ESMSec: Prediction of Secreted Proteins in Human Body Fluids Using Protein Language Models and Attention.

The secreted proteins of human body fluid have the potential to be used as biomarkers for diseases. These biomarkers can be used for early diagnosis and risk prediction of diseases, so the study of secreted proteins of human body fluid has great application value. In recent years, the deep-learning-based transformer language model has transferred from the field of natural language processing (NLP) to the field of proteomics, leading to the development of protein language models (PLMs) for protein sequence representation. Here, we propose a deep learning framework called ESM Predict Secreted Proteins (ESMSec) to predict three types of proteins secreted in human body fluid. The ESMSec is based on the ESM2 model and attention architecture. Specifically, the protein sequence data are firstly put into the ESM2 model to extract the feature information from the last hidden layer, and all the input proteins are encoded into a fixed 1000 × 480 matrix. Secondly, multi-head attention with a fully connected neural network is employed as the classifier to perform binary classification according to whether they are secreted into each body fluid. Our experiment utilized three human body fluids that are important and ubiquitous markers. Experimental results show that ESMSec achieved average accuracy of 0.8486, 0.8358, and 0.8325 on the testing datasets for plasma, cerebrospinal fluid (CSF), and seminal fluid, which on average outperform the state-of-the-art (SOTA) methods. The outstanding performance results of ESMSec demonstrate that the ESM can improve the prediction performance of the model and has great potential to screen the secretion information of human body fluid proteins.

Drug solubilization in dog intestinal fluids with and without administration of lipid-based formulations.

The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and the colloids formed in it. In this study we used molecular dynamics simulations to investigate solubilization patterns for three model drugs (carvedilol, felodipine and probucol) in dog intestinal fluid, a lipid-based formulation, and a mixture of both. We observed morphological transformations that lipids undergo due to the digestion process in the intestinal environment. Further, we evaluated the effect of bile salt concentration and observed the importance of interindividual variability. We applied two methods of estimating solubility enhancement based on the simulated data, of which one was in good qualitative agreement with the experimentally observed solubility enhancement. In addition to the computational simulations, we also measured solubility in i) aspirated dog intestinal fluid samples and ii) simulated canine intestinal fluid in the fasted state, and found there was no statistical difference between the two. Hence, a simplified dissolution medium suitable for in vitro studies provided physiologically relevant data for the systems explored. The computational protocol used in this study, coupled with in vitro studies using simulated intestinal fluids, can serve as a useful prescreening tool in the process of drug delivery strategies development.

Identification of the body fluid donor in mixtures through target mRNA cSNP sequencing.

In forensic practice, mixture stains containing various body fluids are common, presenting challenges for interpretation, particularly in multi-contributor mixtures. Traditional STR profiles face difficulties in such scenarios. Over recent years, RNA has emerged as a promising biomarker for body fluid identification, and mRNA polymorphism has shown excellent performance in identifying body fluid donors in previous studies. In this study, a massively parallel sequencing assay was developed, encompassing 202 coding region SNPs (cSNPs) from 45 body fluid/tissue-specific genes to identify both body fluid/tissue origin and the respective donors, including blood, saliva, semen, vaginal secretion, menstrual blood, and skin. The specificity was evaluated by examining the single-source body fluids/tissue and revealed that the same body fluid exhibited similar expression profiles and the tissue origin could be identified. For laboratory-generated mixtures containing 2-6 different components and mock case mixtures, the donor of each component could be successfully identified, except for the skin donor. The discriminatory power for all body fluids ranged from 0.997176329 (menstrual blood) to 0.99999999827 (blood). The concordance of DNA typing and mRNA typing for the cSNPs in this system was also validated. This cSNP typing system exhibits excellent performance in mixture deconvolution.

Effect of measurement procedure errors on assessing lung fluid via remote dielectric sensing system.

