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Selective and sensitive sarcosine detection is crucial due to its recent endorsement as a prostate cancer (PCa) biomarker in clinical diagnosis. The reduced graphene oxide-cobalt nickel tungsten boron oxides (CoNiWBO/rGO) nanocomposite is developed as a non-enzymatic electrochemical sensor for sarcosine detection in PCa patients' serum. CoNiWBO/rGO is synthesized by the chemical reduction method via a one-pot reduction method followed by calcination at 500 °C under a nitrogen environment for 2 h and characterized by UV-Vis, XRD, TGA, and SEM. CoNiWBO/rGO is then deposited on a glassy carbon electrode, and sarcosine sensing parameters are optimized, including concentration and pH. This non-enzymatic sensor is employed to directly determine sarcosine in serum samples. Differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) are employed to monitor the electrochemical behavior where sarcosine binding leads to oxidation. Chronoamperometric studies show the stability of the developed sensor. The results demonstrate a wide linear range from 0.1 to 50 µM and low limits of detection, i.e., 0.04 µM and 0.07 µM using DPV and LSV respectivel. Moreover, the calculated recovery of sarcosine in human serum of prostate cancer patients is 78–96%. The developed electrochemical sensor for sarcosine detection can have potential applications in clinical diagnosis. [ABSTRACT FROM AUTHOR]

The main hurdles with current therapies for major depressive disorder (MDD) include lack of efficacy, therapeutic latency, and adverse drug reactions. Add-on therapy to conventional antidepressants may result in better therapeutic outcomes to overcome these obstacles. Sarcosine (N-methyl glycine), an endogenous amino acid that acts by modulating the NMDA receptor, is available as a dietary supplement. So, the present study was planned to evaluate the efficacy and safety of add-on sarcosine to SSRIs in MDD. In the present randomized, double-blind clinical trial (NCT04975100), 60 eligible participants with MDD were randomly assigned to either the test group (SSRI + sarcosine) or the control group (SSRI + placebo). Clinical and biochemical parameters like MADRS, CGI, serum BDNF, and serum glycine were assessed at baseline and eight weeks. The mean reduction in MADRS score was significant in both the control (−8.7, 95% CI: −11.0 to −6.4, p < 0.001) and the test group (−13.3, 95% CI: −14.9 to −11.7, p < 0.001), but the change in the test group was significantly greater (−4.6, 95% CI: −7.5 to −1.7, p = 0.003). The test group had a significantly higher response rate (p = 0.007) and remission rate (p = 0.038) compared to the control group. There was a significant increase in serum BDNF in both groups; however, the change in the test group was significantly higher than in the control group (p = 0.041). Similarly, the test group had a significantly higher increase in serum glycine than the control group (p < 0.001). Sarcosine may be considered an efficacious and safe add-on therapy to standard SSRIs in the management of MDD. ClinicalTrial.gov IdentifierNCT04975100. [ABSTRACT FROM AUTHOR]

Recycled cellulose extracted from office wastepaper is an attractive material for manufacturing disposable sensors. By formulating a cellulose hydrogel nanocomposite, the sensitivity of the colorimetric sensor is notably improved, enabling simple observation of the color changes with the naked eye. In this study, a recycled cellulose/PVA/CMC-GO/NQS hydrogel nanocomposite was successfully prepared and applied as a noninvasive wearable sarcosine sensor integrated into a diaper. The prepared hydrogel-based colorimetric sensor operates via a nonenzymatic reaction using 1,2-naphthoquinone-4-sulfonic acid sodium salt (NQS) as a coloring reagent. NQS-functionalized graphene oxide (GO) facilitates the color-producing reaction by increasing NQS molecules adhering to both sides of the GO sheet via π-π interactions. This sensor exhibits a dramatic color change with a linear range of 0–100 μM (R2 = 0.9550) and a detection limit of 10.0 μM, indicating that sarcosine can be effectively detected at its cutoff value (25.0 μM) for detecting prostate cancer (PCa). The sensing results tested in human urine samples were validated with a standard LDI-MS, which provided satisfactory results. Consequently, this sensor might be an alternative wearable sarcosine sensor for prostate cancer screening in the near future. [ABSTRACT FROM AUTHOR]

An original molecular imprinting photoelectrochemical (PEC) sensor for sarcosine detection based on stable lead-free inorganic halide double perovskite Cs2AgBiBr6 is proposed. Cs2AgBiBr6 as a lead-free halide perovskite material possesses several positive optoelectronic properties for PEC analysis, such as long-lived component to the charge-carrier lifetime, and strong absorption of visible light. At the same time, two-dimensional materials also offer excellent electronic and mechanical properties; thus, Bi2O2S was used and combined with Cs2AgBiBr6 to provide a stable and large photocurrent, which also benefits from the stability of perovskite Cs2AgBiBr6. Based on this novel PEC assay, the detection range for sarcosine was between 0.005 and 5000 ng/mL with a low detection limit of 0.002 ng/mL. This work also improved the adhibition of metal halide perovskite in analytical chemistry field, providing a novel way for other small molecule detection. [ABSTRACT FROM AUTHOR]

