Sarcosine Research Articles

Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial

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.

Effect of Micellar Morphology on the Temperature-Induced Structural Evolution of ABC Polypeptoid Triblock Terpolymers into Two-Compartment Hydrogel Network.

We investigated the temperature-dependent structural evolution of thermoreversible triblock terpolypeptoid hydrogels, namely poly(N-allyl glycine)-b-poly(N-methyl glycine)-b-poly(N-decyl glycine) (AMD), using small-angle neutron scattering (SANS) with contrast matching in conjunction with X-ray scattering and cryogenic transmission electron microscopy (cryo-TEM) techniques. At room temperature, A100M101D10 triblock terpolypeptoids self-assemble into core-corona-type spherical micelles in aqueous solution. Upon heating above the critical gelation temperature (T gel), SANS analysis revealed the formation of a two-compartment hydrogel network comprising distinct micellar cores composed of dehydrated A blocks and hydrophobic D blocks. At T ≳ T gel, the temperature-dependent dehydration of A block further leads to the gradual rearrangement of both A and D domains, forming well-ordered micellar network at higher temperatures. For AMD polymers with either longer D block or shorter A block, such as A101M111D21 and A43M92D9, elongated nonspherical micelles with a crystalline D core were observed at T < T gel. Although these enlarged crystalline micelles still undergo a sharp sol-to-gel transition upon heating, the higher aggregation number of chains results in the immediate association of the micelles into ordered aggregates at the initial stage, followed by a disruption of the spatial ordering as the temperature further increases. On the other hand, fiber-like structures were also observed for AMD with longer A block, such as A153M127D10, due to the crystallization of A domains. This also influences the assembly pathway of the two-compartment network. Our findings emphasize the critical impact of initial micellar morphology on the structural evolution of AMD hydrogels during the sol-to-gel transition, providing valuable insights for the rational design of thermoresponsive hydrogels with tunable network structures at the nanometer scale.

Selective pharmaceutical sensitization design based on amino acid metabolism: 5-fluorouracil-sarcosine cocrystal prepared by wet powder grinding method

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 (FH4) 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.

Smartphone-assisted portable paper-based biosensors for rapid and sensitive detection of biomarkers in urine

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 H2O2.

Paper-based enzyme-linked biosensor combined with smartphone for simultaneous colorimetric sensing of xanthines and sarcosine

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 H2O2, 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.

The cocrystals of 3,4-dihydroxyphenylactic acid: Improved phase stability and reduced hygroscopicity

Cocrystal technology is a collaborative strategy for improving the physicochemical properties of active pharmaceutical ingredients. To overcome the obstacles of phase instability and high hygroscopicity of 3,4-dihydroxyphenylactic acid (DHPAA), three new cocrystals of DHPAA with nicotinamide (NIC), caprolactam (CPR) and sarcosine (SAR) were designed and synthesized for the first time, which were characterized using single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and infrared spectroscopy technologies. The results of stability test and hygroscopicity study demonstrated that DHPAA−NIC, DHPAA−CPR and DHPAA−SAR exhibited a remarkable improvement in the phase stability of DHPAA, meanwhile, DHPAA−NIC and DHPAA−CPR also displayed reduced hygroscopicity compared to DHPAA. This study can provide new directions of improving the druggability of DHPAA through cocrystallization.

An intelligent ratiometric fluorescent assay based on MOF nanozyme-mediated tandem catalysis that guided by contrary logic circuit for highly sensitive sarcosine detection and smartphone-based portable sensing application

