Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthenia Gravis.

AIMS: The study aims to evaluate the efficacy of low dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). METHODS: This is a single-center, retrospective study. A total of 10 patients with MuSK-MG were admitted to the Department of Neurology, First Hospital, Shanxi Medical University, between April 2021 to April 2023. Of them, 9 patients had been treated with low dose RTX (500 mg every 6 month) and recruited in this study. The clinical information, including the severity before and after RTX treatment, were collected from the medical records. Clinical effectiveness was assessed by Myasthenia Gravis Foundation of America (MGFA)-postintervention status (PIS), MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), dosage of steroid at the end of follow up. RESULTS: All nine patients showed clinical improvement at the final follow-up after low-dose RTX treatment. The mean dose of prednisolone decreased significantly from 50 mg at baseline to 18.33 mg at the last follow-up (z = -3.417, p = 0.001). The administration of low-dose RTX treatment led to significant improvements in ADL levels (Z = -2.675, P < 0.01), QMG score levels (Z = -2.371, P < 0.05) and QOL-15r levels (Z = -2.547, P < 0.01) at last visit. CONCLUSION: Low-dose RTX is effective for treating MuSK-MG patients. Longer-term follow-up and larger-scale studies are needed to provide further evidence.

Ruta graveolens: Boost Melanogenic Effects and Protection against Oxidative Damage in Melanocytes.

Vitiligo, an acquired depigmentation disorder, is characterized by the loss of functional melanocytes and epidermal melanin. In recent years, research has focused on promoting melanin biosynthesis and protecting melanocytes to reduce stress-related damage for the purpose of applying it to vitiligo treatment. Ruta graveolens L. has been utilized as a medicinal herb in diverse traditional medicine systems to address conditions like vitiligo. In this investigation, we isolated and purified 16 unique alkaloid compounds from the chloroform extracts of R. graveolens, encompassing a new quinoline alkaloid and several recognized compounds. Bioactivity analysis showed that compound 13, an alkaloid derived from R. graveolens, promotes melanin production while protecting PIG3V melanocytes against 4-tert-butylphenol (4-TBP)-induced oxidative damage by downregulating endoplasmic reticulum (ER) stress and pro-inflammatory cytokines through interleukin-6 (IL-6) regulation. Additionally, the compound suppressed the expression of Bip, IRE1, p-IRE1, and XBP-1 proteins, suggesting a potential antioxidant function. These findings suggest that compound 13 isolated from R. graveolens can augment melanogenesis in melanocytes, reduce endoplasmic reticulum (ER) stress, and ameliorate vitiligo exacerbation. The melanogenic activity observed in the chloroform fraction emphasizes R. graveolens's potential as a novel therapeutic target for vitiligo treatment, warranting further exploration in future studies.

Co-assembly of graphene/polyoxometalate films for highly electrocatalytic and sensing hydroperoxide.

Graphene oxide (GO) films mixed with polyethylenimine (PEI) were prepared by a layer-by-layer assembly (LBL) method, in which the GO component is then converted to reduced GO (rGO) in situ through an electron transfer interaction with a polyoxometalate (POM) that is assembled on the outer surface. With this, devices were manufactured by spreading composite films of (PEI/rGO)n-POM with different numbers of PEI/rGO layers on ITO substrates. Cyclic voltammetry (CV) reveals that the catalytic activity for H2O2 of (PEI/rGO)n-POM films was significantly higher than that of similar films of (PEI/GO)n/PEI/POM manufactured LBL with the same number of layers, although the catalyst POM content of (PEI/rGO)n-POM was only half that of (PEI/GO)n/PEI/POM. The catalytic activity of (PEI/rGO)n-POM films first increases and then decreases as the number of PEI/rGO layers increases. The result shows that (PEI/rGO)3-POM films with three PEI/rGO layers exhibit the highest efficiency. Amperometric measurements of the (PEI/rGO)3-POM films showed improved current response, high sensitivity, wide linear range, low detection limit, and fast response for H2O2 detection. The enhanced catalytic property of (PEI/rGO)n-POM films is attributed to the electron transfer interaction and electrostatic interaction between POM and rGO.