Introduction: A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed. Methods: We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC). Results: Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores. Conclusion: Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female. [ABSTRACT FROM AUTHOR]

Sarcosine is an important marker for the diagnosis of prostate cancer in urine. A chemiluminescence (CL) sensor based upon silver doped iron-based metal-organic gels (Ag/Fe-MOGs) was constructed for sarcosine determination. The Ag/Fe-MOGs with peroxidase-like activities were synthesized by a simple room temperature method to catalyze hydrogen peroxide to generate reactive oxygen species. During detection, sarcosine was oxidized by sarcosine oxidase (SOx) to produce H2O2 which was catalyzed by Ag/Fe-MOGs and accompanied by luminol chemiluminescence. Due to the peroxidase-like activity and high stability of Ag/Fe-MOGs, the luminol chemiluminescence was applied to measure sarcosine from 1 to 50 mM with a detection limit of 0.23 mM. Practical applicability was validated by determining sarcosine in human urine. This work not only offers a simple approach to a prepare catalyst with enzyme-like activity, but also provides an efficient and sensitive strategy for other substances in a rapid and cost-effective approach by replacing enzymes. [ABSTRACT FROM AUTHOR]

Aim: To quantify the association between serum sarcosine and diabetic retinopathy (DR) using weighted gene co‐expression network analysis (WGCNA). Methods: We measured serum metabolites in 69 pairs of type 2 diabetes (T2D) patients with and without DR matched by age, gender, body mass index（BMI and HbA1c, using a propensity score matching‐based approach. To identify modules and metabolites linked to DR, pathway analysis was performed using WGCNA, the Kyoto Encyclopedia of Genes and Genomes and Small‐Molecule Pathway Database. The association of sarcosine with DR was estimated by restricted cubic spline and conditional logistic regression models. Its joint effects with covariates on DR were also extensively examined. Results: With per interquartile range elevation of sarcosine, the adjusted odds ratio (AOR) of DR significantly decreased by 67% (AOR: 0.33, 95% confidence interval [CI]: 0.19‐0.58). Similar results were also found in the tertile analysis. Compared with those in the first tertile of sarcosine, the AOR significantly decreased by 54% (AOR: 0.46, 95% CI: 0.18‐1.17) and 78% (AOR: 0.22, 95% CI: 0.08‐0.59) for subjects in the second and third tertiles, respectively. Compared with subjects with lower sarcosine and lower HDL‐C levels, those with higher sarcosine and lower HDL‐C levels had the lowest odds of DR (OR: 0.13, 95% CI: 0.04, 0.43). Conclusions: Serum sarcosine was inversely related to DR, especially in T2D patients with insufficient HDL‐C. This study provides insights on a possible novel target for DR precision prevention and control, as well as a better understanding of the DR mechanism. [ABSTRACT FROM AUTHOR]

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated. [ABSTRACT FROM AUTHOR]

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine (n = 28) or placebo (n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels. [ABSTRACT FROM AUTHOR]

IntroductionA group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.MethodsWe identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).ResultsThrough these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.ConclusionOur study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Multicomponent heteronanostructures offering catalytic and optical properties have applications across various fields. Photonic crystals (diatom frustules) coated with Au and copper chalcogenide domains represent a unique nanosystem that integrates multiple plasmon resonances from guided-mode resonance, conduction electrons, and valence holes in a single nanoscale system. In this work, we fabricate an enzyme-assisted photonic crystal-enhanced plasmonic nanosystem using a live diatom (Thalassiosira pseudonana) for surface-enhanced Raman scattering (SERS) quantification of sarcosine, an early stage prostate cancer (PCa) biomarker. The biosynthesized heteronanostructure was constructed by coating bimetallic nanoparticles (Au/CuX) on the diatom frustule via a two-stage cultivation process. A silaffin peptide-tagged sarcosine oxidase (SoX) was designed for specific substrate recognition and oriented conjunction. The components were coupled into a single entity (SoX-immobilized Au/CuX-coated frustule, BioNPS) to overcome the interenzyme distance and analyte trade-offs between mass transport. The sarcosine detection by BioNPS outperforms suspended bimetallic nanoparticles and single NP-coated diatom frustules. The improvement is attributed to the coupling of photonic frustule guided-mode resonance to the localized surface plasmonic resonance of bimetallic NPs via both electromagnetic and CT mechanisms. The cascade reaction in close proximity greatly enhances the catalytic efficiency by 5.47-fold compared to the solution-phase assay. The biochem nanosystem precisely detects tiny sarcosine concentration changes in the urine samples of PCa patients and healthy individuals. As a proof of concept, the in vivo fabrication of photonic/plasmonic heterostructures with tunable properties holds great promise for noninvasive biomarker screening. [ABSTRACT FROM AUTHOR]

