the current review,we provided an overview of the present knowledge and detection methodologies of mRNA profiling for forensic body fluid identification and discussed its possible practical application to forensic casework.

Reflections on the Mechanism of Calcium Phosphate Nucleation on Titanium in Simulated Body Fluids

The results and main findings of studies reported in the literature in relation to the deposition of calcium phosphate on Ti in simulated body fluids are summarized. The effects of the surface hydroxyl groups and the sign of surface charge on the nucleation of calcium phosphate are reviewed. One major controversy among the conclusions of different studies is the order of adsorption of the calcium ions and the phosphate ions in the initial stage of immersion. A simple model based on the amphoteric nature of the hydroxyl groups on Ti is proposed in an attempt to delineate the nucleation process for calcium phosphate on Ti in simulated body fluids. HPO4^2- ions interact with the hydroxyl groups via ion exchange and/or electrostatic attraction, and Ca^2＋ ions, via electrostatic attraction only. There is no preferential order of adsorption. Seemingly inconsistent results in different studies possibly arise from different prior treatments of the samples, which affect the adsorption properties.

Formation of Apatite in Simulated Body Fluid

It is confirmed that the essential condition for glasses and glass-ceramics to bond to living bone is the formation of an apatite layer on their surfaces in the body.It is proposed that a hydrated silica formed on the surfaces of these materials in the body plays an important role in forming the surface apatite layer,which has not been proved yet.It is shown experimentally that a pure hydrated silica gel can induce the apatite formation on its surface in a simulated body fluid when its starting pH is increased from 7.2 to 7.4.

Evaluation of Bioactive Properties of α and β Wollastonite Bioceramics Soaked in a Simulated Body Fluid

Dense natural wollastonite bioceramics (CaSiO3) were prepared by a sintering method, varying the pressing load and sintering temperature, in order to obtain different phases of wollastonite, and different physical properties in the materials. The products were characterized by TGA-DTA, XRD, FT-IR, SEM-EDS, TEM and XPS techniques. The results indicate the presence of two polymorphic phases of wollastonite, the β-wollastonite and α-wollastonite with a transition temperature of the β phase to α phase at approximately 1250℃. These materials were soaked in a simulated body fluid (SBF) during 1, 2 and 3 weeks, to study their solubility and bioactivity. The effect of different wollastonite phases on the solubility of Ca and Si, as well as the capacity of producing layers of “newly formed apatite” on the surfaces of these materials in SBF solution were analyzed.

Occupational exposures to blood and body fluids (BBF): Assessment of knowledge, attitude and practice among health care workers in general hospitals in Lebanon

Healthcare workers (HCWs) who are employed in traditional health care workplaces face a serious danger that may threaten their life;it is their exposure to blood and body fluids (BBF). In Lebanon, the introduction of a hospital accreditation system has put a particular emphasis on staff safety, and on the evaluation of professional practice (EPP) programs. Methods: A cross-sectional survey was conducted amongst 277 HCWs working in 4 general hospitals in South Lebanon. Objective: 1) describe the prevalence and the risk factors for occupational exposure to BBF among HCWs;2) evaluate knowledge, attitude, and practices of HCW concerning blood-borne pathogens and adherence to universal safety precautions. Results: The mean age of the respondents was 32.14 years (SD = 10.33), 57.4% were females. 43.3% of HCWs expressed that they use gloves all the time for every activeity of care. 67.1% were aware that needles should not be recapped after use;registered nurses and nursing students were more aware than physicians and nursing assistants (nurse) in this subject. 30% of HCWs declared having had at least one occupational exposure to BBF;62.7% of all accidental exposure was reported to the department responsible for managing exposures. Percutaneous injuries were the most frequently reported. Vaccination coverage was 88.4% for hepatitis B, and 48.4% against influenza. The source patient was tested in 43.4% of reported BBF exposures. Accidental exposure to BBF was more frequent in older people (OR = 3.42;p = 0.03) and the more experienced. Subjects working in intensive care unit ward reported more exposure to BBF (OR = 3;p = 0.04). Participants incurring exposure to BBF resorted to different measures after the injury suggesting a lack of a uniform policy for post-exposure prophylaxis. Conclusion: Exposure to BBF represents an important and frequently preventable occupational hazard for HCWs in Lebanon that requires continuous EPP of HCWs, and a comprehensive approach for prevention and management.

Critical biomarkers of hepatocellular carcinoma in body fluids and gut microbiota

Hepatocellular carcinoma(HCC)is the most prevalent primary liver cancer and one of the major causes of cancer-related death.The development of specific noninvasive or diagnostic markers from blood,urine and feces may represent a valuable tool for detecting HCC at an early stage.Biomarkers are considered novel potential targets for therapeutic intervention.It helps in the prediction of prognosis or recurrence of HCC,and also assist in the selection of appropriate treatment modality.We summarize the most relevant existing data about various biomarkers that play a key role in the progression of HCC.

