Protective effect of cellulose and soluble dietary fiber from Saccharina japonica by-products on regulating inflammatory responses, gut microbiota, and SCFAs production in colitis mice.

This study aimed to investigate the physicochemical properties of soluble dietary fiber (SDF) and cellulose enriched in Saccharina japonica by-products and to evaluate their anti-colitis effects. The water-holding capacity (WHC), swelling capacity (SC), cation exchange capacity (CEC), and antioxidant properties of SDF were superior to cellulose. The ΔH of SDF and cellulose was 340.73 J/g and 134.56 J/g, and the average particle size of them was 43.858 µm and 97.350 µm. The viscosity of SDF was positively correlated with the content. SEM revealed that the microstructure of SDF was porous, whereas cellulose was folded. SDF contained seven monosaccharides such as mannuronic acid and mannose, while cellulose had a single glucose composition. It was also shown that both SDF and cellulose reversed the pathological process of colitis by inhibiting weight loss, preventing colon injury, balancing oxidative stress, and regulating the level of inflammation, with the optimal dose being 1.5 g/kg. The difference was that SDF inhibited the expression of NF-кB and TNF-α, while cellulose up-regulated the expression of PPAR-γ and IL-10. Additionally, SDF could more positively control the expression of ZO-1, whereas cellulose was superior in improving the expression of Occludin. Interestingly, SDF could restore the structure of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group to ameliorate ulcerative colitis (UC), whereas cellulose mainly regulated the abundance of norank_f_Muribaculaceae, Faecalibaculum, Bacteroides and unclassified_f__Lachnospiraceae. The production of short-chain fatty acids (SCFAs) was also found to be restored by SDF and cellulose. Overall, SDF and cellulose can be considered important dietary components for treating and preventing UC.

Bibliometric and visualization analysis of risk management in the doctor-patient relationship: A systematic quantitative literature review.

OBJECTIVES: This paper analyzed the research on risk management in the doctor-patient relationship (DPR) based on a systematic quantitative literature review approach using bibliometric software. It aims to uncover potential information about current research and predict future research hotspots and trends. METHODS: We conducted a comprehensive search for relevant publications in the Scopus database and the Web of Science Core Collection database from January 1, 2000 to December 31, 2023. We analyzed the data using CiteSpace 6.2.R2 and VOSviewer 1.6.19 software to examine the annual number of publications, countries/regions, journals, citations, authors, and keywords in the field. RESULTS: A total of 553 articles and reviews that met the criteria were included in this study. There is an overall upward trend in the number of publications issued; in terms of countries/regions, the United States and the United Kingdom are the largest contributors; Patient Education and Counseling is the most productive journal (17); Physician communication and patient adherence to treatment: a meta-analysis is the most cited article (1637); the field has not yet to form a stable and obvious core team; the analysis of high-frequency keywords revealed four main research directions: the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the keyword burst analysis revealed several shifts in the research hotspots for risk management in the DPR, suggesting that chronic disease management, is a future research direction for the continued development of risk management in the DPR. CONCLUSIONS: The visualization analysis of risk management literature in the DPR using CiteSpace and VOSviewer software provides insights into the current research status and highlights future research directions.

Extraction of heavy metals from copper tailings by ryegrass (Lolium perenne L.) with the assistance of degradable chelating agents.

Heavy metal contamination is an urgent ecological governance problem in mining areas. In order to seek for a green and environmentally friendly reagent with better plant restoration effect to solve the problem of low efficiency in plant restoration in heavy metal pollution soil. In this study, we evaluated the effects of three biodegradable chelating agents, namely citric acid (CA), fulvic acid (FA) and polyaspartic acid (PASP), on the physicochemical properties of copper tailings, growth of ryegrass (Lolium perenne L.) and heavy metal accumulation therein. The results showed that the chelating agent application improved the physicochemical properties of copper tailings, increased the biomass of ryegrass and enriched more Cu and Cd in copper tailings. In the control group, the main existing forms of Cu and Cd were oxidizable state, followed by residual, weak acid soluble and reducible states. After the CA, FA or PASP application, Cu and Cd were converted from the residual and oxidizable states to the reducible and weak acid soluble states, whose bioavailability in copper tailings were thus enhanced. Besides, the chelating agent incorporation improved the Cu and Cd extraction efficiencies of ryegrass from copper tailings, as manifested by increased root and stem contents of Cu and Cd by 30.29-103.42%, 11.43-74.29%, 2.98-110.98% and 11.11-111.11%, respectively, in comparison with the control group. In the presence of multiple heavy metals, CA, FA or PASP showed selectivity regarding the ryegrass extraction of heavy metals from copper tailings. PCA analysis revealed that the CA-4 and PASP-7 treatment had great remediation potentials against Cu and Cd in copper tailings, respectively, as manifested by increases in Cu and Cd contents in ryegrass by 90.98% and 74.29% compared to the CK group.