As the well-known test-indicator for early prostate cancer (PCa), sarcosine (SA) is closely related to the differential pathological process, which makes its accurate determination increasingly significant. Herein, we for the first time expanded the peroxidase (POD)-like property of facile-synthesized Zn-TCPP(Fe) MOF to fluorescent substrates and exploited it to ratiometric fluorescent (RF) sensing. By harnessing the effective catalytic oxidation of MOF nanozyme toward two fluorescent substrates (Scopoletin, SC; Amplex Red, AR) with contrary changes, and target-responsive (SA + SOx)/MOF/(SC + AR) tandem catalytic reaction, we constructed the first MOF nanozyme-based RF sensor for the quantitative determination of SA. Superior to previous works, the operation of this RF sensor is under the guidance of AND-(AND^NAND) contrary logic circuit. The dual-channel binary output changes (from 1/0 to 0/1) not only enable the intelligent logical recognition of SA, bringing strengthened reliability and accuracy, but also manifest the proof-of-concept discrimination of PCa individuals and healthy ones. Through recording the fluorescence alterations of SC (F465) and AR (F585), two segments of linear relationships between ratiometric values (F585/F465) and varied contents of SA are realized successfully. The LOD for SA could reach to as low as 39.98 nM, which outperforms all nanozyme-originated SA sensors reported till now. Moreover, this sensor also demonstrates high selectivity and satisfactory performance in human serum samples. Furthermore, the portable sensing of SA is realized under the assistance of smartphone-based RGB analysis, demonstrating the potential of point-of-care diagnostics of PCa in the future.

Fluorescence and colorimetric dual-mode multienzyme cascade nanoplatform based on CuNCs/FeMn-ZIF-8/PCN for detection of sarcosine.

It is critical to develop a highly efficient and sensitive method for detecting the biomarker sarcosine (SA) of prostate cancer due to its importance for men's health. In our work, a fluorescence (FL) and colorimetric dual-mode multienzyme cascade nanoplatform for SA detection was designed and constructed. CuNCs/FeMn-ZIF-8/PCN nanocomposites with high FL properties and peroxidase-like activity were successfully prepared by encapsulating copper nanoclusters (CuNCs) into FeMn-ZIF-8 and then loaded onto P-doped graphitic carbon nitride (PCN). Furthermore, the nanocomposites served as carriers for the immobilization of sarcosine oxidase (SOX) to construct a high-efficiency dual-mode multienzyme cascade nanoplatform CuNCs/SOX@FeMn-ZIF-8/PCN for the detection of SA. The intermediate H2O2 generated in the cascade caused the FL quenching of nanocomposites and the discoloration of 3,3',5,5'-tetramethylbenzidin. The linear ranges for SA detection in the dual-mode system were 1-100 μM (FL) and 1-200 μM (colorimetric), with detection limits of 0.34 and 0.59 μM, respectively. This nanoplatform exhibited notable repeatability, specificity, and stability, making it suitable for detecting sarcosine in real human urine samples. Therefore, this dual-mode multienzyme cascade nanoplatform would have a potential applicative prospect for detecting SA and other biomarkers in real clinical samples.

Wrinkled MXene-modified screen-printed electrodes for highly efficient sarcosine detection

MXenes are gaining immense attention owing to their robust conductivity, presence of favorable surface-functional groups and excellent hydrophilicity. Herein, a simple solution-based approach was adopted to functionalize few-layer thick MXene-Ti3C2Tx with chitosan (Chi) molecules, creating a stable electro-active screen-printed electrode (SPE) platform for the detection of sarcosine (SAR), a new biomarker for prostate cancer. In comparison to pristine MXene, the chitosan-functionalized Ti3C2Tx (MX-Chi/SPE) offered favorable surface functionalization for easy immobilization of sarcosine oxidase (SOx) enzymes, which led to the improved enzymatic oxidation of SAR. The detection mechanism relied upon the efficient reduction of enzymatically produced H2O2 over MX-Chi/SPE, enabling selective detection of SAR both in low (0.1–0.3 µM) and high (1.5–3.5 µM) concentration ranges, with an estimated limit of detection (LOD) values of 0.012 µM and 0.14 µM (S/N = 3), respectively. Due to its robust enzymatic configuration, the biosensor enabled selective detection of SAR even in the presence of interfering species like ascorbic acid, uric acid, and glucose. Furthermore, the biosensor demonstrated excellent signal repeatability and stability and effectively recovered spiked SAR levels (98–106%) from artificial urine samples. This approach demonstrated the successful integration of MXenes as redox-active materials in clinical biosensors with a simple electrode preparation procedure, which has the potential to be extended to other MXene compositions.