α-Synuclein pathology from the body to the brain:so many seeds so close to the central soil

α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

Identification of Mixtures of Two Types of Body Fluids Using the Multiplex Methylation System and Random Forest Models

Objective Body fluid mixtures are complex biological samples that frequently occur in crime scenes,and can provide important clues for criminal case analysis.DNA methylation assay has been applied in the identification of human body fluids,and has exhibited excellent performance in predicting single-source body fluids.The present study aims to develop a methylation SNaPshot multiplex system for body fluid identification,and accurately predict the mixture samples.In addition,the value of DNA methylation in the prediction of body fluid mixtures was further explored.Methods In the present study,420 samples of body fluid mixtures and 250 samples of single body fluids were tested using an optimized multiplex methylation system.Each kind of body fluid sample presented the specific methylation profiles of the 10 markers.Results Significant differences in methylation levels were observed between the mixtures and single body fluids.For all kinds of mixtures,the Spearman’s correlation analysis revealed a significantly strong correlation between the methylation levels and component proportions(1:20,1:10,1:5,1:1,5:1,10:1 and 20:1).Two random forest classification models were trained for the prediction of mixture types and the prediction of the mixture proportion of 2 components,based on the methylation levels of 10 markers.For the mixture prediction,Model-1 presented outstanding prediction accuracy,which reached up to 99.3%in 427 training samples,and had a remarkable accuracy of 100%in 243 independent test samples.For the mixture proportion prediction,Model-2 demonstrated an excellent accuracy of 98.8%in 252 training samples,and 98.2%in 168 independent test samples.The total prediction accuracy reached 99.3%for body fluid mixtures and 98.6%for the mixture proportions.Conclusion These results indicate the excellent capability and powerful value of the multiplex methylation system in the identification of forensic body fluid mixtures.

Age-Related Surface Oxidases Shed into Body Fluids as Targets to Prevent Skin Aging and Reduce Cardiovascular Risk

Age-related Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchangers 3 (ENOX3) or age-related NADH oxidases (arNOX) are expressed at the cell surface as five members of the TM-9 superfamily, initially membrane anchored, all functionally similar, with the N-termini exposed at the cell’s exterior. ECTO-NOXes are cell surface proteins with both time-keeping CoQH2 [NAD(P)H] oxidase and protein disulfidethiol interchange activities. They are designated as ECTO-NOX proteins because of their localization on the outer surface of the plasma membrane and to distinguish them from the phox-NOXes of host defense. A ca. 30 kDa N-terminal fragment is cleaved and accumulates in body fluids (serum, saliva, urine, perspiration). arNOXes appear around age 30 and increase steadily thereafter. Reduced quinones, i.e., reduced coenzyme Q, of the plasma membrane are natural substrates. NAD(P)H is oxidized as an artificial substrate. In one phase of the arNOX cycle electrons are transferred to oxygen to generate superoxide. Substrates for the shed forms of arNOX appear to be proteins of body fluids. Circulating lipoproteins and skin matrix proteins emerge as potentially important health-related targets. Through oxidation of collagen, elastin and other proteins of the skin matrix, arNOXes are major contributors to skin aging through tyrosine and thiol oxidation and subsequent cross linking. The main destructive action of arNOX, however, may be to directly oxidize circulating lipoproteins. arNOX in the blood is structured as an integral component of the LDL particle through site-specific binding. As such, arNOXes are implicated as major risk factors for cardiovascular disease due to specific oxidation of LDLs. The superoxide produced and its conversion to hydrogen peroxide would be one part of the potentially destructive properties by contribution to lipid oxidation. Inhibition of arNOX proteins provides a rational basis for anti-aging interventions and their elimination as a major risk factor of atherogenesis.

COMMENTS ON TREATMENT OF OBESITY BASED ON SYNDROME DIFFERENTIATION OF BODY FLUID

Because of no exact name about obesity in traditional Chinese medicine, clinically there have no unified syndrome types about obesity. The present paper uses the original syndrome differentiation of body fluid and selects classical acupuncture and moxibustion prescriptions to treat obesity, which is conducive to further systematizing classical acupuncture and moxibustion prescriptions and providing sufficient basis for clinical popularization.

Alpha-synuclein in body fluids as a diagnostic biomarker for Parkinson’s disease

Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(SN)and the formation ofα-synuclein(α-syn)containing inclusion bodies(Lewy pathology)in the surviving neurons.Diagnosis of PD is still based on clinical features.However,owing to the complexity,heterogeneity,and overlapping of its symptoms with other Parkinsonian disorders,correct diagnosis of PD remains a challenge,especially in the early stages.Therefore,there is an urgent need for biomarkers that can help correctly diagnose PD,differentiate PD from other Parkinsonian disorders,monitor the progression of the disease,and evaluate the therapeutic efficacy.Various molecules have been investigated for their utility in diagnosing PD,among whichα-syn is the most extensively investigated one due to its close implication in the etiology and pathogenesis of PD and related diseases.During the past decade,various species ofα-syn,including total,oligomeric,and phosphorylatedα-syn in various tissues,have been investigated for their utility as a potential biomarker for PD diagnosis and differential diagnosis.Various forms ofα-syn in body fluids,including cerebrospinal fluid(CSF),blood plasma,and saliva,are among the ones that are extensively investigated,since the body fluids are relatively accessible compared to the peripheral tissues.The aim of this review is to summarize the progress of studies on the utility ofα-syn in body fluid as a biomarker for PD diagnosis and differential diagnosis.