Glycomics of cervicovaginal fluid from women at risk of preterm birth reveals immuno-regulatory epitopes that are hallmarks of cancer and viral glycosylation.

During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1ß, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women's health.

[Chinese guideline for clinical application of fluid biomarkers for Alzheimer's disease(2024 edition)].

Alzheimer's disease is the most prevalent neurodegenerative disorder leading to cognitive impairment, but its progression is subtle and the early recognition is difficult. With advancements in disease-modifying therapies, the need for precise early diagnosis of Alzheimer's disease is increasingly pressing. Fluid biomarkers of Alzheimer's disease, detectable in bodily fluid samples, are intricately associated with the disease.It can be used for screening, diagnosis, staging, prediction of disease progression, and clinical trials, playing an increasingly critical role in clinical practice.. This guideline systematically reviews and evaluates the spectrum of fluid biomarkers for Alzheimer's disease, propose standardized protocols for sample collection and processing, and delineates the application standards of fluid biomarkers in disease screening, diagnosis, staging, prognosis of disease progression, and clinical trials. A total of 24 recommendations have been formulated. The publication of this guideline aims to standardize the application of fluid biomarkers in clinical practice, thereby advancing research in Alzheimer's disease fluid biomarkers.

Self-reported exposure to blood and body fluids and serological evidence of lifetime exposure to hepatitis B virus among health care workers in Ghana: a cross-sectional study.

INTRODUCTION: In Sub-Saharan Africa alone, about 40-65% of Hepatitis B Virus infections among HCWs were a result of percutaneous occupational exposures to contaminated blood and body fluids of patients. Occupational exposure to blood and body fluids among healthcare workers is on the rise in Ghana. However, the relationship between self-reported exposures to blood and body fluids suspected to be contaminated with the hepatitis B virus and actual serological evidence of exposure remains unknown. The aim of the study however was to assess the self-reported exposure to HBV as against the serological evidence of lifetime exposure to HBV and associated factors among Ghanaian HCWs. METHODS: The study was a cross-sectional analytical survey that involved 340 HCWs who were recruited using a simple random sampling procedure from six cadres of staff from five districts in Greater Accra. The participants were surveyed using a validated instrument and 5mls of venous blood was aseptically withdrawn for qualitative detection of Anti-HBc. SPSS version 23.0 was used to analyze the data to obtain proportions, odds ratios and their corresponding confidence intervals with the level of significance set at 0.05. RESULTS: The response rate was 94% with Nurses and Doctors in the majority with a mean age of 35.6 ± 7.2. Self-reported exposure to HBV was 63% whereas lifetime exposure to HBV (Anti-HBc) prevalence was 8.2% (95% CI = 5.0-11.0%). Females were 60% less likely to be exposed to HBV (aOR = 0.4; 95% CI = 0.1-0.9) than their male counterparts. HCWs without training in the prevention of blood-borne infections had almost three times higher odds of being exposed to HBV in their lifetime (aOR = 2.6; 95% CI = 1.0-6.4). CONCLUSIONS: The findings of this study suggest that self-reported exposure to HBV-contaminated biological materials was high with a corresponding high lifetime exposure to HBV. The female gender was protective of anti-HBc acquisition. Apart from direct interventions for preventing occupational exposures to HBV in the healthcare setting, periodic training of all categories of healthcare workers in infection prevention techniques could significantly reduce exposure to the Hepatitis B virus.

Profiling of metabolic dysregulation in ovarian cancer tissues and biofluids.

Ovarian cancer (OC) is the most lethal gynecologic cancer, mainly due to late diagnosis with widespread peritoneal spread at first presentation. We performed metabolomic analyses of ovarian and paired control tissues using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to understand its metabolomic dysregulation. Of the 130 quantified metabolites, 96 metabolites of glycometabolism, including glycolysis, tricarboxylic acid cycles, urea cycles, and one-carbon metabolites, showed significant differences between the samples. To evaluate the local and systemic metabolomic differences in OC, we also analyzed low or non-invasively available biofluids, including plasma, urine, and saliva collected from patients with OC and benign gynecological diseases. All biofluids and tissue samples showed consistently elevated concentrations of N1,N12-diacetylspermine compared to controls. Four metabolites, polyamines, and betaine, were significantly and consistently elevated in both plasma and tissue samples. These data indicate that plasma metabolic dysregulation, which the most reflected by those of OC tissues. Our metabolomic profiles contribute to our understanding of metabolomic abnormalities in OC and their effects on biofluids.