Corynebacterium glutamicum AJ1511 and Escherichia coli BW25113 strains were compared in terms of resistance to sarcosine (N-methylglycine). The E. coli strain was more sensitive to sarcosine than C. glutamicum, especially when grown in minimal medium. Growth inhibition of the BW25113 strain in minimal M9 medium containing 0.5 m sarcosine was overcome by the addition of glycine. Inactivation of the glycine cleavage (GCV) system (gcvP) as well as the removal of its activator (gcvA) in BW25113 cells increased the threshold for sarcosine inhibition up to 0.75 m. Activation of the promoter of the E. coli gcvTHP operon by 0.1-0.4 m sarcosine added to M9 medium was demonstrated in vivo using dasherGFP as the reporter. Sensitivity to sarcosine on glucose minimal medium is suggested to be a characteristic of Gram-negative bacteria with GcvA/GcvR regulation of the GCV system. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret's diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

This paper presents a novel, rapid, and simple method for the determination of sarcosine. The surface of a glass plate was modified with 3-(methacryloxy) propyltrimethoxysilane. Then, a sarcosine-imprinted polymer was grafted on the glass plate by copolymerization of the vinyl end groups with a functional monomer and a cross-linking agent. The synthesized polymers were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. In the subsequent step, the determination of sarcosine was conducted using the synthesized kit in optimized conditions. The synthesized grafted plate was able to absorb sarcosine selectively in the presence of other amino acids, showing that the proposed method enabled the rapid determination of sarcosine. [ABSTRACT FROM AUTHOR]

Ketamine offers a fast-acting approach to relieving treatment-resistant depression, but its abuse potential is an issue of concern. As ketamine is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) ion channel blocker, modulation of NMDAR might be an effective strategy to counteract the abuse liability of ketamine and even to treat ketamine use disorder. This study evaluated whether NMDAR modulators that act on glycine binding sites can decrease motivation to obtain ketamine and reduce reinstatement to ketamine-seeking behavior. Two NMDAR modulators, D-serine and sarcosine were examined. Male Sprague–Dawley rats underwent training to acquire the ability to self-administer ketamine. The motivation to self-administer ketamine or sucrose pellets was examined under a progressive ratio (PR) schedule. The reinstatement of ketamine-seeking and sucrose pellet-seeking behaviors were assessed after extinction. The results showed that both D-serine and sarcosine significantly decreased the breakpoints for ketamine and prevented reinstatement of ketamine seeking. However, these modulators did not alter motivated behavior for sucrose pellets, the ability of the cue and sucrose pellets to reinstate sucrose-seeking behavior or spontaneous locomotor activity. These findings indicate that two NMDAR modulators can specifically reduce the measures of motivation and relapse for ketamine in rats, suggesting that targeting the glycine binding site of the NMDAR is a promising approach for preventing and treating ketamine use disorder. [ABSTRACT FROM AUTHOR]

Flower-like core-shell nanostructures based on natural asphalt (NA) coated with nickel-layered double hydroxide nanosheets (Ni-LDH NSs) were synthesized for the first time. The synthetic nanostructures were successfully used as an efficient platform in the design of sarcosine (SAR) electrochemical aptasensor. SAR is considered an efficient biomarker for prostate cancer (PCa) diagnosis. However, the low concentration of SAR in urine, plasma, and tissue cells has limited the growth of SAR biosensors. The performance of the presented SAR aptasensor is very promising in being applied as a portable device in the identification of PCa. After drawing the calibration curve, the linear concentration range was obtained in two ranges from 5 pM to 100 nM and 100 nM to 7.9 μM, and the limit of detection (LOD) was calculated to be 1.6 pM. This study can provide a basis for wider research in various programs such as developing PCa diagnostic aptasensors and investigating the use of NA nanostructures in other electrochemical applications such as electrocatalysis and energy storage. [ABSTRACT FROM AUTHOR]

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection. Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models. Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively. Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens. [ABSTRACT FROM AUTHOR]

A fluorescence and colorimetric tandem dual-mode sensor was established by modulating fluorescence and oxidase-like activity via valence switching of cerium-based coordination polymer nanoparticles (Ce-CPNs) for the detection of sarcosine (Sar) which is considered as a potential biomarker for the diagnosis of prostate cancer (PCa). In the present research, sarcosine oxidase (SOX) specifically catalyzes the oxidation of Sar to yield H2O2 which can rapidly oxidize Ce(III)-CPNs to generate Ce(IV)-CPNs in appropriate alkaline solution. The generated Ce(IV)-CPNs create a markedly weakened fluorescent signal at 350 nm, while they can induce oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to generate blue TMBox through emerging good oxidase-like activity. The sensing platform can realize accurate, stable, and high-throughput detection of Sar because of the tandem dual signal output mechanism. More attractively, the chromogenic hydrogel sensing device using smartphone photographing has achieved perfect results for the on-site sensing of Sar in urine specimens without large experimental equipments, demonstrating its considerable clinical application potential in the early diagnosis of PCa. [ABSTRACT FROM AUTHOR]