Bimetallic metal-organic frameworks-based ratiometric fluorescence sensor for the quantitative detection of thiram in fruits samples.

The identification of residual thiram (Tr) in foods is vital in view of its harmful effects on human health. Herein, a ratiometric fluorescence sensor (I435/I590) based on rhodamine B/NH2-MIL-53(Al0.75Fe0.25) was constructed for the detection of Tr. Interestingly, the probe RhB/NH2-MIL-53(Bim) assisted by Cu2+ could rapidly and sensitively recognize Tr with a low detection limit of 0.11 µg/mL in 10 min. The fluorescence sensing mechanism was investigated using fluorescence spectra, UV-Vis absorption spectra, the fluorescence lifetime and quantum yield. The results showed that the excellent sensing performance was attributed to fluorescence resonance energy transfer, electrostatic interaction, and photoinduced electron transfer. In addition, the practical application of this platform showed acceptable relative recoveries for Tr (84.03-107.81 %), and precisions were also achieved (relative standard deviation ≤ 8.69 %, n = 3). These results show that the presented herein can be applied to monitor the Tr content in real fruit samples.

An ultralow concentration of Al-MOFs for turn-on fluorescence detection of aflatoxin B1 in tea samples.

A turn-on fluorescent sensing platform based on an ultralow concentration of Al-metal organic frameworks for the detection of aflatoxin B1 has been developed for the first time. This fluorescence turn-on sensor exhibits the largest fluorescence enhancement (or quenching) constant value of 179404 M-1 among all luminescence-based chemical sensors reported till date. Moreover, the sensor afforded a rapid detection of aflatoxin B1, with a linear response in the concentration range of 0.05-9.61 µM and a low detection limit of 11.67 ppb. Additionally, the fabricated sensor showed good repeatability, reproducibility, stability, and selectivity. Most importantly, the practical application of this sensor has been demonstrated by detecting aflatoxin B1 in complex tea samples with low relative standard deviation (≤7.72%; n = 3) and satisfactory recoveries. In summary, the proposed method has great potential as a simple, sensitive and selective strategy for monitoring aflatoxin B1 in food samples.

Chemical constituents of Ruta graveolens L. and their melanogenic effects and action mechanism.

Ruta graveolens L. has been widely used to treat various skin ailments, especially vitiligo. In this study, we isolated a new furanocoumarin named Rutagrarin (1) along with 14 known compounds (2-15) from the aerial parts of R. graveolens and elucidated their chemical structures via various spectroscopy. We found that compound 5 promoted melanogenesis and tyrosinase activity in B16 cells. Further investigation on underlying mechanisms revealed that compound 5 activated the transcription of microtia-related transcription factors and promoted the production of melanin in B16 cells via the Akt/GSK-3ß/ß-catenin pathway. Therefore, we confirmed the traditional efficacy of R. graveolens and speculated that compound 5 could be used as a natural drug to treat vitiligo.

Synthesis of pyranochalcone derivatives and their inhibitory effect on NF-κB activation.

In an effort to identify novel inhibitors of nuclear factor kappa B (NF-κB), twenty five pyranochalcone derivatives were synthesized and evaluated for their in vitro activities against TNF-α induced NF-κB inhibition in HEK293T cells. Among all of these derivatives, several displaying the same acrylate moiety on the B ring exhibited potent inhibition, with IC50 values ranging from 0.29 to 10.46 µM. A functional study of the most potent of these compounds, designated 6b, revealed that it significantly suppressed the transcriptional expression of inflammatory factor IL-1ß in lipopolysaccharide-induced RAW 264.7 macrophages, and also mildly inhibited CCL2, IL6 and TNF-α. In addition, compound 6b was found to inhibit IL-1ß released in LPS-induced BMDM cells. This study demonstrates that the inhibitory effect of 6b on LPS-stimulated inflammatory mediator production in the mouse macrophage cell line RAW 264.7 correlates with the suppression of the NF-κB and MAPK signaling pathways.