Near-infrared excitation Raman spectroscopy of colored fabric contaminated with body fluids.

Confirmatory identification of dyes in the physical pieces of evidence, such as hair and fabric, is critically important in forensics. This information can be used to demonstrate the link between a person of interest and a crime scene. High performance liquid chromatography is broadly used for dye analysis. However, this technique is destructive and laborious. This problem can be overcome by near-Infrared excitation Raman spectroscopy (NIeRS), non-invasive and non-destructive technique that can be used to determine chemical structure of highly fluorescent dyes. Analyzed fabric materials often possess body fluid stains, which may obscure the accuracy of NIeRS-based identification of dyes. In this study, we investigate the extent to which fabric contamination with body fluids can alter the accuracy of NIeRS. Our results showed that NIeRS coupled with partial-least squared discriminant analysis (PLS-DA) enabled on average 97.6% accurate identification of dyes on fabric contaminated with dry blood, urine and semen. We also found that NIeRS could be used to identify blood, urine and semen on such fabric with 99.4% accuracy. Furthermore, NIeRS could be used to differentiate between wet and dry blood, as well as reveal the presence of blood on washed fabric. These results indicate that NIeRS coupled with PLS-DA could be used as a robust and reliable analytical approach in forensic analysis of fabric.

An Inflection Point in High-Throughput Proteomics with Orbitrap Astral: Analysis of Biofluids, Cells, and Tissues.

This Technical Note presents a comprehensive proteomics workflow for the new combination of Orbitrap and Astral mass analyzers across biofluids, cells, and tissues. Central to our workflow is the integration of Adaptive Focused Acoustics (AFA) technology for cells and tissue lysis to ensure robust and reproducible sample preparation in a high-throughput manner. Furthermore, we automated the detergent-compatible single-pot, solid-phase-enhanced sample Preparation (SP3) method for protein digestion. The synergy of these advanced methodologies facilitates a robust and high-throughput approach for cell and tissue analysis, an important consideration in translational research. This work disseminates our platform workflow, analyzes the effectiveness, demonstrates the reproducibility of the results, and highlights the potential of these technologies in biomarker discovery and disease pathology. For cells and tissues (heart, liver, lung, and intestine) proteomics analysis by data-independent acquisition mode, identifications exceeding 10,000 proteins can be achieved with a 24 min active gradient. In 200 ng injections of HeLa digest across multiple gradients, an average of more than 80% of proteins have a CV less than 20%, and a 45 min run covers ∼90% of the expressed proteome. This complete workflow allows for large swaths of the proteome to be identified and is compatible with diverse sample types.

Recent progress on media for biological sample preparation.

The analysis of biological samples is highly valuable for disease diagnosis and treatment, forensic examination, and public safety. However, the serious matrix interference effect generated by biological samples severely affects the analysis of trace analytes. Sample preparation methods are introduced to address the limitation by extracting, separating, enriching, purifying trace target analytes from biological samples. With the raising demand of biological sample analysis, a review focuses on media for biological sample preparation and analysis over the last 5 years is presented. High-performance media in biological sample preparation are first reviewed, including porous organic frameworks, imprinted polymers, hydrogels, ionic liquids, and bioactive media. Then, application of media for different biological sample preparation and analysis is briefly introduced, including liquid samples of body fluids, solid samples (hair, feces, and tissues), and gas samples of exhale breath gas. Finally, conclusions and outlooks on media promoting biological sample preparation are presented.

Millimeter-scale soft capsules for sampling liquids in fluid-filled confined spaces.

Sampling liquids in small and confined spaces to retrieve chemicals and microbiomes could enable minimally invasive monitoring human physiological conditions for understanding disease development and allowing early screening. However, existing tools are either invasive or too large for sampling liquids in tortuous and narrow spaces. Here we report a fundamental liquid sampling mechanism that enables millimeter-scale soft capsules for sampling liquids in confined spaces. The miniature capsule is enabled by flexible magnetic valves and superabsorbent polymer, fully wirelessly controlled for on-demand fluid sampling. A group of miniature capsules could navigate in fluid-filled and confined spaces safely using a rolling locomotion. The integration of on-demand triggering, sampling, and sealing mechanism and the agile group locomotion allows us to demonstrate precise control of the soft capsules, navigating and sampling body fluids in a phantom and animal organ ex vivo, guided by ultrasound and x-ray medical imaging. The proposed mechanism and wirelessly controlled devices spur the next-generation technologies for minimally invasive disease diagnosis.

