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Background: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application., Objective: Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment., Design: As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach., Methods: We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs., Results: We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively., Conclusion: In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

In the bloodstream or other physiological fluids, "circulating cells and sub-cellular bio-particles" include many microscopic biological elements such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, microRNAs, platelets, immune cells, and proteins are the most well-known and investigated. These structures are crucial biomarkers in healthcare and medical research for the early detection of cancer and other disorders, enabling treatment to commence before the onset of clinical symptoms and enhancing the efficacy of treatments. As the size of these biomarkers to be detected decreases and their numbers in body fluids diminishes, the detection materials, ranging from visual inspection to advanced microscopy techniques, begin to become smaller, more sensitive, faster, and more effective, thanks to developing nanotechnology. This review first defines the circulating cells and subcellular bio-particles with their biological, physical, and mechanical properties and second focuses on their diagnostic importance, including their most recent applications as biomarkers, the biosensors that are utilized to detect them, the present obstacles that must be surmounted, and prospective developments in the domain. As technology advances and biomolecular pathways are deepens, diagnostic tests will become more sensitive, specific, and thorough. Finally, integrating recent advances in the diagnostic use of circulating cells and bioparticles into clinical practice is promising for precision medicine and patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

African swine fever (ASF) is one of the deadliest swine diseases, causing significant economic losses, threatening food security, and limiting pig production in affected countries. In the absence of an effective ASF vaccine, prevention and control of ASF depend mainly on effective biosecurity measures. In this study, the efficacy of SAFER ® , a powdered disinfectant containing clay, an acid complex, and the active ingredient thyme essential oil, was tested against the ASF virus. The results showed that ASFV isolate (VNUA/HY/ASF1/Vietnam/2019) was inactivated by 3.5 and 5 Log 10 HAD 50 /ml after 20 and 120 min of treatment with SAFER ® , respectively. When body fluids contaminated with ASFV, such as blood, saliva, urine, and feces, were treated with SAFER ® for 20 min, the ASFV titer was reduced by 1.6, 2.2, 2.0, and 2.2 Log 10 HAD 50 /ml, respectively., Competing Interests: EL, MM-M, LP, AM, A-CD, and PC were employed by Olmix SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Trinh, Lazenec, Lai, Matard-Mann, Phat, Morvan, Delahaye, Collén, Nguyen and Le.)

A rapid, straightforward, and sensitive approach to quantifying enantiomeric barbiturates in serum was developed by integrating ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) with large-volume sample stacking (LVSS) in capillary electrophoresis (CE). UA-DLLME was employed for sample preparation, and on-column preconcentration by using LVSS with polarity switching was implemented to enhance sensitivity. We thoroughly investigated and optimized various parameters influencing extraction and stacking to achieve optimal detection performance with the highest enrichment efficiencies. Under optimal extraction conditions (injection of a mixed solution containing 40 μL of CHCl 3 and 200 μL of tetrahydrofuran into 1 mL of a sample solution at pH 10.0), LVSS was performed using 600 mM Tris-boric acid (pH 9.5) containing 35 mM hydroxypropyl-β-cyclodextrin and sodium taurodeoxycholate hydrate. A voltage of 20 kV was applied and a preinjection water plug was loaded at a height of 25 cm for 10 s. Subsequently, the sample solution was injected at a height of 25 cm for 480 s, after which a voltage of -20 kV was applied and the sample stacking was initiated. The stacking process was completed when 95 % of the separation current was attained. Under optimized conditions, the contraction folds of the four barbiturate analytes (R, S-Secobarbital, R, S-pentobarbital) were improved by approximately 6400-fold, achieving detection limits of 0.1 ng/mL. The limits of quantification for all analyte enantiomers were 0.5-50 ng/mL, demonstrating good linearity (r > 0.997). Migration times exhibited a relative standard deviation of less than 1.7 %, whereas peak areas for the four analytes exhibited a deviation of 8.7 %. Finally, the established method was effectively applied to the analysis of human serum samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 (K D ), 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Arterial thrombosis contributes to some of the most frequent causes of mortality globally, such as myocardial infarction and stroke. Platelets are essential mediators of physiological haemostasis and pathological thrombosis. Platelet activation is controlled by a multitude of signalling pathways. Upon activation, platelets shed platelet-derived extracellular vesicles (pEVs). In this Special Issue: Extracellular Vesicles, Moon et al. investigate the impact of various platelet agonists (thrombin, ADP, collagen) on the proteome of pEVs. The study demonstrates that pEVs exhibit an agonist-dependent altered proteome compared to their parent cells, with significant variations in proteins related to coagulation, complement, and platelet activation. The study observes the rapid generation of pEVs following agonist stimulation with specific proteome alterations that underscore an active packaging process. This commentary highlights the implications of their findings and discusses the role of pEV cargo in cardiovascular disease with potential novel therapeutic and diagnostic opportunities., (© 2024 The Author(s). PROTEOMICS published by Wiley‐VCH GmbH.)

Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.

The present study aimed to identify novel biostimulatory compounds in boar seminal gel (SG), saliva and semen using Gas chromatography-mass spectrometry (GC-MS). The bio-stimulatory effect of SG, SG + saliva and SG + semen on young boar for semen collection as well were employed to study bio-stimulatory effects on gilts and sows. Distilled water (DW) exposure was kept as control. SG, saliva and semen were screened for total 105, 96 and 89 compounds. The highest concentration was of alkanes followed by sugar alcohols, then hydrocarbons, amino acids and fatty acids. Elaidic acid was the novel compound identified in pigs. Significantly higher ( p  < 0.05) number of males got trained in exposure to SG (80%), SG + saliva (75%) and SG + semen (75%) than control (0%). The time (hrs) taken by young boars to get trained on exposure to combination of SG + saliva (244 ± 22.19) and SG + semen (216 ± 13.14) was lesser ( p  < 0.05) than SG (356 ± 61.85) alone. Interval (hrs) from initiation of exposure for exhibition of different sexual behaviour by males on exposure to SG, saliva and semen was lesser ( p  < 0.05) than control. Significantly ( p  < 0.05) higher number of females showed estrus response to exposure of SG (72.72%), SG + saliva (69.23%) and SG + semen (76.92%) than control (0). Interval (hrs) taken to exhibit estrus was shorter ( p  < 0.05) in females exposed to SG + saliva (201.88 ± 12.66), SG + semen (198.20 ± 9.42) than SG (262.14 ± 20.06) alone. Interval (hrs) for exhibition of different sexual behaviour by females on exposure to SG + saliva and SG + semen was lesser ( p  < 0.05) than control. In conclusion, novel compounds were identified in boar seminal gel, saliva and semen with biostimulatory properties have been identified in boar SG, saliva and semen. The combined exposure of SG with saliva and semen has more intense biostimulation effect than SG alone for training of young boars and estrus induction in gilts and sows. Such compounds biostimulatory effects can be exploited for augmenting reproductive efficiency in pigs.