Evaluation of Clinical Features and Stroke Etiology in Patients with Bilateral Middle Cerebellar Peduncle Infarction.

OBJECTIVE: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). METHODS: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. RESULTS: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. CONCLUSION: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery.

Electrochemical Reduction-Assisted In Situ Fabrication of a Graphene/Au Nanoparticles@polyoxometalate Nanohybrid Film: High-Performance Electrochemical Detection for Uric Acid.

Nanohybrid films had attracted much attention owning to the enhancement of catalytic activity. However, the fabrication time took hours to days, no matter if it was the preparation of nanohybrids or the assembly process. Furthermore, the catalytic efficiency of the nanohybrid film still remained to improve. In this paper, a reduced graphene oxide (rGO)/gold nanoparticles (Au NPs)@polyoxometalate (POM) nanohybrid film was successfully fabricated by combining electrodeposition and electrochemical reduction in situ processes. The assembly process involving no organic or polymer linker molecules [except for a precursor poly(ethylenimine) (PEI) coating for indium tin oxide (ITO)] can be completed within 1 h. The reduced POM K6[P2W18O62]·19H2O (P2W18) was employed as reducing agents and bridging molecules for rGO and Au nanoparticles and the encapsulating molecules for the Au nanoparticles. The most interesting one is the {rGO/Au@P2W18} modified electrode loading only the monolayer catalyst of Au@P2W18 and exhibiting comparable, even better electrochemical detection performance toward uric acid than other sensors with three to eight layers of the catalyst. The amperometric detection displayed a great sensitivity, lower detection limit, wide linear range, good long-time stability, superior selectivity, and reproducibility. The enhanced catalytic property may attribute to the improved conductivity of the film without organic or polymer linker molecules (except for a precursor PEI coating) and the electron transfer in the process of film fabrication.

Attapulgite modified magnetic metal-organic frameworks for magnetic solid phase extraction and determinations of benzoylurea insecticides in tea infusions.

Herein, we developed a novel magnetic solid phase extraction method based on attapulgite-modified magnetic metal-organic frameworks (ATP@Fe3O4@ZIF-8), and this method could be used for the determination of benzoylureas when it was coupled with high-performance liquid chromatography. The established method was validated in terms of linearity (2.5-500 µg L-1, with correlation coefficient (R2) > 0.9994), accuracy (with satisfactory recovery of 88.29-95.99%) and precision (with relative standard deviation (RSD) of less than 8%). In addition, the enrichment factors (EF) ranged from 63.6 to 72.2. Limit of detection (LOD) and limit of quantitation (LOQ) were 0.7-3.2 µg L-1 and 2.3-10.7 µg L-1, respectively. Moreover, there was hardly any noticeable loss of the extraction efficiency when this extraction method undergoes five cycles. Finally, this method was successfully used for the determination of six benzoylureas in different tea infusions and the determined relative recoveries ranged from 78.8 to 114.3%.

Isolation and Characterization of Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Polyphenolic Compounds From Dodonaea viscosa and Their Kinetic Analysis.

Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5-57.9 µM. Among them, viscosol (4) was found to be the most potent compound having IC50 13.5 µM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki) value of 4.6 µM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7, and 9 were found to be the most abundant metabolites in D. viscosa extract.

Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa.

Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1-8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1-5) and dihydroflavonols (6-8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50 = 1.9-8.2 µM) than α-glucosidase (IC50 = 2.2-78.9 µM). Mimulone (1) was the most effective against PTP1B with IC50 = 1.9 µM, whereas 6-geranyl-3,3',5,5',7-pentahydroxy-4'-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC50 = 2.2 µM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.

Facile preparation of graphene by high-temperature electrolysis and its application in supercapacitor.