Portable and Rapid Dual-Biomarker Detection Using Solution-Gated Graphene Field Transistors in the Accurate Diagnosis of Prostate Cancer.

Prostate-specific antigen (PSA) is the common serum-relevant biomarker for early prostate cancer (PCa) detection in clinical diagnosis. However, it is difficult to accurately diagnose PCa in the early stage due to the low specificity of PSA. Herein, a new solution-gated graphene field transistor (SGGT) biosensor with dual-gate for dual-biomarker detection is designed. The sensing mechanism is that the designed aptamers immobilized on the surface of the gate electrodes can capture PSA and sarcosine (SAR) biomolecules and induce the capacitance changes of the electric double layers of SGGT. The limit of detections of PSA and SAR biomarkers can reach 0.01 fg mL-1 , which is three-to-four orders of magnitude lower than previously reported assays. The detection time of PSA and SAR is ≈4.5 and ≈13 min, which is significantly faster than the detection time (1-2h) of conventional methods. The clinical serum samples testing demonstrates that the biosensor can distinguish the PCa patients from the control group and the diagnosis accuracy can reach 100%. The SGGT biosensor can be integrated into the portable platform and the diagnostic results can directly display on the smartphone/Pad. Therefore, the integrated portable platform of the biosensor can distinguish cancer types through the dual-biomarker detection.

A promising modified polyvinyl chloride for adsorption of boron: Preparation, adsorption kinetics, isotherm, and thermodynamic studies

AbstractA new promising N‐methyl‐D‐glucamine modified polyvinyl chloride via methyl glycinate linker (PVC‐MG‐NMDG) was designed to extract boron from tourmaline ore from the Sikait area in the South Eastern Desert of Egypt, which assays 10.43% B2O3. Specifications for PVC‐MG‐NMDG composite were executed successfully utilizing sundry approaches, such as FT‐IR, XPS, GC–MS, TGA, BET, EDX, 13C‐NMR, 1H‐NMR, ICP‐OES, and XRD, which assure an acceptable synthesis of PVC‐MG‐NMDG. Optimized factors like pH, agitation time, primary boron concentration, composite dose, co‐ions, eluting agents, and temperature have been improved. At ambient temperature, pH 9, 10 min of agitation, and 0.0138 mol/L boron ions (150 ppm), the PVC‐MG‐NMDG composite has a 25 mg/g maximal uptake. The extraction‐distribution isotherm modeling suggests that the Langmuir model, with a theoretical value of 25.38 mg/g, more closely matches the practical value of 25 mg/g than the Freundlich model. The adsorption kinetics of boron ions by PVC‐MG‐NMDG were predicted with high accuracy using a pseudo‐second order kinetic model, yielding a theoretical retention capacity of 27.93 mg/g. The extraction process was predicted, as shown by thermodynamic calculations, exothermic, spontaneous, and optimal extraction at low temperature; the thermodynamic factors controlling ΔS (−0.04 kJ/mol), ΔH (−13.74 kJ/mol), and ∆G values rise from −1.82 kJ/mol at 298 K to −0.19 kJ/mol at 338 K. Boron ions can be eluted from the overloaded composite by 0.5 M H2SO4 with a 95% efficiency rate. It was established that PVC‐MG‐NMDG composite reveals a worthy separation factor to most co‐ions and gives a good separation power. Boric acid with a boron content of 17.23% and purity of 98.56% can be obtained through alkali fusion with NaOH flux and subsequent adsorption using a PVC‐MG‐NMDG composite.Highlights A New modified polyvinyl chloride (PVC‐MG‐NMDG) was successfully prepared. The characteristics of new composite were verified via different techniques. The new composite reached its maximum boron absorption of 25 mg/g at 25°C. The extraction as an exothermic, spontaneous process at low temperature. The new composite has been applied to a real sample of Sikait tourmaline ore.