Peptides carry important functions in normal physiological and pathophysiological processes and can serve as clinically useful biomarkers. Given the ability to diffuse passively across endothelial barriers, endogenous peptides can be examined in several body fluids, including among others urine, blood, and cerebrospinal fluid. This review article provides an update on the recently published literature that reports on investigating native peptides in body fluids using mass spectrometry-based platforms, specifically those studies that focus on the application of peptides as biomarkers to improve clinical management. We emphasize on the critical evaluation of their clinical value, how close they are to implementation, and the associated challenges and potential solutions to facilitate clinical implementation. During the last 5 years, numerous studies have been published, demonstrating the increased interest in mass spectrometry for the assessment of endogenous peptides as potential biomarkers. Importantly, the presence of few successful examples of implementation in patients' management and/or in the context of clinical trials indicates that the peptide biomarker field is evolving. Nevertheless, most studies still report evidence based on small sample size, while validation phases are frequently missing. Therefore, a gap between discovery and implementation still exists., (© 2023 John Wiley & Sons Ltd.)

Background: Most modern haematology analysers have a dedicated body fluid mode for cell counts of body fluids. Many analysers also count the number of high fluorescence cells (HF cells). HF cells have a large nuclear size and emit high fluorescence when stained with fluorescent dyes. Due to their large nuclear size, Malignant cells are counted as HF cells., Aims and Objectives: We aim to determine the diagnostic utility of HF cells in predicting the presence of malignant cells in serous effusions., Materials and Methods: HF cell counts were done on 209 serous fluid samples using the body fluid mode of Mindray BC-6800 plus haematology analyser. Papanicilaou-stained smears of all samples were examined for the presence of malignant cells by a panel of cytopathologists. ROC curve analysis was done to determine the sensitivity and specificity of HF cells in malignant effusions., Results: Out of 209 samples, malignant cells were found by microscopy in 97 cases (46.4%). The absolute number and percentage of HF cells were significantly higher ( P < 0.001) in malignant effusions (HF# = 24.9 cells/ul, HF% = 10.4%) when compared to non-malignant samples (HF# = 4.95 cells/ul, HF% = 5.76%). ROC curve analysis determined an optimal cut-off of ≥30 HF cells/ul (sensitivity = 73.91, specificity = 55.66%) for the prediction of malignant cells., Conclusion: HF cells in serous effusions can be a helpful tool to aid the pathologist, but it is not an ideal screening test due to its low sensitivity (67.74%) and negative likelihood ratio (0.5) at a cut-off of ≥30 HF cells/ul. However, due to high specificity of 83.18% at a cut-off of ≥72 HF cells/ul, a meticulous search for malignant cells should be done on microscopy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Cytology | Indian Academy of Cytologists.)

Objective: To determine if oral secretions (OS) can be used as a noninvasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks., Study Design: This was a retrospective, single center cohort study that included data and convenience samples from week-of-life (WoL) 3 from 2 independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatal Intensive Care Unit (NICU) (Cohort 1; n = 23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; n = 17 infants including 8 with BPD)., Results: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS., Conclusions: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization and timely tailored treatment of at-risk infants with novel therapies., Competing Interests: Declaration of Competing Interest CRM receives research funding from Mead Johnson Nutrition and serves on the advisory boards of Lactalogics, Plakous Therapeutics, and Vitara Biomedical. None of these relationships have a direct conflict with this study. All other authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The surface properties of cardiovascular biomaterials play a critical role in their biological responses. Although bacterial nanocellulose (BNC) materials have exhibited potential applications in cardiovascular implants, the impact of their surface characteristics on biocompatibility has rarely been studied. This study investigated the mechanism for the biocompatibility induced by the physicochemical properties of both sides of BNC. With greater wettability and smoothness, the upper BNC surface reduced protein adsorption by 25 % compared with the lower surface. This prolonged the plasma re-calcification time by 14 % in venous blood. Further, compared with the lower BNC surface, the upper BNC surface prolonged the activated partial thromboplastin time by 5 % and 4 % in arterial and venous blood, respectively. Moreover, the lower BNC surface with lesser rigidity, higher roughness, and sparser fiber structure promoted cell adhesion. The lower BNC surface enhanced the proliferation rate of L929 and HUVECs cells by 15 % and 13 %, respectively, compared with the upper BNC surface. With lesser stiffness, the lower BNC surface upregulated the expressions of CD31 and eNOS while down-regulating the ICAM-1 expression - This promoted the proliferation of HUVECs. The findings of this study will provide valuable insights into the design of blood contact materials and cardiovascular implants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

Reflective writing develops meta-cognition among students. Therefore, it is of interest to compare effectiveness of post lecture reflective writing to didactic lecture between individual and group reflective writing. Hence, we included 124 first-year students from AIIMS Bhopal, India and divided them in two groups of 62 students. Both groups took a pre-test using a reflection questionnaire. Students were taught reflective writing. Both groups attended physiology lectures on two different topics. First lecture on body fluids where Group A wrote reflections individually and Group B did so in sub-groups (B1 to B6). After another lecture on Pathophysiology of oedema, Group A wrote reflections in groups and Group B wrote individually (A1 to A6). Both groups took a test in the form of MCQ about reflective writing on lectures. After intervention both groups took a post-test using a reflection questionnaire. Mean and standard deviation of Pre-test is 3.86 ± 0.86 and Post-test is 7.58 ± 1.01, respectively. The Mean and standard deviation of reflection who wrote individually is 38.05 ± 4.41 and in group is 27.45 ± 3.93, respectively with p-value < 0.05. Evaluation of students who wrote reflection in groups after second lecture the mean and standard deviation of reflection who wrote individually is 38.22 ± 4.64 and in group is 27.03 ± 2.87 respectively with p-value < 0.05. The performance of students who wrote reflection in groups is not satisfactory as compared to students who wrote their reflection individually., (© 2024 Biomedical Informatics.)