Conventional luminol chemiluminescence (CL) is widely used in imaging and analytical assays. As far as we can search, there are no studies on the use of CL for information encryption and protection. Here, a novel CL hydrogel is developed. A rapid color visualization of sarcosine in urine using a mobile phone camera is achieved based on CL energy resonance transfer. Four different colors of CL hydrogels are prepared by adding different ratios of rhodamine B or fluorescein. In the multicolor CL hydrogels, activated CL can generate conventional multicolor code shift and original white light. The luminescence duration and the cause of the white light are analyzed using CL spectroscopy. Sarcosine oxidase is replaced with sarcosine in the multicolor CL hydrogels to obtain the translation of editable code, which facilitates the secondary information encryption and code transmissions. The effective luminescence time of these hydrogels are short (13–50 min), and code can be deleted naturally. [ABSTRACT FROM AUTHOR]

Screen-printing technology is a game changer in many fields including electrochemical biosensing. Two-dimensional nanomaterial MXene Ti3C2Tx was integrated as a nanoplatform to immobilise enzyme sarcosine oxidase (SOx) onto the interface of screen-printed carbon electrodes (SPCEs). A miniaturised, portable, and cost-effective nanobiosensor was constructed using chitosan as a biocompatible glue for the ultrasensitive detection of prostate cancer biomarker sarcosine. The fabricated device was characterised with energy-dispersive X-ray spectroscopy (EDX), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Sarcosine was detected indirectly via the amperometric detection of H2O2 formed during enzymatic reaction. The nanobiosensor could detect sarcosine down to 7.0 nM with a maximal peak current output at 4.10 ± 0.35 × 10−5 A using only 100 µL of a sample per measurement. The assay run in 100 μL of an electrolyte showed the first linear calibration curve in a concentration window of up to 5 μM with a slope of 2.86 μA·μM−1, and the second linear calibration curve in the range of 5–50 μM with a slope of 0.32 ± 0.01 μA·μM−1 (R2 = 0.992). The device provided a high recovery index of 92.5% when measuring an analyte spiked into artificial urine, and could be used for detection of sarcosine in urine for at least a period of 5 weeks after the preparation. [ABSTRACT FROM AUTHOR]

A new fluorescent probe based on Eu (III) incorporated BSA‐AuNCs is developed for the selective sensing of sarcosine. Sarcosine is a simple non‐proteinogenic amino acid which is a clinical biomarker for prostate cancer. The non‐invasive sensing of a metabolite biomarker sarcosine for prostate cancer from urine sample was achieved through the developed Eu (III) incorporated BSA‐AuNCs probe. The developed sensor exhibited a good sensitivity and selectivity towards the metabolite sarcosine and observed no significant interference with other coexisting metabolites present in urine. The probe shows a very lower Limit of detection (LOD) of 0.177 mM and this probe can be developed for determining sarcosine on clinical basis. Considering its predominance and the pain associated invasive prostate cancer clinical examinations for the diagnosis, a non‐invasive diagnosis is of great need and significance. [ABSTRACT FROM AUTHOR]

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated.

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine (n = 28) or placebo (n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

BackgroundThe cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.MethodsSixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.ResultsData suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.ConclusionThis pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

Solute carriers (SLC) are important membrane transport proteins in normal and pathophysiological cells. The aim was to identify amino acid SLC(s) responsible for uptake of sarcosine and glycine in prostate cancer cells and investigate the impact hereon of hyperosmotic stress. Uptake of 14C-sarcosine and 3H-glycine was measured in human prostate cancer (PC-3) cells cultured under isosmotic (300 mOsm/kg) and hyperosmotic (500 mOsm/kg) conditions for 24 h. Hyperosmotic culture medium was obtained by supplementing the medium with 200 mM of the trisaccharide raffinose. Amino acid SLC expression was studied using RT-PCR, real-time PCR, and western blotting. siRNA knockdown of SNAT2 was performed. Experiments were conducted in at least 3 independent cell passages. The uptake of Sar and Gly was increased approximately 8–ninefold in PC-3 cells after 24 h hyperosmotic culture. PAT1 mRNA and protein could not be detected, while SNAT2 was upregulated at the mRNA and protein level. Transfection with SNAT2-specific siRNA reduced Vmax of Sar uptake from 2653 ± 38 to 513 ± 38 nmol mg protein−1 min−1, without altering the Km value (3.19 ± 0.13 vs. 3.42 ± 0.71 mM), indicating that SNAT2 is responsible for at least 80% of Sar uptake in hyperosmotic cultured PC-3 cells. SNAT2 is upregulated in hyperosmotic stressed prostate cancer cells and SNAT2 is responsible for cellular sarcosine and glycine uptake in hyperosmotic cultured PC-3 cells. Sar is identified as a substrate for SNAT2, and this has physiological implications for understanding cellular solute transport in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Sphingomonas paucimobilis' P450SPα (CYP152B1) is a good candidate as industrial biocatalyst. This enzyme is able to use hydrogen peroxide as unique cofactor to catalyze the fatty acids conversion to α‐hydroxy fatty acids, thus avoiding the use of expensive electron‐donor(s) and redox partner(s). Nevertheless, the toxicity of exogenous H2O2 toward proteins and cells often results in the failure of the reaction scale‐up when it is directly added as co‐substrate. In order to bypass this problem, we designed a H2O2 self‐producing enzyme by fusing the P450SPα to the monomeric sarcosine oxidase (MSOX), as H2O2 donor system, in a unique polypeptide chain, obtaining the P450SPα‐polyG‐MSOX fusion protein. The purified P450SPα‐polyG‐MSOX protein displayed high purity (A417/A280 = 0.6) and H2O2‐tolerance (kdecay = 0.0021 ± 0.000055 min−1; ΔA417 = 0.018 ± 0.001) as well as good thermal stability (Tm: 59.3 ± 0.3°C and 63.2 ± 0.02°C for P450SPα and MSOX domains, respectively). The data show how the catalytic interplay between the two domains can be finely regulated by using 500 mM sarcosine as sacrificial substrate to generate H2O2. Indeed, the fusion protein resulted in a high conversion yield toward fat waste biomass‐representative fatty acids, that is, lauric acid (TON = 6,800 compared to the isolated P450SPα TON = 2,307); myristic acid (TON = 6,750); and palmitic acid (TON = 1,962). [ABSTRACT FROM AUTHOR]