Portable intelligent paper-based sensors for rapid colorimetric and smartphone-assisted analysis of hydrogen peroxide for food, environmental and medical detection applications

One of the effective approaches to safeguard human health is the rapid and sensitive identification of food additives, environmental pollutants, and disease markers. This study developed a portable intelligent paper-based sensor for point-of-care detection of hydrogen peroxide (H2O2) and sarcosine (SA) using smartphone colorimetric analysis, supplemented by UV-Vis verification. The paper-based sensor utilizes a chemical modification of conventional filter paper by immobilizing horseradish peroxidase (HRP) from the horseradish plant, achieved through boronate affinity and metal chelation techniques. For H2O2 detection, the sensor exhibited a linear range of 2–100 µmol L−1 and a limit of detection (LOD) of 1.0 µmol L−1. Similarly, a range of 2–400 μmol L−1 for SA detection and an LOD of 1.0 μmol L−1. The sensors were successfully employed for determining the H2O2 concentration in liquor samples, environmental water, and the amount of SA in urine. Significantly, the detection ranges of these sensors surpassed those of commercially available test strips. In summary, we first proposed enzyme-immobilized paper-based sensors for immobilizing HRP from plants to detect H2O2 and SA, which are intelligent, portable, fast, green, low-cost, highly sensitive, and selective, with broad application prospects in food analysis, environmental monitoring, and medical diagnostics.

Flower-like core-shell nanostructures based on natural asphalt coated with Ni-LDH nanosheets as an electrochemical platform for prostate cancer biomarker sensing

Flower-like core-shell nanostructures based on natural asphalt (NA) coated with nickel-layered double hydroxide nanosheets (Ni-LDH NSs) were synthesizedfor 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.

Manipulation of Morphology, Particle Size of Barium Sulfate and the Interacting Mechanism of Methyl Glycine Diacetic Acid.

In this paper, methyl glycine diacetic acid (MGDA) was found to have great influence on the morphology and particle size of barium sulfate. The effects of additive, concentration, value of pH and reaction temperature on the morphology and particle size of barium sulfate were studied in detail. The results show that the concentration of reactant and temperature have little effect on the particle size of barium sulfate. However, the pH conditions of the solution and the dosage of MGDA can apparently affect the particle size distribution of barium sulfate. The particle size of barium sulfate particles increases and the morphology changes from polyhedral to rice-shaped with the decreasing of the dosage of MGDA. In solution with higher pH, smaller and rice-shaped barium sulfate was obtained. To investigate the interacting mechanism of MGDA, the binding energy between MGDA and barium sulfate surface was calculated. It was found that the larger absolute value of the binding energy would result in stronger growth inhibition on the crystal face. Finally, the experimental data and theoretical calculations were combined to elucidate the interacting mechanism of the additive on the morphology and particle size of barium sulfate.

Preparation and physical characterization of Methotrexate encapsulated poly (n-methyl glycine) microspheres for the Rheumatoid arthritis treatment option