Linaprazan (AZD0865, TX07) is one of potassium-competitive acid blockers. However, linaprazan is rapidly excreted from the body, shortening its acid inhibition property. Linaprazan glurate (X842) is a prodrug of linaprazan with a prolonged inhibitory effect on gastric acid secretion. Linaprazan glurate has entered clinical trials, but few studies have reported its metabolism in non-clinical and clinical settings. In this study, we studied the pharmacokinetics, tissue distribution, mass balance, and metabolism of linaprazan glurate in rats after a single oral dose of 2.4 mg/kg (100 µCi/kg) [ 14 C]linaprazan glurate. The results demonstrated that linaprazan glurate was mainly excreted via feces in rats with 70.48% of the dose over 168 h. The plasma AUC 0 - ∞ of linaprazan glurate in female rats was 2 times higher than that in male rats. Drug-related substances were mainly concentrated in the stomach, eyes, liver, small intestine, and large intestine after administration. In blood, drug-related substances were mostly distributed into plasma instead of hemocytes. In total, 13 metabolites were detected in rat plasma, urine, feces, and bile. M150 (2,6-dimethylbenzoic acid) was the predominant metabolite in plasma, accounting for 80.65% and 67.65% of AUC 0-24 h in male and female rats, respectively. Based on the structures, linaprazan glurate was mainly hydrolyzed into linaprazan, followed by a series of oxidation, dehydrogenation, and glucuronidation in rats. Besides, CES2 is the main metabolic enzyme involved in the hydrolysis of linaprazan glurate to linaprazan., Competing Interests: Declaration of Competing Interest Authors PSH, ML and JX were employed by Jiangsu Sinorda Biomedicine Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Advancements in research concerning the occurrence of microplastics (MPs) in human blood, sputum, urine, and breast milk samples have piqued the interest of the scientific community, prompting further investigation. MPs present in the placenta, amniotic fluid, and meconium raise concerns about interference with embryonic development, leading to preeclampsia, stillbirth, preterm birth, and spontaneous abortion. The challenges posed by MPs extend beyond pregnancy, affecting the digestive, reproductive, circulatory, immune, and central nervous systems. This has spurred scientists to examine the origins of MPs in distinct environmental layers, including air, water, and soil. These risks continue after birth, as neonates are continuously exposed to MPs through everyday items such as breast milk, cow milk and infant milk powder, as well as plastic-based products like feeding bottles and breast milk storage bags. It is the need of the hour to strike a balance amidst lifestyle changes, alternative choices to traditional plastic products, raising awareness about plastic-related health risks, and fostering collaboration between the scientific community and policymakers. This review aims to provide fresh insights into potential sources of MP pollution, with a specific focus on pregnancy and neonates. It is the first compilation of its kind so far that includes critical studies on recently reported discoveries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be inherited or accumulated throughout a lifetime and be reversible, prompting investigation of their use across various fields. In forensic sciences, multiple applications have been proposed, such as the discrimination of monozygotic twins, identifying the source of a biological trace left at a crime scene, age prediction, determination of body fluids and tissues, human behavior association, wound healing progression, and determination of the post-mortem interval (PMI). Despite all these applications, not all the studies considered the impact of PMI and post-sampling effects on the epigenetic modifications and the tissue-specificity of the epigenetic marks.This review aims to highlight the substantial forensic significance that epigenetics could support in various forensic investigations. First, basic concepts in epigenetics, describing the main epigenetic modifications and their functions, in particular, DNA methylation, histone modifications, and non-coding RNA, with a particular focus on forensic applications, were covered. For each epigenetic marker, post-mortem stability and tissue-specificity, factors that should be carefully considered in the study of epigenetic biomarkers in the forensic context, have been discussed. The advantages and limitations of using post-mortem tissues have been also addressed, proposing directions for these innovative strategies to analyze forensic specimens., (© 2024. The Author(s).)

The microbiome of saliva stains deposited at crime scenes and in everyday settings is valuable for forensic investigations and environmental ecology. However, the dynamics and applications of microbial communities in these saliva stains have not been fully explored. In this study, we analyzed saliva samples that were exposed to indoor conditions for up to 1 year and to different carriers (cotton, sterile absorbent cotton swab, woolen, dacron) in both indoor and outdoor environments for 1 month using high-throughput sequencing. The analysis of microbial composition and Mfuzz clustering showed that the salivary flora, specifically Streptococcus (cluster7), which was associated with microbial contamination, remained stable over short periods of time. However, prolonged exposure led to significant differences due to the invasion of environmental bacteria such as Pseudomonas and Achromobacter. The growth and colonization of environmental flora were promoted by humidity. The neutral model predictions indicated that the assembly of salivary microbial communities in outdoor environments was significantly influenced by stochastic processes, with environmental characteristics having a greater impact on community change compared to surface characteristics. By incorporating data from previous studies on fecal and vaginal secretion microbiology, we developed RF and XGBoost classification models that achieved high accuracy (>98 %) and AUC (>0.8). Additionally, a RF regression model was created to determine the time since deposition (TsD) of the stains. Time inference models yielded a mean absolute error (MAE) of 7.1 days for stains exposed for 1 year and 14.2 h for stains exposed for 14 days. These findings enhance our understanding of the changes in the microbiome of saliva stains over time, in different environments, and on different surfaces. They also have potential applications in assessing potential microbial contamination, identifying body fluids, and inferring the time of deposition., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