The in vitro diagnostics of cancer are not represented well yet, but the need for early-stage detection is undeniable. In recent decades, surface-enhanced Raman spectroscopy (SERS) has emerged as an efficient, adaptable, and unique technique for the detection of cancer molecules in their early stages. Herein, we demonstrate an opto-plasmonic hybrid structure for sensitive detection of the prostate cancer biomarker sarcosine using silica nanospheres coated silver nano-islands as a facile and efficient SERS active substrate. The SERS active platform has been developed via thin (5–15 nm) deposition of silver islands using a simple and cost-effective Radio Frequency (RF) sputtering technique followed by the synthesis and decoration of silica nanospheres (~500 nm) synthesized via Stober's method. It is anticipated that the coupling of Whispering Gallery Modes and photonic nano-jets in SiO2 nanospheres induce Localized Surface Plasmon Resonance (LSPR) in Ag nano-islands, which is responsible for the SERS enhancement. The as-fabricated SERS active platform shows a linear response in the physiological range (10 nM to 100 μM) and an extremely low limit of detection (LOD) of 1.76 nM with a correlation coefficient of 0.98 and enhancement factor ~2 × 107. The findings suggest that our fabricated SERS platform could be potentially used for the rapid detection of bio-chemical traces with high sensitivity. [ABSTRACT FROM AUTHOR]

Schematic diagram depicting the synthesis process of the intelligent paper-based biosensor and its colorimetric detection application for biomarkers in urine. (FP: filter paper; CPBA: Carboxyphenylboric acid; HRP: horseradish peroxidase; TMB: 3,3′,5,5′-tetramethylbenzidine; GLU: glusose; UA: uric acid; SAR: sarcosine; GOx: glucose oxidase; UOx: urate oxidase; SOx: urate oxidase.) [Display omitted] • A green, low-cost, portable and visual intelligent paper-based biosensor was created. • This sensor immobilized HRP in horseradish by a borate-modified filter paper. • This sensor can detect many substances simultaneously and improve detection efficiency. • This sensor boasts the advantages of superior sensitivity, stability and selectivity. In the increasing demand for real-time testing, the imperative for a straightforward, rapid, portable, and effective biosensor is evident. In this study, an intelligent paper-based biosensor was developed, employing cost-effective and readily available filter paper as a matrix to prepare boronate affinity paper-based materials. The immobilization of horseradish peroxidase (HRP) from crude horseradish extract onto the material surface was realized. Ultimately, a cold assembly technique was employed to construct this intelligent paper-based biosensor, which combined with a smartphone APP, facilitated the easy, accurate, and simultaneous detection of the content of glucose (GLU), uric acid (UA), and sarcosine (SAR) in urine, significantly enhancing the convenience and practicality of real-time monitoring. Additionally, UV spectroscopy served as an auxiliary method to affirm the reliability of the detection outcomes. For the detection of GLU, UA, and SAR, the biosensor exhibited linear ranges of 2–200, 2–500, and 2–500 µmol L–1, respectively, with detection limits (LODs) of 1 µmol L–1 for all analytes. In practical urine sample analysis, the recovery rates of GLU, UA, and SAR detected by the intelligent paper-based biosensors were within a reasonable range, with relative standard deviations below 3.5 %. This fully demonstrates the high accuracy and reliability of the intelligent paper-based biosensor. The development of this low-cost, portable biosensor provides a new method for the detection of biomarkers related to H 2 O 2. [ABSTRACT FROM AUTHOR]