The study assessed the impact of procedural errors on the remote dielectric sensing system (ReDS), a non-invasive lung fluid assessment technology, in an Asian cohort. Healthy volunteers underwent ReDS measurements following manufacturer's instructions, with two consecutive measurements one minute apart. A subset of 20 participants had modified procedure settings. Reliability was measured using intraclass correlation coefficient (ICC). The study included 86 healthy volunteers, and all ReDS measurements fell within the recommended normal range. The intra-rater reliability of ReDS measurements was excellent, with an ICC of 0.968. Among the subset of 20 subjects, deviations in height and weight did not significantly affect ReDS values. However, deviations in chest size by ± 3 cm had a noticeable impact on ReDS measures, and incorrect station selection led to fluctuations in ReDS readings. In conclusion, the ReDS system demonstrated excellent intra-rater reliability and applicability in an Asian cohort. Procedural errors, such as chest size measurement and station selection, significantly influenced ReDS measurements. Adherence to standardized operating procedures is crucial to ensure accurate and consistent results. These findings highlight the importance of adherence to manufacturer instructions when utilizing ReDS for lung fluid assessment, thereby enhancing its reliability and clinical applicability.

MPXV DNA kinetics in bloodstream and other body fluids samples.

Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission.

Development of Rapid Bioactivity-Expressed Zr-50Ti Alloys by Surface Treatment with Modified Simulated Body Fluid.

Zr-50Ti alloys are promising biomaterials due to their excellent mechanical properties and low magnetic susceptibility. However, Zr-50Ti alloys do not inherently bond well with bone. This study aims to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic implant materials. Initially, the surface of Zr-50Ti alloys was treated with a sulfuric acid solution to create a microporous structure, increasing surface roughness and area. Subsequently, low crystalline calcium phosphate (L-CaP) precipitation was controlled by adding Mg2+ and/or CO32- ions in modified simulated body fluid (m-SBF). The treated Zr-50Ti alloys were then subjected to cold isostatic pressing to force m-SBF into the micropores, followed by incubation to allow L-CaP formation. The apatite-forming process was tested in simulated body fluid (SBF). The results demonstrated that the incorporation of Mg2+ and/or CO32- ions enabled the L-CaP to cover the entire surface of Zr-50Ti alloys within only one day. After short-term soaking in SBF, the L-CaP layer, modulated by Mg2+ and/or CO32- ions, formed a uniform hydroxyapatite (HA) coating on the surface of the Zr-50Ti alloys, showing potential for optimized bone integration. After soaking in SBF for 14 days, the bonding strength between the apatite layer and alloy has the potential to meet the orthopedic application requirement of 22 MPa. This study demonstrates an effective method to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic applications.

Sensing patches for biomarker identification in skin-derived biofluids.

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).

Smart Contact Lens for Colorimetric Visualization of Glucose Levels in the Body Fluid.

Frequent blood glucose monitoring is a crucial routine for diabetic patients. Traditional invasive methods can cause discomfort and pain and even pose a risk of infection. As a result, researchers have been exploring noninvasive techniques. However, a limited number of products have been developed for the market due to their high cost. In this study, we developed a low-cost, highly accessible, and noninvasive contact lens-based glucose monitoring system. We functionalized the surface of the contact lens with boronic acid, which has a strong but reversible binding affinity to glucose. To achieve facile conjugation of boronic acid, we utilized a functional coating layer called poly(tannic acid). The functionalized contact lens binds to glucose in body fluids (e.g., tear) and releases it when soaked in an enzymatic cocktail, allowing for the glucose level to be quantified through a colorimetric assay. Importantly, the transparency and oxygen permeability of the contact lens, which are crucial for practical use, were maintained after functionalization, and the lenses showed high biocompatibility. Based on the analysis of colorimetric data generated by the smartphone application and ultraviolet-visible (UV-vis) spectra, we believe that this contact lens has a high potential to be used as a smart diagnostic tool for monitoring and managing blood glucose levels.

Aptamer-based sensors for fluid biopsies of protein disease markers.

Fluid biopsy technology, characterized by its minimally invasive nature, speed, and continuity, has become a rapidly advancing and widely applied real-time diagnostic technique. Among various biomarkers, proteins represent the most abundant class of disease indicators. The sensitive and accurate detection of protein markers in bodily fluids is significantly influenced by the control exerted by recognition ligands. Aptamers, which are structurally dynamic functional oligonucleotides, exhibit high affinity, specific recognition of targets, and notable characteristics of high editability and modularity. These features make aptamer universal "recognition-capture" components, contribute to a significant leap in their applications within the biosensor domain. In this context, we provide a comprehensive review of the extensive application of aptamer-based biosensors in fluid biopsy. We systematically compile the characteristics and construction strategies of aptamer-based biosensors tailored for fluid biopsy, including aptamer sequences, affinity (KD), fluid background, sensing technologies, sensor construction strategies, incubation time, detection performance, and influencing factors. Furthermore, a comparative analysis of their advantages and disadvantages was conducted. In conclusion, we delineate and deliberate on prospective research trajectories and challenges that lie ahead in the realm of aptamer-based biosensors for fluid biopsy.