RNAs have attracted much attention in forensic body fluid/tissue identification (BFID) due to their tissue-specific expression characteristics. Among RNAs, long RNAs (e.g., mRNA) have a higher probability of containing more polymorphic sites that can be used to assign the specific donor of the body fluid/tissue. However, few studies have characterized their overall profiles in forensic science. In this study, we sequenced the transcriptomes of 30 samples from venous blood, menstrual blood, semen, saliva, vaginal secretion, and skin tissue, obtaining a comprehensive picture of mRNA, lncRNA, and circRNA profiles. A total of 90,305 mRNAs, 102,906 lncRNAs (including 19,549 novel lncRNAs), and 40,204 circRNAs were detected. RNA type distribution, length distribution, and expression distribution were presented according to their annotation and expression level, and many novel body fluid/tissue-specific RNA markers were identified. Furthermore, the cognate relations among the three RNAs were analyzed according to gene annotations. Finally, SNPs and InDels from RNA transcripts were genotyped, and 21,611 multi-SNP and 4,471 multi-InDel transcriptomic microhaplotypes (tMHs) were identified. These results provide a comprehensive understanding of transcriptome profiles, which could provide new avenues for tracing the origin of the body fluid/tissue and identifying an individual., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Persistent, mobile and toxic substances have drawn attention nowadays due to their particular properties, but they are overlooked in human monitorization works, limiting the knowledge of the human exposome. In that sense, human urine is an interesting matrix since not only parent compounds are eliminated, but also their phase II metabolites that could act as biomarkers. In this work, 11 sample preparation procedures involving preconcentration were tested to ensure maximum analytical coverage in human urine using mixed-mode liquid chromatography coupled with high-resolution tandem mass spectrometry. The optimized procedure consisted of a combination of solid-phase extraction and salt-assisted liquid-liquid extraction and it was employed for suspect screening. Additionally, a non-discriminatory dilute-and-shoot approach was also evaluated. After evaluating the workflow in terms of limits of identification and type II errors (i.e., false negatives), a pooled urine sample was analysed. From a list of 1450 suspects and in-silico simulated 1568 phase II metabolites (i.e. sulphates, glucuronides, and glycines), 44 and 14 substances were annotated, respectively. Most of the screened suspects were diverse industrial chemicals, but biocides, natural products and pharmaceuticals were also detected. Lastly, the complementarity of the sample preparation procedures, columns, and analysis conditions was assessed. As a result, dilute-and-shoot and the Acclaim Trinity P1 column at pH = 3 (positive ionization) and pH = 7 (negative ionization) allowed the maximum coverage since almost 70 % of the total suspects could be screened using those conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Blood-containing mixtures are frequently encountered at crime scenes involving violence and murder. However, the presence of blood, and the association of blood with a specific donor within these mixtures present significant challenges in forensic analysis. In light of these challenges, this study sought to address these issues by leveraging blood-specific methylation sites and closely linked microhaplotype sites, proposing a novel composite genetic marker known as "blood-specific methylation-microhaplotype". This marker was designed to the detection of blood and the determination of blood donor within blood-containing mixtures. According to the selection criteria mentioned in the Materials and Methods section, we selected 10 blood-specific methylation-microhaplotype loci for inclusion in this study. Among these loci, eight exhibited blood-specific hypomethylation, while the remaining two displayed blood-specific hypermethylation. Based on data obtained from 124 individual samples in our study, the combined discrimination power (CPD) of these 10 successfully sequenced loci was 0.999999298. The sample allele methylation rate (Ram) was obtained from massive parallel sequencing (MPS), which was defined as the proportion of methylated reads to the total clustered reads that were genotyped to a specific allele. To develop an allele type classification model capable of identifying the presence of blood and the blood donor, we used the Random Forest algorithm. This model was trained and evaluated using the Ram distribution of individual samples and the Ram distribution of simulated shared alleles. Subsequently, we applied the developed allele type classification model to predict alleles within actual mixtures, trying to exclude non-blood-specific alleles, ultimately allowing us to identify the presence of blood and the blood donor in the blood-containing mixtures. Our findings demonstrate that these blood-specific methylation-microhaplotype loci have the capability to not only detect the presence of blood but also accurately associate blood with the true donor in blood-containing mixtures with the mixing ratios of 1:29, 1:19, 1:9, 1:4, 1:2, 2:1, 7:1, 8:1, 31:1 and 36:1 (blood:non-blood) by DNA mixture interpretation methods. In addition, the presence of blood and the true blood donor could be identified in a mixture containing four body fluids (blood:vaginal fluid:semen:saliva = 1:1:1:1). It is important to note that while these loci exhibit great potential, the impact of allele dropouts and alleles misidentification must be considered when interpreting the results. This is a preliminary study utilising blood-specific methylation-microhaplotype as a complementary tool to other well-established genetic markers (STR, SNP, microhaplotype, etc.) for the analysis in blood-containing mixtures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Blood-containing mixtures often appear in murder and robbery cases, and their identification plays a significant role in solving crimes. In recent years, the co-detection of DNA methylation markers (CpG) and single nucleotide polymorphism (SNP) markers has been shown to be a promising tool for the identification of semen and its donor. However, similar research on blood stains that are frequently found at crime scenes has not yet been reported. In this study, we employed blood-specific CpG-linked SNP markers (CpG-SNP) for blood-specific genotyping and the linking of blood and its donor. The tissue-specific CpG markers were screened from the literature and further verified by combining bisulfite conversion with amplification-refractory mutation system (ARMS) technology. Meanwhile, adjacent SNP markers with a minor allele frequency (MAF) greater than 0.1 were selected within 400 bp upstream and downstream of the CpG markers. SNP genotyping was performed using SNaPshot technology on a capillary electrophoresis (CE) platform. Finally, a multiplex panel, including 19 blood-specific CpG linked to 23 SNP markers, as well as 1 semen-specific CpG, 1 vaginal secretion-specific CpG, and 1 saliva-specific CpG marker, was constructed successfully. The panel showed good tissue specificity and blood stains stored at room temperature for up to nine months and moderately degraded (4 < DI < 10) could be effectively identified. Moreover, it could also be detected when blood content in the mixed stains was as low as 1%. In addition, 15 ng of DNA used for bisulfite conversion was required for obtaining a complete profile. The cumulative discrimination power of the panel among the Han population of northern China could reach 0.999983. This is the first investigation conducted for the simultaneous identification of blood and its donor regardless of other body fluids included in mixed stains. The successful construction of the panel will play a vital role in the comprehensive analysis of blood-containing mixtures in forensic practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The identification of the type of body fluid in crime scene evidence may be crucial, so that the efforts are high to reduce the complexity of these analyses and to minimize time and costs. Reliable immunochromatographic rapid tests for specific and sensitive identification of blood, saliva, urine and sperm secretions are already routinely used in forensic genetics. The recently introduced Seratec® PMB test is said to detect not only hemoglobin, but also differentiate menstrual blood from other secretions containing blood (cells) by detecting D-dimers. In our experimental set-up, menstrual blood could be reliably detected in mock forensic samples. Here, the result was independent of sample age and extraction buffer volume. It was also successfully demonstrated that all secretions without blood cells were negative for both, hemoglobin (P) and D-dimer (M). However, several blood cell-containing secretions/tissues comprising blood (injury), nasal blood, postmortem blood and wound crust also demonstrated positive results for D-dimer (M) and were therefore false positives. For blood (injury) and nasal blood, this result was reproduced for different extraction buffer volumes. The results of this study clearly demonstrate that the Seratec® PMB test is neither useful nor suitable for use in forensic genetics because of the great risk of false positive results which can lead to false conclusions, especially in sexual offense or violent acts., (© 2023. The Author(s).)