A portable paper-based enzyme-linked biosensor that integrates a multi-enzyme cascade reaction, natural enzyme, and nanozyme with filter paper, combined with smartphones, is proposed for the detection of xanthine (XA) and sarcosine (SA) in urine. The primary biological component of the sensor is horseradish peroxidase (HRP). By chemically modifying cellulose filter paper (CFP) the HRP in horseradish crude extract is specifically immobilized through boron affinity and metal chelation techniques. Furthermore, the incorporation of UiO-66 on CFP had a good synergistic effect on the electron transfer of HRP and the detection of H 2 O 2 , significantly increasing the sensor's sensitivity. Under optimized experimental conditions, the sensor demonstrated a dynamic response range of 8–400 μmol L−1 for SA with a minimum detection limit (LOD) of 5 μmol L−1, and a dynamic response range of 10–400 μmol L−1 with an LOD of 8 μmol L−1 for XA. Additionally, the well-designed detection area of the portable test strip simplifies the detection operation, reduces the detection time, and enables rapid on-site analysis. UV-Vis analysis further confirmed the sensor's accuracy in detecting disease markers in urine. The sensing platform has good reproducibility, specificity and stability, suitable for the detection of SA and XA in real human urine samples, and the sensor has the advantages of simple manufacturing, easy operation, strong portability, low reagent consumption, and low cost benefit. Therefore, the development of this paper-based enzyme-linked biosensor offers a novel approach to the detection of disease markers in urine and has potential applications in medical testing. [Display omitted] • Paper-based enzyme-linked biosensor was successfully prepared. • Smartphone-assisted test paper detected xanthine and sarcosine in urine. • The sensor immobilizes HRP from horseradish by modifying the filter paper. • The addition of UiO-66 had good synergistic effect on the HRP's electron transfer. • The portable test paper can realize the simultaneous detection of multiple copies. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret’s diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy.

Objective: The most common oncologic disease in men is prostate cancer. There have been studies for alternative methods for early screening. Over the past years, the interest in sarcosine as a potential marker for prostate cancer has increased. We evaluated the predictability of prostate biopsy necessity by using urine sarcosine for prostate cancer examination during our study. Methods: The study included 84 male patients aged between 45 and 79 in our hospital between 15.12.2013 and 15.03.2014. After the primary evaluation, standard 12 cores transrectal ultrasonography prostate biopsy was performed by the clinician to the appropriate patients with total prostate specific antigen (PSA) values ranging between 2.5-10 ng/mL. A sarcosine measurement with colorimetric and fluorometric principles was performed on patients’ urine samples taken before the prostate biopsy, following the prostate massage. Results: Statistically significant negative correlation in malignant group and positive correlation in benign group were found between percentage change in PSA values and fluorometric sarcosine measurements (r=-0.418; p=0.042; p<0.05 / r=0.318; p=0.013; p<0.05 respectively). Conclusion: The correlation between percentage change in PSA values and fluorometric sarcosine measurements can be used in patients with a grey zone PSA (such as PI-RADS 2-3 and low level PSA patients) in order to avoid unnecessary biopsies. [ABSTRACT FROM AUTHOR]

A straightforward distance-based paper analytical device (dPAD) was developed for monitoring sarcosine levels in human samples for the rapid diagnosis and prognosis of prostate cancer and related symptoms. This assay eliminates the need for the expensive horseradish peroxidase (HRP) enzyme by utilizing carbon nanodots (CDs) as a peroxidase-like nanozyme. The proposed dPAD sensor consists of a sample zone pre-deposited with sarcosine oxidase (SOx) and CDs, and a detection zone containing 3,3',5,5'-tetramethylbenzidine (TMB). When a solution containing sarcosine is added to the sample zone, hydroxyl radicals ( • OH) are produced through SOx oxidation and subsequent peroxidase catalysis by the CDs. The formed • OH radicals immediately flow to the detection zone via capillary force, where they oxidize TMB, resulting in a visible colour change from colourless to blue. Sarcosine quantification is effortlessly accomplished by measuring the distance of the blue colour in the detection zone. The developed dPAD offers a linear working range between 12.5 and 35.0 nmol L -1 (R 2  = 0.9959) and a detection limit (LOD) of 10.0 nmol L -1 . This covers the clinical range for urinary sarcosine determination, thereby suggesting no additional sample preparation or dilution is needed. The sensor shows high precision with the highest relative standard deviation (RSD) of 4.58% and demonstrates excellent selectivity with no observed interferences. Furthermore, recovery studies in human control urine samples ranged from 98.67 to 101.50%, with the highest RSD of 2.03%. Correspondingly, our dPAD method showed a great match with the performance of a commercial ELISA method for detecting sarcosine in human control serum. The sensor is more cost-effective, user-friendly, and accessible than previous methods. Overall, the proposed method represents a promising analytical tool for sarcosine quantification. The concept is also applicable for broader analytical applications in detecting other biomolecules., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Ketamine offers a fast-acting approach to relieving treatment-resistant depression, but its abuse potential is an issue of concern. As ketamine is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) ion channel blocker, modulation of NMDAR might be an effective strategy to counteract the abuse liability of ketamine and even to treat ketamine use disorder. This study evaluated whether NMDAR modulators that act on glycine binding sites can decrease motivation to obtain ketamine and reduce reinstatement to ketamine-seeking behavior. Two NMDAR modulators, D-serine and sarcosine were examined. Male Sprague–Dawley rats underwent training to acquire the ability to self-administer ketamine. The motivation to self-administer ketamine or sucrose pellets was examined under a progressive ratio (PR) schedule. The reinstatement of ketamine-seeking and sucrose pellet-seeking behaviors were assessed after extinction. The results showed that both D-serine and sarcosine significantly decreased the breakpoints for ketamine and prevented reinstatement of ketamine seeking. However, these modulators did not alter motivated behavior for sucrose pellets, the ability of the cue and sucrose pellets to reinstate sucrose-seeking behavior or spontaneous locomotor activity. These findings indicate that two NMDAR modulators can specifically reduce the measures of motivation and relapse for ketamine in rats, suggesting that targeting the glycine binding site of the NMDAR is a promising approach for preventing and treating ketamine use disorder.