Crosstalk mitigation of a controllable annular auto-focusing vortex beam array in a turbulent atmosphere.

In this paper, we introduce a new type of controllable auto-focusing vortex beam array named annular quasi-Airy vortex beam array (QAVBA), which can reduce the crosstalk among different orbital angular momentum (OAM) modes of optical vortex. The effects of initial beam parameters of annular QAVBA and propagation conditions on the OAM mode propagation performance are investigated. The results indicate that the topological angle θ, the topological charge m, and the decay parameter α could manipulate the auto-focusing characteristics of annular QAVBA and regulate the crosstalk of OAM modes. The crosstalk among OAM modes increases with the turbulence strength. Interestingly, the annular QAVBA with obtuse topological angle is favorable for the OAM mode transmitting at far propagation distance or in strong atmospheric turbulence when the decay parameter α is large enough for the energy of annular QAVBA mainly concentrating on the main light ring. Our research provides a reference for optimizing the design of light sources and free-space optical communication system with annular QAVBA.

Ag(I) Ion-Concentration-Dependent Dynamic Mechanism of Thiolactic-Acid-Capped Gold Nanoclusters Revealed by Fluorescence Spectra and Two-Dimensional Correlation Spectroscopy.

Based on fluorescence spectroscopy, being combined with several spectral analysis techniques including principal component analysis (PCA), two-dimensional correlation spectroscopy (2D-COS), and moving window 2D-COS, the study disclosed the structural variations of gold nanoclusters capped by thiolactic acid (AuNCs@TLA) induced by Ag(I) ions. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were applied to monitor the morphology evolution of the surface and composition of the nanoclusters induced by Ag(I) ions. Several spectral components, centered at (790, 607) nm, (670, 590) nm, and (740, 670) nm were revealed by 2D-COS analysis, suggesting new luminescent species or groups were generated with the introduction of Ag(I) ions. A two-stage mechanism was revealed for the photoluminescence variations of AuNCs@TLA induced by Ag(I) ion. The first stage was characterized by the emission quench of 790 nm followed by the emerging emission of 607 nm, which was attributed to the anti-galvanic reaction; and the second stage featured by the noticeable growth of the emission's intensity around 670 nm as result of the AuNCs' size effect. The present study will attract more focuses on near-infrared (NIR)-emitted metal nanoclusters and promote their synthesis and utilities.

MXene-Stabilized VS2 Nanostructures for High-Performance Aqueous Zinc Ion Storage.

Aqueous zinc-ion batteries (AZIBs) based on vanadium oxides or sulfides are promising candidates for large-scale rechargeable energy storage due to their ease of fabrication, low cost, and high safety. However, the commercial application of vanadium-based electrode materials has been hindered by challenging problems such as poor cyclability and low-rate performance. To this regard, sophisticated nanostructure engineering technology is used to adeptly incorporate VS2 nanosheets into the MXene interlayers to create a stable 2D heterogeneous layered structure. The MXene nanosheets exhibit stable interactions with VS2 nanosheets, while intercalation between nanosheets effectively increases the interlayer spacing, further enhancing their stability in AZIBs. Benefiting from the heterogeneous layered structure with high conductivity, excellent electron/ion transport, and abundant reactive sites, the free-standing VS2/Ti3C2Tz composite film can be used as both the cathode and the anode of AZIBs. Specifically, the VS2/Ti3C2Tz cathode presents a high specific capacity of 285 mAh g-1 at 0.2 A g-1. Furthermore, the flexible Zn-metal free in-plane VS2/Ti3C2Tz//MnO2/CNT AZIBs deliver high operation voltage (2.0 V) and impressive long-term cycling stability (with a capacity retention of 97% after 5000 cycles) which outperforms almost all reported Vanadium-based electrodes for AZIBs. The effective modulation of the material structure through nanocomposite engineering effectively enhances the stability of VS2, which shows great potential in Zn2+ storage. This work will hasten and stimulate further development of such composite material in the direction of energy storage.