Sexual problems are common complaints across countries and cultures, and behavioral immune system theory suggests disgust plays an essential role in sexual functioning. The current study investigated 1) if disgust induced by sexual body fluids would reduce sexual arousal, reduce the likelihood of sexual engagement, and enhance disgust toward subsequent erotic stimuli, and 2) if the administration of ginger would affect these reactions. We administered either ginger or placebo pills to a sample of 247 participants ( M age  = 2.52; 122 women) and asked them to complete either behavioral approach tasks with sexual body fluids or with neutral fluids. Next, participants viewed and responded to questions concerning erotic stimuli (nude and seminude pictures of opposite-sex models). As expected, the sexual body fluids tasks induced disgust. The elevated disgust induced by sexual body fluids tasks resulted in lower sexual arousal in women, whereas ginger consumption counteracted this inhibiting effect of disgust on sexual arousal. Disgust elicited by sexual body fluids also increased disgust toward the subsequent erotic stimuli. Ginger increased sexual arousal toward the erotic stimuli in both men and women who had completed the neutral fluids tasks. Findings provide further evidence of the role of disgust in sexual problems, and, importantly, that ginger may improve the sexual function of individuals via its sexual arousal-enhancing effect.SD  = 2.52; 122 women) and asked them to complete either behavioral approach tasks with sexual body fluids or with neutral fluids. Next, participants viewed and responded to questions concerning erotic stimuli (nude and seminude pictures of opposite-sex models). As expected, the sexual body fluids tasks induced disgust. The elevated disgust induced by sexual body fluids tasks resulted in lower sexual arousal in women, whereas ginger consumption counteracted this inhibiting effect of disgust on sexual arousal. Disgust elicited by sexual body fluids also increased disgust toward the subsequent erotic stimuli. Ginger increased sexual arousal toward the erotic stimuli in both men and women who had completed the neutral fluids tasks. Findings provide further evidence of the role of disgust in sexual problems, and, importantly, that ginger may improve the sexual function of individuals via its sexual arousal-enhancing effect.

Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs. But in some cases, it can be responsible for an AAF following contamination. We report the case of an athlete who contaminated herself by exchanging body fluids while kissing her boyfriend, who took 25 mg per day of MK-2866 for 9 days prior to the athlete's AAF (urinary concentration evaluated at 13 ng/mL) without her knowledge. Both subjects came to our lab for hair testing. The athlete's hair was black and slightly frizzy. Six segments of 2 cm then 7 × 3 cm (33 cm) were analysed and showed increasing concentrations, from 2 pg/mg on the first segment to 17.8 pg/mg on the last segment. The boyfriend's hair, light-brown, analyzed on 4 × 2 cm, also showed increasing values, from 65 to 143 pg/mg. These gradients of concentration in the hair's athlete and in her boyfriend were compatible with external contamination of the hair, confirmed by analysis of washing baths, pillowcases (150 pg on each), and the athlete's hairbrush (250 pg). Fingernails were also contaminated, with 21 pg/mg in the athlete and 1041 pg/mg in the boyfriend, with highly contaminated washing baths, and toenails were less contaminated, with 2 pg/mg in the athlete and 17.3 pg/mg in the boyfriend. Urine samples taken 35 days after the start of MK-2866 treatment showed a value of 3690 ng/mL in the boyfriend and 5.7 ng/mL in the athlete. After 6 days off, these concentrations were 3.3 ng/mL and 0.1 ng/mL, respectively. A controlled transfer study was carried out 12 days after discontinuation (urine concentrations returned to negative level). After administration of 17 mg (the 25 mg/mL vial having been controlled at 17 mg/mL), urine samples were taken from the boyfriend and the athlete (n = 10 for each) for more than 25 h after they had been living normally with each other (regular kissing in particular). The boyfriend's urine concentrations ranged from 681 ng/mL to 12822 ng/mL (Tmax = 8:30 hrs), and the athlete's from 0.3 ng/mL to 13 ng/mL with Tmax = 8:30 hrs, i.e. at 22:30 hrs, which corresponded exactly to the time of collection of the urine that showed AAF, with a similar concentration. The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case., Competing Interests: Conflict of interest JCA declare conflict of interest being the expert witness of the athlete., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To observe the effect of penetrating-moxibustion therapy on postpartum uterine involution., Methods: Eighty puerpera were randomized into an observation group and a control group, 40 cases in each one. In the control group, oxytocin injection was administered by intravenous drip, 20 U each time, once daily. In the observation group, on the base of the treatment as the control group, the penetrating-moxibustion therapy was used at Shenque (GV 8), Qihai (CV 6) and Guanyuan (CV 4), 30 min to 40 min each time, twice a day. The intervention of each group started from the first day after childbirth and lasted 3 days. The uterine volume before and after treatment, and in 42 days of postpartum, the height decrease of the fundus of the uterus, the score of visual analogue scale (VAS) for uterine contraction, the volume of lochia rubra in 1 to 3 days of treatment, and lochia duration were compared between the two groups; and the clinical effect was evaluated., Results: The uterine volume in the observation group was smaller than that of the control group after treatment ( P <0.01). In 1 to 3 days of treatment, the height decrease of the fundus of the uterus in the observation group was larger ( P <0.01), VAS scores of uterine contraction were lower ( P< 0.05, P< 0.01), the lochia rubra volume was less ( P <0.01) than those in the control group. The duration of lochia rubra and lochia was shorter ( P <0.01) in the observation group when compared with that of the control group. The favorable rate of uterine involution in the observation group was 95.0% (38/40), higher than that of the control group (75.0%, 30/40, P< 0.05)., Conclusions: Penetrating-moxibustion therapy accelerates the recovery of the uterine volume, relieves uterine contraction, shortens the duration of lochia, reduces the lochia volume and promotes the postpartum uterine involution.