A widely used herbicide for controlling weeds, glyphosate, is causing environmental pollution. It is necessary to remove it from environment using a cost-effective and eco-friendly method. The aims of this study were to isolate glyphosate-degrading bacteria and to optimize their degradative conditions required for bioremediation. Sixteen bacterial strains were isolated through enrichment and one strain, Rhodococcus soli G41, demonstrated a high removal rate of glyphosate than other strains. Response surface methodology was employed to optimize distinct environmental factors on glyphosate degradation of G41 strain. The optimal conditions for the maximum glyphosate degradation were found to have the NH4Cl concentration of 0.663% and glyphosate concentration of 0.115%, resulting in a maximum degradation of 42.7% after 7 days. Bioremediation analysis showed 47.1% and 40% of glyphosate in unsterile soil and sterile soil was removed by G41 strain after 14 days, respectively. The presence of soxB gene in G41 strain indicates that the glyphosate is degraded via the eco-friendly sarcosine pathway. The results indicated that G41 strain has the potential to serve as an in-situ candidate for bioremediation of glyphosate polluted environments. [ABSTRACT FROM AUTHOR]

L-Arginine:glycine amidinotransferase (AGAT) catalyzes the formation of L-homoarginine (hArg) and L-ornithine (Orn) from L-arginine (Arg) and L-lysine (Lys): Arg + Lys ↔ hArg + Orn; equilibrium constant KhArg. AGAT also catalyzes the formation of guanidinoacetate (GAA) and Orn from Arg and glycine (Gly): Arg + Gly ↔ GAA + Orn; equilibrium constant KGAA. In humans, pharmacological hArg is metabolized to Lys. Low circulating and low excretory concentrations of hArg are associated with worse outcomes and mortality in the renal and cardiovascular systems. The metabolism and pharmacology of hArg have been little investigated. In the present study, we investigated the effects of pharmacological hArg (i.p., 0, 20, 220, 440 mg/kg at time point 0 min) on amino acids homeostasis in a rat model of isoprenaline-induced takotsubo cardiomyopathy (i.p., 50 mg/kg at time point 15 min). We measured by gas chromatography-mass spectrometry free and proteinic amino acids, as well as the polyamines putrescine and spermidine in the heart, lung, kidney, and liver of ten rats sacrificed at various time points (range, 0 to 126 min). hArg administration resulted in multiple changes in the tissue contents of several free and proteinic amino acids, as well as in the putrescine-spermidine molar ratio, an indicator of polyamines catabolism. Our results suggest that Lys and Arg are major metabolites of pharmacological hArg. Kidneys and heart seem to play a major metabolic role for hArg. Circulating Lys does not change over time, yet there is a considerable interchange of free Lys between organs, notably kidney and heart, during the presence of isoprenaline in the rats (time range, 15 to 90 min). Antidromic changes were observed for KhArg and KGAA, notably in the heart in this time window. Our study shows for the first time that free hArg and sarcosine (N-methylglycine) are positively associated with each other. The acute effects of high-dosed hArg administration and isoprenaline on various amino acids and on AGAT-catalyzed reaction in the heart, lung, kidney, and liver are detailed and discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new cocrystal was prepared and its single crystal structure was resolved. • AUC of cocrystal reached 1.47 times greater than free 5-FU in ip injection. • The differences between PM and cocrystal hinted the supramolecular interactions. • Cocrystal enhanced cytotoxicity of 5-FU by induced methionine starvation. Pharmaceutical cocrystal is an emerging strategy not only to improve physicochemical properties, but also to generate synergistic effects. In this work, a novel cocrystal composed by 5-fluorouracil (5-FU) and sarcosine (SAR) was successfully assembled by wet powder grinding method. The cocrystal was characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and Raman spectra. The differences of 1H NMR spectroscopy between 5-FU/SAR physical mixture (PM) and cocrystal hinted the existence of supramolecular interactions between 5-FU and SAR in solid and solution. Bioavailability of cocrystal was increased than 5-FU. Most importantly, the weak interactions between 5-FU and SAR in cocrystal solution induced the superior cellar inhibition activity on 4T1 and BEL-7402 cells compared than 5-FU and PM. Cocrystal can interfere with the stability of methionine cycle and tetrahydrofolate (FH 4) level through the SAR-Gly-Met pathway, enhance the inhibition of thymidylate synthase (TS) compared to 5-FU, thereby interfering with cell cycle and inducing cell apoptosis. The results provided the novel strategy to develop the cocrystal drugs using bioactive amino acids as precursors to enhance the efficacy. [ABSTRACT FROM AUTHOR]

Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu 3 (PO 4) 2 :Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu 3 (PO 4) 2 :Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26–1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 μM to 60 μM, with a detection limit of 0.226 μM, and 'turn-on' colorimetric signals ranging from 0.18 μM to 60 μM, with a detection limit of 0.120 μM. Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes. A fluorescence and smartphone colorimetric sensing dual-mode multienzyme cascade based on oxidation-induced self-assembled nanoflowers for sarcosine's sensitive and selective detection. [Display omitted] • The simple synthesis method includes SOX as part of the enzyme-like catalyst. • The fluorescence was quenched by the SOX + Sar system, with activating nanozyme activity. • The generated H 2 O 2 has the effect of killing two birds with one stone for the cascade reaction system. • A chromogenic cotton swabs-based smartphone sensing system was developed for sarcosine analysis. [ABSTRACT FROM AUTHOR]

This article presents the development of a photothermal biosensing integrated with microfluidic paper-based analytical device (PT-μPAD) as a quantitative biosensor method for monitoring sarcosine in human control urine, plasma, and serum samples. The device utilizes gold nanoparticles (AuNPs) as both a peroxidase-like nanozyme and a photothermal substrate to enable sarcosine detection. In our PT-μPAD, hydrogen peroxide (H 2 O 2) is generated through the oxidation of sarcosine by a sarcosine oxidase (SOx) enzyme. Subsequently, the H 2 O 2 flows through the paper microchannels to the detection zone, where it etches the pre-deposited AuNPs, inducing a temperature change upon exposure by a 532 nm laser. The temperature variation is then measured using a portable and inexpensive infrared thermometer. Under optimized conditions, we obtained a linear range between 10.0 and 40.0 nmol L−1 (R2 = 0.9954) and a detection limit (LOD) of 32.0 pmol L−1. These values fall within the clinical range for sarcosine monitoring in prostate cancer diagnostics in humans. Moreover, our approach exhibits high selectivity without interfering effects. Recovery studies in various human control samples demonstrated a range of 99.05–102.11 % with the highest RSD of 2.25 %. The PT-μPAD was further validated for sarcosine determination in human control urine and compared with a commercial ELISA assay, revealing no significant difference between these two methods at a 95 % confidence level. Overall, our proposed sarcosine biosensor is well-suited for prostate cancer monitoring, given its affordability, sensitivity, and user-friendliness, even for unskilled individuals. Moreover, this strategy has promising prospects for broader applications, potentially detecting various biomarkers as a point-of-care (POC) diagnostic tool. [Display omitted] • We report the application of photothermal biosensing-based μPADs for sarcosine monitoring. • AuNPs application on μPADs is utilized as a peroxidase-like nanozyme and a photothermal substrate. • High sensitivity with a detection limit of 32.0 pg mL−1 is obtained. • The technique is faster than the same assay in the solution phase. • The analytical characteristic is well-suited for sarcosine detection in the clinical relevance. [ABSTRACT FROM AUTHOR]

Screen-printing technology is a game changer in many fields including electrochemical biosensing. Two-dimensional nanomaterial MXene Ti3C2Tx was integrated as a nanoplatform to immobilise enzyme sarcosine oxidase (SOx) onto the interface of screen-printed carbon electrodes (SPCEs). A miniaturised, portable, and cost-effective nanobiosensor was constructed using chitosan as a biocompatible glue for the ultrasensitive detection of prostate cancer biomarker sarcosine. The fabricated device was characterised with energy-dispersive X-ray spectroscopy (EDX), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Sarcosine was detected indirectly via the amperometric detection of H2O2 formed during enzymatic reaction. The nanobiosensor could detect sarcosine down to 7.0 nM with a maximal peak current output at 4.10 ± 0.35 × 10−5 A using only 100 µL of a sample per measurement. The assay run in 100 μL of an electrolyte showed the first linear calibration curve in a concentration window of up to 5 μM with a slope of 2.86 μA·μM−1, and the second linear calibration curve in the range of 5–50 μM with a slope of 0.32 ± 0.01 μA·μM−1 (R2 = 0.992). The device provided a high recovery index of 92.5% when measuring an analyte spiked into artificial urine, and could be used for detection of sarcosine in urine for at least a period of 5 weeks after the preparation.

Sarcosine level in serum is of important clinical significance in distinguishing prostate cancer. This work depicts an amperometric sarcosine biosensor with good anti-interference performance by electro-codepositing manganese phosphate, 3,4-ethylenedioxythiophene (EDOT) and indole-6-carboxylic acid (IA) on the glass carbon electrode. The prepared sarcosine biosensor has a wide linear detection range (1-55 µM) with a low detection limit of 0.11 µM. This work provides an antiinterference approach by controlling the surface charge density of the biosensor to sarcosine sensing, which has great potential to be used as point of care testing (POCT) device for the rapid detection of prostate cancer biomarkers. [ABSTRACT FROM AUTHOR]