Spray-dried ternary bioactive glass microspheres: Direct and indirect structural effects of copper-doping on acellular degradation behavior.

Silicate-based bioactive glass nano/microspheres hold significant promise for bone substitution by facilitating osteointegration through the release of biologically active ions and the formation of a biomimetic apatite layer. Cu-doping enhances properties such as pro-angiogenic and antibacterial behavior. While sol-gel methods usually yield homogeneous spherical particles for pure silica or binary glasses, synthesizing poorly aggregated Cu-doped ternary glass nano/microparticles without a secondary CuO crystalline phase remains challenging. This article introduces an alternative method for fabricating Cu-doped ternary microparticles using sol-gel chemistry combined with spray-drying. The resulting microspheres exhibit well-defined, poorly aggregated particles with spherical shapes and diameters of a few microns. Copper primarily integrates into the microspheres as Cu0 nanoparticles and as Cu2+ within the amorphous network. This doping affects silica network connectivity, as calcium and phosphorus are preferentially distributed in the glass network (respectively as network modifiers and formers) or involved in amorphous calcium phosphate nano-domains depending on the doping rate. These differences affect the interaction with simulated body fluid. Network depolymerization, ion release (SiO44-, Ca2+, PO43-, Cu2+), and apatite nanocrystal layer formation are impacted, as well as copper release. The latter is mainly provided by the copper involved in the silica network and not from metal nanoparticles, most of which remain in the microspheres after interaction. This understanding holds promising implications for potential therapeutic applications, offering possibilities for both short-term and long-term delivery of a tunable copper dose. STATEMENT OF SIGNIFICANCE: A novel methodology, scalable to industrial levels, enables the synthesis of copper-doped ternary bioactive glass microparticles by combining spray-drying and sol-gel chemistry. It provides precise control over the copper percentage in microspheres. This study explores the influence of synthesis conditions on the copper environment, notably Cu0 and Cu2+ ratios, characterized by EPR spectroscopy, an aspect poorly described for copper-doped bioactive glass. Additionally, copper indirectly affects silica network connectivity and calcium/phosphorus distribution, as revealed by SSNMR. Multiscale characterization illustrates how these features impact acellular degradation in simulated body fluid, highlighting the therapeutic potential for customizable copper dosing to address short- and long-term needs.

Time-dependent change in Reishi (Ganoderma lingzhi) triterpenoids in culture with rumen fluid.

The purpose of this study was to investigate the time-dependent change in Reishi (Ganoderma lingzhi) triterpenoids in rumen fluid. G. lingzhi fruiting bodies were milled and incubated in a tube with rumen fluid for 0, 4, 8, 12, 24, and 48 h at 39°C. After incubation, all the tubes were freeze-dried and extracted by ethanol. The contents of 18 triterpenoids in the ethanol extract were quantitated by liquid chromatography-mass spectrometry (LC-MS/MS). Based on the results, triterpenoids were categorized into three groups: (1) rapid decrease, indicating reductions of more than 50% within 8 h; (2) mild decrease, with reductions of more than 50% within 48 h; and (3) minimal change, even after 48 h, there was not much change. Ganoderic acid C6, DM, H, K, and TR as well as Ganoderenic acid D were classified in (1); Ganoderic acid LM2 and T-Q as well as Ganoderiol F in (2); and Ganoderic acid A, B, C1, C2, I, and TN; Gnoderenic acid C; and Ganodermanontriol in (3). In addition, a relationship between chemical structure and metabolic speed was observed in some cases. The results of this study revealed that G. lingzhi triterpenoids are digested and metabolized at different speeds in ruminant fluid.

Potential application of body fluids autofluorescence in the non-invasive diagnosis of endometrial cancer.