Graphene is well known owing to its astonishing properties: stronger than diamond, more conductive than copper and more flexible than rubber. Because of its potential uses in industry, researchers have been searching for less toxicity ways to make graphene in large amount with lower cost. We demonstrated an efficient method to prepare graphene by high temperature electrolysis technique. High resolution scanning electron microscopy and raman spectroscopy were used to characterize the microstructure of graphene. Graphene was assembled into the supercapacitor and its performance of electrochemical capacitor was investigated by constant current charge and discharge, cyclic voltammetry and AC impedance. The results showed that the micro-morphology of the prepared graphene was multilayer and it was favorable when the electrolytic voltage was 1.5 V. When the current density is 1 mA/cm(2), the specific capacitance of the graphene supercapacitor can reach 78.01 F/g in 6 mol/L KOH electrolyte, which was an increase of 114% compared with 36.43 F/g of conventional KOH electrolyte.

Novel cyclic sulfonium-based ionic liquids: synthesis, characterization, and physicochemical properties.

A new series of ionic liquids composed of three cyclic sulfonium cations and four anions has been synthesized and characterized. Their physicochemical properties, including their spectroscopic characteristics, ion cluster behavior, surface properties, phase transitions, thermal stability, density, viscosity, refractive index, tribological properties, ion conductivity, and electrochemical window have been comprehensively studied. Eight of these salts are liquids at room temperature, at which some salts based on [NO(3)](-) and [NTf(2)](-) ions exhibit organic plastic crystal behaviors, and all the saccharin-based salts display relatively high refractive indices (1.442-1.594). In addition, some ionic liquids with the [NTf(2)](-) ion exhibit peculiar spectroscopic characteristics in FTIR and UV/Vis regions, whilst those salts based on the [DCA](-) ion show lower viscosities (34.2-62.6 mPa s at 20 degrees C) and much higher conductivities (7.6-17.6 mS cm(-1) at 20 degrees C) than most traditional 1,3-dialkylimidazolium salts.

Physicochemical properties of nitrile-functionalized ionic liquids.

A series of ionic liquids (ILs) based on nitrile-functionalized imidazolium, pyridinium, and quaternary ammonium as cations and chlorides and tetrafluoroborate, hexafluorophosphate, dicyanamide, and bis(trifluoromethanesulfonyl)imide as anions have been prepared and characterized. The physicochemical properties such as spectroscopic, thermal, solubility, surface, electrochemical, tribological, and toxic properties were comparatively studied. The results showed that the incorporation of a CN group to cations could result in remarkable changes in these properties. The reason resulting in such remarkable differences in the properties may be attributed to the conformational changes in the imidazolium groups caused by the interaction between the CN group with other neighboring cations or anions and the enhancement in hydrogen-bonding interactions due to the incorporation of a CN group.

Investigation of physicochemical properties of lactam-based Brønsted acidic ionic liquids.

Novel lactam-cation-based Brønsted acid ionic liquids (ILs) were prepared through a simple and atom-economic neutralization reaction between a lactam, such as caprolactam and butyrolactam, and a Brønsted acid, HX, where X is BF4-, CF3COO-, phCOO-, ClCH2COO-, NO3-, or H2PO4-. The density, viscosity, acidic scale, electrochemical window, temperature dependency of ionic conductivity, and thermal property of these ILs were measured and investigated in detail. The results show that protonated caprolactam tetrafluoroborate (CPBF) has a relatively strong acidity with -0.22 of Hammett acidic scale H0 and caprolactam trifluoroacetate (CPTFA) and pyrrolidonium trifluoroacetate (PYTFA) ILs possess very low viscosities, that is, 28 cP and 11 cP, respectively. An investigation of thermal property showed that a wide liquid range (up to -90 degrees C), moderate thermal stability (up to 249 degrees C for 10% of decomposition), and complex polymorphism were observed in these ILs. In comparison to imidazolium-cation-based ILs, the lactam-cation-based Brønsted acid ILs have a relatively lower cost, lower toxicity, and comparable ion conductivity and heat storage density (more than 200 MJ/m3). They have wide applicable perspectives for fuel cell devices, thermal transfer fluids, and acid-catalyzed reaction media and catalysts as replacements of conventional inorganic acids.