Comprehensive body fluid identification and contributor assignment by combining targeted sequencing of mRNA and coding region SNPs.

Forensic genetic analyses aim to retrieve as much information as possible from biological trace material recovered from crime scenes. While standard short tandem repeat (STR) profiling is essential to individualize biological traces, its significance is diminished in crime scenarios where the presence of a suspect's DNA is acknowledged by all parties. In such cases, forensic (m)RNA analysis can provide crucial contextualizing information on the source level about a trace's composition, i.e., body fluids/tissues, and has therefore emerged as a powerful tool for modern forensic investigations. However, the question which of several suspects contributed a specific component (body fluid) to a mixed trace cannot be answered by RNA analysis using conventional methods. This individualizing information is stored within the sequence of the mRNA transcripts. Massively parallel sequencing (MPS) represents a promising alternative, offering not only higher multiplex capacity, but also the typing of individual coding region SNPs (cSNPs) to enable the assignment of contributors to mixture components, thereby reducing the risk of association fallacies. Herein, we describe the development of an extensive mRNA/cSNP panel for targeted sequencing on the IonTorrent S5 platform. Our panel comprises 30 markers for the detection of six body fluids/tissues (blood, saliva, semen, skin, vaginal and menstrual secretion), along with 70 linkage-controlled cSNPs for contributor assignment. It exhibited high reliable detection sensitivity with RNA inputs down to 0.75 ng and a conservatively calculated probability of identity of 0.03 - 6 % for individual body fluid-specific cSNP profiles. Limitations and areas for future work include RNA-related allele imbalances, inclusion of markers to correctly identify rectal mucosa and the optimization of specific markers. In summary, our new panel is intended to be a major step forward to interpret biological evidence at sub-source and source level based on cSNP attribution of a body fluid component to a suspect and victim, respectively.

Opportunities and Drawbacks of Digitalized Morphologic Analysis of Body Fluids.

Body fluid analysis has become a critical component of diagnostic and clinical decision-making for a wide spectrum of human pathologies. An automated microscope, a high-quality digital camera, and a software designed to identify and automatically preclassify cells and other features in stained smears comprise the most recent generation of digital morphologic analyzers. The time necessary for expert operator reclassification is another aspect that must be considered at this stage of development, because identifying and sorting distinct elements in body fluids still necessitates the involvement of an expert morphologist.

Calcium Citrate Amount and Gelatine Source Impact on Hydroxyapatite Formation in Bone Regeneration Material in Simulated Body Fluid.

Bone grafting is crucial for bone regeneration. Recent studies have proposed the use of calcium citrate (CC) as a potential graft material. Notably, citrate does not inhibit hydroxyapatite (HAp) formation at specific calcium-to-citrate molar ratios. Octacalcium phosphate (OCP)/gelatine (Gel) composites, which are commonly produced from porcine Gel, are valued for their biodegradability and bone replacement capability. This study introduces fish Gel as an alternative to porcine Gel because of its wide acceptance and eco-friendliness. This is the first study to examine the interaction effects between two osteogenic materials, OCP/CC, and the influence of different gelatine matrix components on HAp formation in an SBF. Samples with varying CC contents were immersed in an SBF for 7 d and analysed using various techniques, confirming that high CC doses prevent HAp formation, whereas lower doses facilitate it. Notably, small-sized OCP/CC/porcine Gel composites exhibit a high HAp generation rate. Porcine Gel composites form denser HAp clusters, whereas fish Gel composites form larger spherical HAps. This suggests that lower CC doses not only avoid inhibiting HAp formation but also enhance it with the OCP/Gel composite. Compared with porcine Gel, fish Gel composites show less nucleation but an increased crystal growth for HAp.

Characterization of vaginal Lactobacillus in biologically relevant fluid using surface-enhanced Raman spectroscopy.