Maze-solving is a classical mathematical task, and is recently analogously achieved using various eccentric media and devices, such as living tissues, chemotaxis, and memristors. Plasma generated in a labyrinth of narrow channels can also play a role as a route finder to the exit. In this study, we experimentally observe the function of maze-route findings in a plasma system based on a mixed discharge scheme of direct-current (DC) volume mode and alternative-current (AC) surface dielectric-barrier discharge, and computationally generalize this function in a reinforcement-learning model. In our plasma system, we install two electrodes at the entry and the exit in a square lattice configuration of narrow channels whose cross section is 1×1 mm2 with the total length around ten centimeters. Visible emissions in low-pressure Ar gas are observed after plasma ignition, and the plasma starting from a given entry location reaches the exit as the discharge voltage increases, whose route converging level is quantified by Shannon entropy. A similar short-path route is reproduced in a reinforcement-learning model in which electric potentials through the discharge voltage is replaced by rewards with positive and negative sign or polarity. The model is not rigorous numerical representation of plasma simulation, but it shares common points with the experiments along with a rough sketch of underlying processes (charges in experiments and rewards in modelling). This finding indicates that a plasma-channel network works in an analog computing function similar to a reinforcement-learning algorithm slightly modified in this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sakai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

With nephrolithiasis projected to affect 25% of the global population in the next three decades, there is an urgent call for innovative management strategies to prevent and reduce stone recurrence. This study aims to explore the evolving management needs in nephrolithiasis from both patient and healthcare provider perspectives. An expert-collaborative online survey comprising 10 targeted questions on kidney stone management was developed and disseminated. This survey was designed to gather comprehensive insights from patients, physicians and dietician and other person in the field of nephrolithiasis. Analysis of responses from 120 participants, including 45 nephrologists, 38 dieticians, 11 urologists, and 14 kidney stones patients followed in our hospital, revealed critical insights. A significant 97.5% emphasized the necessity of optimizing daily water intake, and 94.1% recognized the need for practical dietary modifications. Additionally, 88.3% of respondents found timely hydration reminders beneficial. Notably, monitoring urine color and pH was valued by 85% and 84.3% of the participants, respectively. A striking disparity emerged in the perception of fatigue and wellness monitoring, with 65% of patients prioritizing fatigue monitoring, a view less shared by healthcare professionals. Similarly, 71% of patients deemed wellness monitoring essential, highlighting a gap in understanding between patients and their caregivers. This study underscores the critical need for more tailored guidance on hydration strategies and the promise of remote urine parameters monitoring in nephrolithiasis management. The findings strongly advocate for a patient-centered approach, aligning medical recommendations with patient lifestyles and experiences, to enhance the effectiveness of nephrolithiasis management., (© 2024. The Author(s).)

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).

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC-MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.

Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.

The development of self-powered sterilizers has garnered significant attention in the scientific and engineering fields. However, there remains an urgent need to improve their sterilization efficiency. In this study, we present a self-powered sterilizer with superior antibacterial capability by maximizing the utilization of breakdown discharge generated by a soft-contact freestanding rotary triboelectric nanogenerator (FR-TENG). To achieve this, a collaborative optimization strategy is proposed, encompassing the structural design of the FR-TENG, the implementation of double voltage rectification, and manipulation of the gaseous phase. Through a comprehensive analysis of antibacterial rates and microscopic images, the effectiveness of the self-powered sterilizer against various types of bacteria, including Gram-positive and Gram-negative species, as well as mixed bacteria in natural seawater, is demonstrated. Further investigations into bacterial morphologies and solution compositions reveal that the synergistic effect between electroporation and the generation of reactive oxygen/nitrogen species contributes to efficient sterilization. Additionally, controlled trials and molecular dynamics simulations are conducted to quantitatively elucidate the synergistic antibacterial effect between electroporation and reactive oxygen/nitrogen species. This study highlights the effectiveness of the collaborative optimization strategy in enhancing the sterilization efficiency of self-powered sterilizers while providing valuable insights into the synergistic antibacterial mechanisms of physical and chemical sterilization.

Background: Healthcare workers (HCW) are exposed to infectious agents within biological materials including blood, tissues, other body fluids and on medical supplies, contaminated surfaces within the care delivery environment. Trends in occupational injuries are influenced by the level of awareness and observance of standard precautions (SP) among HCWs. This study aimed to assess the level of awareness of SP, exposure to body fluids, reporting pattern and management among HCWs in a Referral Hospital., Methods: The present hospital-based cross-sectional study was carried out from 1st November 2020 to 31st May 2021. The exhaustive sampling method was used and a total of 120 consenting HCWs were invited to participate. A self-administered questionnaire addressed questions related to knowledge, experience, circumstances of exposure, reporting, management of occupational exposure to body fluids, hepatitis B vaccination status. Data were analyzed using R Statistic version 4.3.1. A p-value < 0.05 was considered significant., Results: Out of the 120 participating HCWs, 104 (86.7%) reported at least one accidental exposure to body fluids over the last year. Men (aOR = 4.19; p = 0.277) and HCWs aged 35 and over (aOR = 4.11; p = 0.114) were more at risk for AEB even though the difference was not statistically significant. Nurses/midwives (aOR = 65.9; p-value = 0.0005) and cleaners (aOR = 14.7; p-value = 0.0438) faced the highest risk of exposure. Lack of knowledge (79%) and patient agitation (49%) were the most reported reasons for exposure. Half of the participants (53%) reported that they used a personal protective equipment during care. Face mask (59.2%) and gowns (30.8%) were the most commonly used PPE. Most HCWs (62%) did not report AEB. Half of the affected HCWs (50.8%) received a course of post-exposure antiretroviral therapy. Few HCWs (4.2%) were fully immunized against Hepatitis B., Conclusions: Most HCWs reported an accidental exposure to body fluids over the last year. Midwives and nurses were disproportionally affected socio-professional groups. Two-thirds of the AEB were undeclared. Only half of the participants reported using PPE systematically. Hepatitis B vaccination coverage was low. There is need to strengthen the observance of standard precautions, including preventive vaccination and the systematic reporting and management of AEB., (© 2024. The Author(s).)