BACKGROUND: Endometrial carcinoma (EC) is the most common cancer of the female reproductive tract in developed countries. The prognosis and 5-year survival rates are closely tied to the stage diagnosis. Current routine diagnostic methods of EC are either lacking specificity or are uncomfortable, invasive and painful for the patient. As of now, the gold diagnostic standard is endometrial biopsy. Early and non-invasive diagnosis of EC requires the identification of new biomarkers of disease and a screening test applicable to routine laboratory diagnostics. The application of untargeted metabolomics combined with artificial intelligence and biostatistics tools has the potential to qualitatively and quantitatively represent the metabolome, but its introduction into routine diagnostics is currently unrealistic due to the financial, time and interpretation challenges. Fluorescence spectral analysis of body fluids utilizes autofluorescence of certain metabolites to define the composition of the metabolome under physiological conditions. PURPOSE: This review highlights the potential of fluorescence spectroscopy in the early detection of EC. Data obtained by three-dimensional fluorescence spectroscopy define the quantitative and qualitative composition of the complex fluorescent metabolome and are useful for identifying biochemical metabolic changes associated with endometrial carcinogenesis. Autofluorescence of biological fluids has the prospect of providing new molecular markers of EC. By integrating machine learning and artificial intelligence algorithms in the data analysis of the fluorescent metabolome, this technique has great potential to be implemented in routine laboratory diagnostics.

Monocyte chemoattractant protein-1 detection in wound tissue fluids for the assisted diagnosis of wound infection.

BACKGROUND: Infections are commonly seen in wounds. The overall infection rate is 1.8% to 4.2%. Improper infection management can lead to serious conditions and may progress to life-threatening sepsis. Because there is a need for assistance in predicting wound infection before obvious clinical symptoms, the measurement of cytokines in wound tissue fluids has attracted our attention for determining the overall status of wound infection. Our intent was to assess the potential biomarkers in the diagnosis of wound infection. METHODS: We collected 146 tissue fluids (acute: 59, chronic: 61, and normal: 26) for analysis of biomarkers using a human cytokine array. Serum C-reactive protein was also measured from 104 patients. The sensitivity and specificity of significant wound cytokines and serum C-reactive protein for the diagnosis of wound infection were evaluated. RESULTS: Among biomarkers examined, serum C-reactive protein and tissue C-reactive protein were highly expressed in acute infection wounds, whereas monocyte chemoattractant protein-1 was significantly expressed in chronic infection wounds. Because the expression of wound biomarkers varied in different types of wounds, relationships among them were studied. A high correlation between tissue C-reactive protein and interleukin-8 (R2 = 0.7) and a moderate correlation between systemic and local C-reactive protein (R2 = 0.47) were observed. In addition, tissue monocyte chemoattractant protein-1 had better sensitivity (74%) and specificity (65%) in the diagnosis of wound infection. Moreover, combined serum C-reactive protein with monocyte chemoattractant protein-1 examination provided a higher area under the curve in the receiver operator characteristic curve (0.75). CONCLUSION: We found that tissue monocyte chemoattractant protein-1 is a superior diagnostic marker for assistance with the diagnosis of wound infection.

Uterine fluid microRNAs in repeated implantation failure.

Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive procedures, primarily because of compromised receptivity. As such, there is a need for a dependable and accurate clinical test to evaluate endometrial receptiveness, particularly during embryo transfer. MicroRNAs (miRNAs) have diverse functions in the processes of implantation and pregnancy. Dysregulation of miRNAs results in reproductive diseases such as recurrent implantation failure (RIF). The endometrium secretes several microRNAs (miRNAs) during the implantation period, which could potentially indicate whether the endometrium is suitable for in vitro fertilization (IVF). The goal of this review is to examine endometrial miRNAs as noninvasive biomarkers that successfully predict endometrium receptivity in RIF.

Decomposition of Luminescent Hydroxyapatite Scaffolds in Simulated Body Fluid.

We present a luminescence study investigating the dissolution of rare-earth-doped hydroxyapatite scaffolds in simulated body fluid (SBF), aiming to assess the luminescence stability of Tb-, Ce-, and Eu-doped scaffolds over time. Our findings reveal a consistent decrease in luminescence emission intensity across all samples over a four-week period in which the scaffolds were immersed in the SBF. In addition, energy-dispersive spectroscopy confirms a decrease in rare-earth ion concentration in the scaffolds with respect to time, whereas fluorescence spectroscopy shows the presence of rare-earth ions in the SBF, indicating the partial dissolution of the scaffolds over time. The use of rare-earth ions as luminescence markers provides insights into the mechanisms of apatite formation in hydroxyapatites. Thus, these scaffolds may find wider use in regenerative medicine, particularly in targeted drug delivery systems, where their luminescent properties have the potential to noninvasively track drug release.