The native vaginal microbiome plays a crucial role in maintaining vaginal health and disruption can have significant consequences for women during their lifetime. While the composition of the vaginal microbiome is important, current methods for monitoring this community are lacking. Clinically used techniques routinely rely on subjective analysis of vaginal fluid characteristics or time-consuming microorganism culturing. Surface-enhanced Raman spectroscopy (SERS) can aid in filling this gap in timely detection of alterations in the vaginal microbiome as it can discriminate between bacterial species in complex solutions including bacterial mixtures and biofluids. SERS has not previously been applied to study variations in vaginal Lactobacillus, the most common species found in the vaginal microbiome, in complex solutions. Herein, the SERS spectra of Lactobacillus crispatus (L. crispatus) and Lactobacillus iners (L. iners), two of the most common vaginal bacteria, was characterized at physiologically relevant concentrations. Subsequently, the ability of SERS to detect L. crispatus and L. iners in both pure mixtures and when mixed with a synthetic vaginal fluid mimicking solution was determined. In both pure and complex solutions, SERS coupled with partial least squares regression predicted the ratiometric bacterial content with less than 10% error and strong goodness of prediction (Q2 > 0.9). This developed method highlights the applicability of SERS to predict the dominant Lactobacillus in the vaginal micro-environment toward the monitoring of this community.

Concentration of Marbofloxacin in equine subcutaneous tissue fluid after subcutaneous administration in encapsulated microparticles.

Surgical-site infections (SSIs) at implant sites in horses are sometimes difficult to control with systemic antimicrobials. Because one of the likely reasons is insufficient antimicrobial concentrations, there is a need to increase these concentrations in and around the infected tissue. Marbofloxacin (MAR)-encapsulated microparticles (MAR-MPs) made of biodegradable poly (lactic-co-glycolic) acid are capable of sustained release in vitro. We examined the concentration of MAR in the subcutaneous tissue fluid at sites where MAR-MPs had been administered. On day 0, six 3- × 4-cm subcutaneous pockets were created in the neck of each of six Thoroughbred horses under sedation and local anesthesia. MAR-MPs containing 50 mg of MAR were added to each pocket, which was then sutured. On days 1, 2, 3, 4, and 7, subcutaneous tissue fluid from one pocket per horse was collected and analyzed by LC-MS/MS. From days 1 to 7, the median MAR concentration in the subcutaneous tissue fluid ranged from 17.7 (4.89-125.6) to 33.05 (15.1-71.6) µg/mL. The median concentrations in the subcutaneous tissue fluid exceeded the MIC90 (the minimum inhibitory concentration that would inhibit the growth of 90 % of the tested bacterial isolates) of MAR for clinical isolates reported previously. The area of swelling at the site of administration was significantly larger on days 1 to 4 than just after administration (P < 0.05). MAR-MPs could be useful for controlling SSIs that require high antimicrobial concentrations for extended periods when they are used with strategies that reduce side effects.

Biomarkers in Alzheimer's disease.

Alzheimer's disease (AD) is among the most common neurodegenerative disorders. AD is characterized by deposition of neurofibrillary tangles and amyloid plaques, leading to associated secondary pathologies, progressive neurodegeneration, and eventually death. Currently used diagnostics are largely image-based, lack accuracy and do not detect early disease, ie, prior to onset of symptoms, thus limiting treatment options and outcomes. Although biomarkers such as amyloid-ß and tau protein in cerebrospinal fluid have gained much attention, these are generally limited to disease progression. Unfortunately, identification of biomarkers for early and accurate diagnosis remains a challenge. As such, body fluids such as sweat, serum, saliva, mucosa, tears, and urine are under investigation as alternative sources for biomarkers that can aid in early disease detection. This review focuses on biomarkers identified through proteomics in various biofluids and their potential for early and accurate diagnosis of AD.

Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.

Lipid metabolites abnormally expressed in pelvic fluid as potential biomarkers for ovarian cancer: A case-control study.

BACKGROUND: Ovarian cancer is insidious and usually detected in advanced stages of the disease. As the ovaries are pelvic organs, changes in their pelvic fluid metabolites may be associated with ovarian cancer. METHODS: Metabolomic changes in the pelvic fluid were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with ovarian cancer, ovarian cysts and uterine fibroids. Area under the curve (AUC) analysis was used to assess the diagnostic performance of lipid metabolites and blood tumor indices. The Pearson correlation algorithm was used to analyze the correlation between clinical characteristics and lipid metabolites in ovarian cancer patients. RESULTS: There were 24 lipid metabolites significantly changed in the pelvic fluid of ovarian cancer patients (p < 0.05). Palmitoylcarnitine, lipoamide, lipid metabolites, and blood tumor indices (CA15-3 and CA125) showed AUC > 0.8, with palmitoylcarnitine reaching a high of 0.942. In addition, we found that some lipid metabolites were significantly associated with the clinical stage, abdominal water volume, lymphatic metastasis, and recurrence (p < 0.05, r > 0.5). CONCLUSION: Levels of specific lipid metabolites are potential biomarkers of ovarian cancer and may play a key role in the early diagnosis and prognostic assessment of ovarian cancer. SIGNIFICANCE: Our results showed that pelvic metabolites, especially some lipid metabolites, play an important role in the diagnosis of ovarian cancer. Meanwhile, partial lipid metabolites were closely associated with the clinical presentation and prognosis of patients with ovarian cancer. We believe that our study makes a significant contribution to the literature because it provides a potential approach that is more effective for ovarian cancer detection.