AimsThis research aimed to prepare and physically characterize methotrexate-encapsulated poly (n-methyl glycine) microspheres as a treatment option for rheumatoid arthritis. BackgroundRheumatoid arthritis is an autoimmune disease that leads to cartilage destruction, synovial joint inflammation, and bacterial joint/bone infections. Methotrexate (MTX), commonly used in rheumatoid arthritis (RA), has severe adverse effects. Therefore, a reliable drug delivery system is required to control the release of Methotrexate during the treatment of Rheumatoid arthritis. ObjectiveThe primary goal of this study was to develop and characterise methotrexate-loaded polysarcosine microspheres (MTX-PSar Microspheres), as well as to examine their physical characteristics, pharmacodynamics, and anti-rheumatic study effects. MethodMethotrexate (MTX) loaded Polysarcosine (PSar) Microsphere was developed using Mannitol, Magnesium hydroxide, Dichloromethane, Aqueous polyvinyl alcohol and Chitosan hydrochloride. The MTX-PSar Microsphere was developed by w/o/w multiple emulsions method in the current study to reduce inflammation and disease progression/joint stiffness caused by Rheumatoid Arthritis. FTIR, HPLC, XRD, DSC, and SEM were used to evaluate the physical properties of MTX-PSar Microspheres. ResultThe physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and X-Ray Diffraction have shown that drug encapsulated in the microparticles and lost its crystalline nature. The particle size, entrapment efficacy, reported in the range of 10–20 µm, 86.37 ± 0.65 %. Even after one month, the microsphere’s particle size maintained its spherical shape In-vitro drug release, pharmacodynamics study shows good anti-rheumatic study effects. ConclusionThe MTX-PSar Microsphere is a good option for treating RA despite the lack of in vivo action. OtherIt is hoped that in future studies, Methotrexate-loaded polysarcosine microspheres (MTX-PSar Microsphere) will be used to conjugate ligands, and hence active targeting in rheumatoid arthritis would be possible.

Fabrication of an electrochemical aptasensor for the determination of sarcosine based on synthesized CuCo2O4 nanosheets.

Sarcosine (SRN) detection in body fluids is related to the diagnosis of prostate cancer. However, the development of SRN biosensors has been limited due to the low concentration of SRN in body fluids. Here, a new electrochemical strategy for selective and accurate determination of SRN in urine samples is reported. CuCo2O4 nanosheets (CuCo2O4 NSs) have been synthesized and used as a new platform in the design of efficient electrochemical aptasensors for prostate cancer diagnosis. As far as we know, CuCo2O4 NSs have not been used so far in electrochemical aptasensor design. The presence of CuCo2O4 NSs on the electrode surface as a platform improves the conductivity and surface area. Therefore, it can be very effective in improving the diagnostic performance of the electrochemical aptasensor. The linear concentration range and limit of detection (LOD) for this strategy were calculated to be 1 pM- 8 μM and 350 fM, respectively.

Sarcosine (glycine transporter inhibitor) attenuates behavioural and biochemical changes induced by ketamine, in the rat model of schizophrenia

Schizophrenia is a neurological disorder that alters the behavior and affects the quality of life of a patient. It is characterized by hallucinations, disorganized behavior, cognitive dysfunction, hyperlocomotion, and loss of the reward system. Schizophrenia constitutes three symptoms' domains, viz. positive, negative and cognitive. Typical and atypical antipsychotics do not fully resolve all the symptoms' domains thus paving the way to the genesis of the glutamatergic hypothesis, i.e. N-methyl-D-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Positive modulation of NMDA receptors by enhancing co-agonist, glycine effect is proposed to produce a therapeutic effect in schizophrenia. Hence, sarcosine (N-methyl glycine), natural amino acid, and a glycine transporter inhibitor (GlyT-1) which also acts on NMDA receptors were used in the present study. The present study unravels the role of sarcosine in the attenuation of ketamine-induced three symptom domains in a rat model through modulation of oxidative stress, mitochondrial dysfunction, and neuroinflammatory pathways. The animal model of schizophrenia was established by injecting ketamine intraperitoneal (ip) at a 30mg/kg dose for 10 consecutive days, after which sarcosine (300, 600mg/kg, ip) as a treatment was given for 7days followed by behavioral, biochemical, molecular, and histopathological analysis. It was revealed that sarcosine reversed ketamine-induced behavioral impairments. Moreover, sarcosine ameliorated oxidative and nitrosative stress, mitochondrial dysfunction, and neuroinflammation and showed protective effects in histopathological examination by hematoxylin and eosin staining. Hence, conclusively, sarcosine was regarded to attenuate the behavioural symptoms of schizophrenia by alleviating oxidative stress, neuroinflammation, and mitochondrial dysfunction established by the ketamine.

Different Behavior of 2-Substituted 3-Nitro-2H-chromenes in the Reaction with Stabilized Azomethine Ylides Generated from α-Iminoesters.