Identification and the time since deposition (TsD) estimation of body fluid stains from a crime scene could provide valuable information for solving the cases and are always difficult for forensics. Microbial characteristics were considered as a promising biomarker to address the issues. However, changes in the microbiota may damage the specific characteristics of body fluids. Correspondingly, incorrect body fluid identification may result in inaccurate TsD estimation. The mutual influence is not well understood and limited the codetection. In the current study, saliva, semen, vaginal secretion, and menstrual blood samples were exposed to indoor conditions and collected at eight time points (from fresh to 30 days). High-throughput sequencing based on the 16S rRNA gene was performed to characterize the microbial communities. The results showed that a longer TsD could decrease the discrimination of different body fluid stains. However, the accuracies of identification still reached a quite high value even without knowing the TsD. Correspondingly, the mean absolute error (MAE) of TsD estimation significantly increased without distinguishing the types of body fluids. The predictive TsD of menstrual blood reached a quite low MAE (1.54 ± 0.39 d). In comparison, those of saliva (6.57 ± 1.17 d), semen (6.48 ± 1.33 d), and vaginal secretion (5.35 ± 1.11 d) needed to be further improved. The great effect of individual differences on these stains limited the TsD estimation accuracy. Overall, microbial characteristics allow for codetection of body fluid identification and TsD estimation, and body fluids should be identified before estimating TsD in microbiome-based stain analyses.IMPORTANCEEmerged evidences suggest microbial characteristics could be considered a promising tool for identification and time since deposition (TsD) estimation of body fluid stains. However, the two issues should be studied together due to a potential mutual influence. The current study provides the first evidence to understand the mutual influence and determines an optimal process for codetection of identification and TsD estimation for unknown stains for forensics. In addition, we involved aged stains into our study for identification of body fluid stains, rather than only using fresh stains like previous studies. This increased the predictive accuracy. We have preliminary verified that individual differences in microbiotas limited the predictive accuracy of TsD estimation for saliva, semen, and vaginal secretion. Microbial characteristics could provide an accurate TsD estimation for menstrual blood. Our study benefits the comprehensive understanding of microbiome-based stain analyses as an essential addition to previous studies., Competing Interests: The authors declare no conflict of interest.

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease., (© 2024. The Author(s).)

In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor β (TGF-β), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFβ, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure., (© 2024 John Wiley & Sons Australia, Ltd.)

Early chronic kidney disease (CKD) has strong concealment and lacks an efficient, non-invasive, and lable-free detection platform. Cystatin C (Cys C) in urine is closely related to the progress of CKD (especially at the early stage), which is an ideal endogenous marker to evaluate the impairment of renal function. Thus, the accurate detection of urinary Cys C (u-Cys C) is great significant for early prevention and treatment and delaying the course of the disease of CKD patients. Herein, we developed an extended-gate field-effect transistor (EG-FET) sensor for ultrasensitive detection of u-Cys C, which consists of a monolithic interface-engineered graphene EG electrode array and a commercially available MOSFET. Laser-induced graphene (LIG) loaded with sputtered Au NPs in the presence of adhesive Cr (Au NPs/Cr/LIG) boosts the electrical performance of the EG electrode. Meanwhile, Au NPs also serve as linkers to immobilize papain that can selectively form protein complexes with Cys C. Supported by the synergistic effect of multilevel interface-engineered graphene, our sensor exhibits a good linear correlation within the u-Cys C concentration range of 5 ag/μL to 50 ng/μL with low detection limit of 0.05 ag/μL. Our work makes accurate, specific and rapid detection of u-Cys C feasible and promising for early screening for CKD., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This graduate student literature review provides an examination of the ontological adaptations of the calf's immune system and how the intestinal microbiota influences calf immune function in health and disease. Within dairy rearing systems, various nutritional and management factors have emerged as critical determinants of development influencing multiple physiological axes in the calf. Furthermore, we discuss how multiple pre- and postnatal maternal factors influence the trajectory of immune development in favor of establishing regulatory networks to successfully cope with the new environment, while providing early immune protection via immune passive transfer from colostrum. Additionally, our review provides insights into the current understanding of how the intestinal microbiota contributes to the development of the intestinal and systemic immune system in calves. Lastly, we address potential concerns related to the use of prophylactic antimicrobials and waste milk, specifically examining their adverse effects on intestinal health and metabolic function. By examining these factors, we aim to better understand the intricate relationship between current management practices and their long-term effect on animal health., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere with viral attachment and entry. Consequently, physiological concentrations of EVs applied in vitro efficiently inhibited infection by apoptotic mimicry dengue, West Nile, Chikungunya, Ebola and vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus 1, hepatitis C virus and herpesviruses that use other entry receptors. Our results identify the role of PS-rich EVs in body fluids in innate defence against infection via viral apoptotic mimicries, explaining why these viruses are primarily transmitted via PS-EV-deficient blood or blood-ingesting arthropods rather than direct human-to-human contact., (© 2024. The Author(s).)