Diagnosis of malignant body fluids via cancer-universal methylation in cell-free DNA.

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).

Research advances of tissue-derived extracellular vesicles in cancers.

BACKGROUND: Extracellular vesicles (EVs) can mediate cell-to-cell communication and affect various physiological and pathological processes in both parent and recipient cells. Currently, extensive research has focused on the EVs derived from cell cultures and various body fluids. However, insufficient attention has been paid to the EVs derived from tissues. Tissue EVs can reflect the microenvironment of the specific tissue and the cross-talk of communication among different cells, which can provide more accurate and comprehensive information for understanding the development and progression of diseases. METHODS: We review the state-of-the-art technologies involved in the isolation and purification of tissue EVs. Then, the latest research progress of tissue EVs in the mechanism of tumor occurrence and development is presented. And finally, the application of tissue EVs in the clinical diagnosis and treatment of cancer is anticipated. RESULTS: We evaluate the strengths and weaknesses of various tissue processing and EVs isolation methods, and subsequently analyze the significance of protein characterization in determining the purity of tissue EVs. Furthermore, we focus on outlining the importance of EVs derived from tumor and adipose tissues in tumorigenesis and development, as well as their potential applications in early tumor diagnosis, prognosis, and treatment. CONCLUSION: When isolating and characterizing tissue EVs, the most appropriate protocol needs to be specified based on the characteristics of different tissues. Tissue EVs are valuable in the diagnosis, prognosis, and treatment of tumors, and the potential risks associated with tissue EVs need to be considered as therapeutic agents.

Unobtrusive Sensors for Synchronous Monitoring of Different Breathing Parameters in Care Environments.

Respiratory problems are common amongst older people. The rapid increase in the ageing population has led to a need for developing technologies that can monitor such conditions unobtrusively. This paper presents a novel study that investigates Wi-Fi and ultra-wideband (UWB) antenna sensors to simultaneously monitor two different breathing parameters: respiratory rate, and exhaled breath. Experiments were carried out with two subjects undergoing three breathing cases in breaths per minute (BPM): (1) slow breathing (12 BPM), (2) moderate breathing (20 BPM), and (3) fast breathing (28 BPM). Respiratory rates were captured by Wi-Fi sensors, and the data were processed to extract the respiration rates and compared with a metronome that controlled the subjects' breathing. On the other hand, exhaled breath data were captured by a UWB antenna using a vector network analyser (VNA). Corresponding reflection coefficient data (S11) were obtained from the subjects at the time of exhalation and compared with S11 in free space. The exhaled breath data from the UWB antenna were compared with relative humidity, which was measured with a digital psychrometer during the breathing exercises to determine whether a correlation existed between the exhaled breath's water vapour content and recorded S11 data. Finally, captured respiratory rate and exhaled breath data from the antenna sensors were compared to determine whether a correlation existed between the two parameters. The results showed that the antenna sensors were capable of capturing both parameters simultaneously. However, it was found that the two parameters were uncorrelated and independent of one another.

HCMMD: systematic evaluation of metabolites in body fluids as liquid biopsy biomarker for human cancers.

Metabolomics is a rapidly expanding field in systems biology used to measure alterations of metabolites and identify metabolic biomarkers in response to disease processes. The discovery of metabolic biomarkers can improve early diagnosis, prognostic prediction, and therapeutic intervention for cancers. However, there are currently no databases that provide a comprehensive evaluation of the relationship between metabolites and cancer processes. In this review, we summarize reported metabolites in body fluids across pan-cancers and characterize their clinical applications in liquid biopsy. We conducted a search for metabolic biomarkers using the keywords ("metabolomics" OR "metabolite") AND "cancer" in PubMed. Of the 22,254 articles retrieved, 792 were deemed potentially relevant for further review. Ultimately, we included data from 573,300 samples and 17,083 metabolic biomarkers. We collected information on cancer types, sample size, the human metabolome database (HMDB) ID, metabolic pathway, area under the curve (AUC), sensitivity and specificity of metabolites, sample source, detection method, and clinical features were collected. Finally, we developed a user-friendly online database, the Human Cancer Metabolic Markers Database (HCMMD), which allows users to query, browse, and download metabolite information. In conclusion, HCMMD provides an important resource to assist researchers in reviewing metabolic biomarkers for diagnosis and progression of cancers.