The AgOAc-catalysed reaction of 3-nitro-2-phenyl-2H-chromenes with stabilized azomethine ylides generated from the imines based on methyl glycinate and arylaldehydes leads to a mixture of endo and endo' isomers of the corresponding chromeno[3,4-c]pyrrolidines in a ratio of 2.0-2.3:1 in 85-93% total yields as a result of a Michael addition/Mannich reaction sequence. In a similar reaction involving 2-trifluoromethyl-3-nitro-2H-chromenes, only endo chromeno[3,4-c]pyrrolidines are formed in 85-94% yields. 3-Nitro-2-(trichloromethyl)-2H-chromenes under the same conditions react with these azomethine ylides to give the corresponding Michael adducts as individual anti-isomers with the cis,trans-configuration of the chromane ring in 40-67% yields. Some 4-CF3-substituted chromano[3,4-c]pyrrolidines exhibited high cytotoxic activity against HeLa human cervical carcinoma cells.

The discovery of new cocrystals of 5-fluorocytosine using amine–carboxylate supramolecular synthon

Supramolecular synthon strategy is an often-employed principle to guide the discovery of novel pharmaceutical cocrystals. The amine–carboxylate (N–H···―OOC) intermolecular interaction has been confirmed as a member of the supramolecular toolbox, and a cocrystal of 5-fluorocytosine (FC) with L-proline (FC–L-PRO) containing this heterosynthon was previously harvested. Herein, two new cocrystals of FC with sarcosine (SAR) or dimethylglycine (DMG) were successfully screened out. Similar to FC–L-PRO, the N–H···―OOC synthon presents as the most important hetero-molecular interaction between FC and SAR/DMG in their crystal structures. And the FC molecular ribbons via homo-molecular N–H⋯N and N–H⋯O hydrogen bonds were observed in all of the cocrystal structures, which also exist in the structure of FC. Theoretical calculations show that the formations of FC–L-PRO and FC–DMG are thermodynamically favorable. While for FC–SAR–MeOH, the calculated result is not applicable. The coformer competitive experiments reveal that FC–L-PRO and FC–DMG have similar relative stability and FC–SAR–MeOH is the relative unstable form. These cocrystals exhibit weakened physical stability under high humidity condition (75% RH), then should be stored in controlled humidity conditions (≤50% RH). Additionally, FC–L-PRO demonstrates reduced intrinsic dissolution rate (IDR) in pH 1.2 medium (simulated gastric fluid), which may provide positive contribution to alleviate its toxic side effects.

Novel highly selective fluorescence sensing strategy for Mercury(Ⅱ) in water based on nitrogen-doped carbon quantum dots

In this work, a fluorescent signal-closing probe of nitrogen-doped carbon quantum dots (NCQDs) was developed for quantitative detection of mercury ions (Hg2+). In this detection system, the NCQDs with high quantum yield (QY, 63.80 %) were synthesized via simple hydrothermal method with Methyl Glycine Diacetic acid Trisodium Salt (MGDA) and m-phenylenediamine (MPD) as carbon and nitrogen sources. The NCQDs have a typical surface structure and exceptional fluorescence stability, and their fluorescence zones are centered on excitation wavelengths of 440 nm and emission wavelengths of 510 nm. Under optimal conditions, the NCQDs have outstanding anti-interference ability to various ions and high selectivity to mercury ions. The fluorescence intensity of the detection system is weakened due to the generation of non-fluorescent groups caused by the static quenching effect. The fluorescence quenching efficiency shows a fascinating linear relationship with Hg2+ ions at 0–100 μM (y = 0.0051x-0.015, R2 = 0.9943), and the detection limit is 0.9 μM. Acute toxicity test shows that NCQDs have low toxicity and little harm to environment. The detection system can be used for the quantification of mercury ions in environmental water samples, and the recovery rate is between 99.64 % and 103.43 %, indicating that it is a simple and economical fluorescence detection method.