Supercapacitors, pivotal in mitigating the energy crisis stemming from dwindling fossil fuel reservoirs, necessitate meticulous consideration of electrode material preparation. While lignin-derived carbon materials sourced sustainably exhibit commendable potential as electrode materials, their intrinsic low capacitance limits widespread utilization. Herein, nitrogen atom doping of lignin (CNL) was accomplished employing a chemical modification technique employing cyanuric chloride as a dopant. The resultant nitrogen content measured at 2.85 %. Subsequent to CNL carbonation, the generated C 3 N 4 was selectively confined to the internal surface of the CNLMS-800 through a domain-limited activation method, thereby rendering it suitable for deployment as a supercapacitor electrode material. CNLMS-800 manifests a substantial specific surface area of 1778.0 m 2  g -1 and a concomitantly diminutive pore size of 2.6 nm. Noteworthy, the specific capacitance of CNLMS-800 attains 473.0 F g -1 at a current density of 0.5 A g -1 in a 6 M KOH electrolyte. The resultant energy density reaches 39.0 Wh kg -1 at a power density of 338.0 W kg -1 . Crucially, even after 20,000 charge/discharge cycles at a current density of 10 A g -1 , the capacitance retention attains an impressive 87.5 % in the KOH electrolyte. This innovative utilization of sustainable resources for electrode fabrication epitomizes a seminal advancement in the field of energy technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Transcatheter edge-to-edge repair (TEER) is typically used to treat mitral regurgitation (MR) in patients with high surgical risk. Increased post-procedural mitral valve gradient (MVG) may impact mortality and hospitalizations. We aim to evaluate and compare the absolute postprocedural MVG and the change in the MVG effect on outcomes for patients undergoing TEER therapy., Methods: Patients who underwent TEER for severe MR were divided into two groups, initially by postprocedural absolute MVG, TTE-based at discharge, and then by the difference between preprocedural and postprocedural MVG. Primary endpoints included all-cause mortality and heart failure hospitalization (HFH) during one year after the procedure., Results: The study included 100 patients. The mean MVG increased from 3.39 mmHg immediately after the procedure to 4.83 mmHg the following day, an increase of 1.44 mmHg (p < 0.001). First stratification was by MVG on the day following the procedure - MVG ≤5 mmHg (n = 70) and MVG >5 mmHg (n = 30). There was no significant difference in rates of survival (88.6%, 93.3%, p = 0.716) or HFH (18.6%, 33.3%, p = 0.178). Second stratification was by the difference in preprocedural and postprocedural MVG- delta MVG <3 mmHg (n = 55) and delta MVG ≥3 mmHg (n = 45). While survival rates did not significantly differ (87.3% vs. 93.3%, p = 0.503), delta MVG ≥3 mmHg correlated with higher HFH rates (12.7% vs. 35.6%, p = 0.014)., Conclusions: The MVG of patients undergoing TEER usually increases on the day after the procedure compared to the immediate post-procedure MVG. Higher delta MVG is associated with higher HFH rate., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: The aim of the study was to store urine samples at different temperatures and humidity levels and analyze common biochemical test results and point-of-care testing (POCT) indicators according to different storage times and evaluate whether the samples should be centrifuged to study the best storage conditions for urine samples. Methods: Random midstream urine samples (100 mL) were collected from 10 healthy individuals. A portion of the samples was centrifuged. The remaining samples were not centrifuged and were stored under different temperature and humidity conditions for different periods. We measured urine indicators ([Na+], [K+], [Cl-], gamma-glutamyl transpeptidase [GGT], urea, and creatinine [Cr]) at 2, 4, 24, and 72 hours and 7 and 55 days, and we used POCT to measure myoglobin (Mb) and microalbumin (mAlb) concentrations. Results: Centrifugation of urine samples decreased the measured GGT and increased the measured Mb. In urine samples stored at 4°C and room temperature, electrolyte concentrations were scarcely affected by storage time. After storage at 50°C for 24 hours, the measured [Na + ] and [Cl - ] levels changed. Metabolites (urea and Cr) underwent no obvious change across temperatures. GGT did not change during long-term storage at 4°C. The mAlb level changed significantly only after storage at 4°C. When stored at 4°C, Mb changed little within 4 hours. Under humid conditions, [Na + ] and [Cl - ] increased significantly after 24 hours, and urea decreased significantly after 7 days of storage. Under dry storage conditions, urinary Cr and GGT decreased, and under humid conditions, these concentrations increased. At high humidity, mAlb increased significantly after 72 hours. Conclusions: Electrolyte and amino acid metabolite concentrations were less affected by storage time at 4°C and room temperature than at other temperatures. Some proteins are sensitive to environmental changes; samples collected for quantification of these proteins can be stored briefly at 4°C after centrifugation. Normal humidity conditions meet most physiological testing requirements.

Background: Traumatic subdural effusion (TSDE) may increase progressively or evolve into chronic subdural hematoma. These events, defined as deterioration of the effusion, often require close observation or even surgical treatment. The aim of our study was to develop and validate a nomogram for predicting the possibility of an effusion deteriorating in patients with TSDE based on the available clinical characteristics., Methods: Clinical data from 78 patients with TSDE were retrospectively analyzed. All patients were admitted from January 2019 to May 2022. Logistic regression was applied to the data to screen for independent predictors of effusion deterioration within six months; then, a predictive nomogram model was established in R language. The consistency, predictive accuracy and clinical utility of the model were evaluated with the C-index, calibration plots, ROC curves and decision curve analysis (DCA). Furthermore, we performed internal validation using a bootstrap approach to assess the effectiveness of the model., Results: Time of effusion after trauma, maximum thickness of the effusion, CT value of the effusion as well as the use of atorvastatin were identified as predictors in the nomogram. The predictive model was well calibrated and demonstrated good discrimination (C-index: 0.893). The AUC of the model was 0.893 (95% CI: 0.824-0.962), and the modified C-index (0.865) indicated excellent performance in the internal validation. In addition, DCA revealed that the nomogram had clinical value., Conclusions: This predictive model can effectively assess the risk of effusion deterioration in TSDE patients within six months and identify high-risk patients early., Competing Interests: Declaration of Competing Interest We have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity., (© 2023 John Wiley & Sons Ltd.)

Human milk contains extracellular vesicles (HMEVs). Pre-clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density-gradient ultracentrifugation following two-step skimming, acid precipitation of caseins, and multi-step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super-resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of β-casein and lactalbumin. HMEV and some dEV fractions contain mammary gland-derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin-mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

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.

The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection., Competing Interests: The authors declare no conflicts of interest.

Serous cavity effusion is a prevalent pathological condition encountered in clinical settings. Fluid samples obtained from these effusions are vital for diagnostic and therapeutic purposes. Traditionally, cytological examination of smears is a common method for diagnosing serous cavity effusion, renowned for its convenience. However, this technique presents limitations that can compromise its efficiency and diagnostic accuracy. This study aims to overcome these challenges and introduce an improved method for the precise detection of malignant cells in serous cavity effusions. We have developed a transformer-based classification framework, specifically employing the vision transformer (ViT) model, to fulfill this objective. Our research involved collecting smear images and corresponding cytological reports from 161 patients who underwent serous cavity drainage. We meticulously annotated 4836 patches from these images, identifying regions with and without malignant cells, thus creating a unique dataset for smear image classification. The findings of our study reveal that deep learning models, particularly the ViT model, exhibit remarkable accuracy in classifying patches as malignant or non-malignant. The ViT model achieved an impressive area under the receiver operating characteristic curve (AUROC) of 0.99, surpassing the performance of the convolutional neural network (CNN) model, which recorded an AUROC of 0.86. Additionally, we validated our models using an external cohort of 127 patients. The ViT model sustained its high-level screening performance, achieving an AUROC of 0.98 at the patient level, compared to the CNN model's AUROC of 0.84. The visualization of our ViT models confirmed their capability to precisely identify regions containing malignant cells in multiple serous cavity effusion smear images. In summary, our study demonstrates the potential of deep learning models, particularly the ViT model, in automating the screening process for serous cavity effusions. These models offer significant assistance to cytologists in enhancing diagnostic accuracy and efficiency. The ViT model stands out for its advanced self-attention mechanism, making it exceptionally suitable for tasks that necessitate detailed analysis of small, sparsely distributed targets like cellular clusters in serous cavity effusions., (© 2024. The Author(s).)