Degradation Behavior of Medical MgZZC-1 in Various Simulated Body Fluids.

Magnesium-based biodegradable metal bone implants exhibit superior mechanical properties compared to biodegradable polymers for orthopedic and cardiovascular stents. In this study, MgZZC-x (x = 1, 1.2) alloys were screened by in vitro biocompatibility tests in three simulated body fluids under nontoxic conditions. The MgZZC-1 alloys with better biocompatibility were selected to predict the days required for complete degradation. The evolution of degradation products was analyzed, and the mechanism of formation of the product film was inferred. A degradation kinetic model was established to investigate the effect of MEM components on the degradation of the alloys. The results demonstrate that the proteins in MEM can greatly retard the degradation progress by attaching to the surface of MgZZC-1 alloys, which are predicted to degrade completely within 341 days. The carbonate and phosphate buffers were adjusted to pH in MEM solution, delaying the degradation of magnesium alloys. This process in MEM more accurately reflects the actual degradation in the body and is superior to that in Hanks and SBF solutions. This study will promote the application of biodegradable materials in clinical medicine.

Nanozyme-Catalyzed Colorimetric Detection of the Total Antioxidant Capacity in Body Fluids by Paper-Based Microfluidic Chips.

Total antioxidants play a crucial role in human health, and detection of the total antioxidant capacity (TAC) has broad application prospects in fields such as food safety, environmental assessment, and disease diagnosis. However, a long detection time, cumbersome steps, high cost, reliance on professional equipment, and nonportability still remain significant challenges. In this work, an efficient strategy of point-of-care testing (POCT) of the TAC in body fluids by nanozyme-catalyzed colorimetric paper-based microfluidic sensors is proposed. The paper-based microfluidic sensors coupled with a smartphone can reduce testing costs and provide portability. The nanozyme prepared by the solvothermal method presents Michaelis constants of 0.11 and 0.129 mM for H2O2 and TMB, respectively. A method for immobilizing nanozymes and chromogenic agents on a paper-based microfluidic chip is established. Based on smartphone photography and image grayscale extraction, the TAC can be qualitatively detected with a detection limit and linear range of 33.4 and 50-700 µM, respectively. Furthermore, the proposed sensor can realize the one-step quantitative analysis of the TAC in body fluids (blood, saliva, and sweat) within 15 min. The proposed nanozyme-catalyzed colorimetric paper-based microfluidic sensors presented in this study exhibit promising application prospects in the fields of biochemical analysis and POCT.

The glycosylation landscape of prostate cancer tissues and biofluids.

An overview of the role of glycosylation in prostate cancer (PCa) development and progression is presented, focusing on recent advancements in defining the N-glycome through glycomic profiling and glycoproteomic methodologies. Glycosylation is a common post-translational modification typified by oligosaccharides attached N-linked to asparagine or O-linked to serine or threonine on carrier proteins. These attached sugars have crucial roles in protein folding and cellular recognition processes, such that altered glycosylation is a hallmark of cancer pathogenesis and progression. In the past decade, advancements in N-glycan profiling workflows using Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) technology have been applied to define the spatial distribution of glycans in PCa tissues. Multiple studies applying N-glycan MALDI-MSI to pathology-defined PCa tissues have identified significant alterations in N-glycan profiles associated with PCa progression. N-glycan compositions progressively increase in number, and structural complexity due to increased fucosylation and sialylation. Additionally, significant progress has been made in defining the glycan and glycopeptide compositions of prostatic-derived glycoproteins like prostate-specific antigen in tissues and biofluids. The glycosyltransferases involved in these changes are potential drug targets for PCa, and new approaches in this area are summarized. These advancements will be discussed in the context of the further development of clinical diagnostics and therapeutics targeting glycans and glycoproteins associated with PCa progression. Integration of large scale spatial glycomic data for PCa with other spatial-omic methodologies is now feasible at the tissue and single-cell levels.

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.