How traditional Chinese medicine can prevent recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography?

Common bile duct stones, as a type of cholelithiasis, are a benign biliary obstruction that easily acute abdominalgia, and Endoscopic Retrograde Cholangiopancreatography (ERCP) is usually the first choice for clinical treatment. However, the increasing recurrence rate of patients after treatment is troubling clinicians and patients. For the prevention of recurrence after ERCP, there is no guideline to provide a clear drug regimen, traditional Chinese medicine however has achieved some result in the treatment of liver-related diseases based on the "gut-liver-bile acid axis". On the basis of this, this article discusses the possibility of traditional Chinese medicine to prevent common bile duct stones (CBDS) after ERCP, and we expect that this article will provide new ideas for the prevention of recurrence of CBDS and for the treatment of cholelithiasis-related diseases with traditional Chinese medicine in future clinical and scientific research.

Cation Exchange in Colloidal Transition Metal Nitride Nanocrystals.

Transition metal nitride (TMN)-based nanostructures have emerged as promising materials for diverse applications in electronics, photonics, energy storage, and catalysis due to their highly desirable physicochemical properties. However, synthesizing TMN-based nanostructures with designed compositions and morphologies poses challenges, especially in the solution phase. The cation exchange reaction (CER) stands out as a versatile postsynthetic strategy for preparing nanostructures that are otherwise inaccessible through direct synthesis. Nevertheless, exploration of the CER in TMNs lags behind that in metal chalcogenides and metal phosphides. Here, we demonstrate cation exchange in colloidal metal nitride nanocrystals, employing Cu3N nanocrystals as starting materials to synthesize Ni4N and CoN nanocrystals. By controlling the reaction conditions, Cu3N@Ni4N and Cu3N@CoN core@shell heterostructures with tunable compositions can also be obtained. The Ni4N and CoN nanocrystals are evaluated as catalysts for the electrochemical oxygen evolution reaction (OER). Remarkably, CoN nanocrystals demonstrate superior OER performance with a low overpotential of 286 mV at 10 mA·cm-2, a small Tafel slope of 89 mV·dec-1, and long-term stability. Our CER approach in colloidal TMNs offers a new strategy for preparing other metal nitride nanocrystals and their heterostructures, paving the way for prospective applications.

Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets.

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/b-catenin signaling pathway / Rspo2-LGR4 agrava la progresión del carcinoma hepatocelular al activar la vía de señalización Wnt/beta-catenina

Background: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. Methods: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. Results: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. Conclusions: LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway. (AU)

Antecedentes: El receptor de acoplamiento de proteínas G de secuencia repetida 4 (LGR4), rico en leucina, juega un papel importante en la diferenciación de células madre, el desarrollo de órganos y el cáncer. Se desconoce si LGR4 afecta la progresión del carcinoma hepatocelular (HCC). El objetivo de este estudio es revelar el papel de LGR4 en el HCC. Métodos: Se recolectaron muestras clínicas de HCC para evaluar la expresión de LGR4 y su correlación con los resultados clínicos de HCC. Alterar los niveles de expresión de LGR4 en las células de HCC mediante métodos farmacológicos y genéticos y analizar el papel de LGR4 en la progresión del cáncer de hígado mediante mediciones in vivo e in vitro. El HCC fue inducido en ratones de tipo salvaje y con defectos de LGR4 con Nitrosamina de dietilo (DEN) y cloruro de carbono (CCl4), y los efectos de LGR4 sobre el HCC fueron detectados por evaluación histopatológica y determinación bioquímica. Resultados: La expresión de LGR4 está regulada en HCC, y su nivel de expresión está positivamente relacionado con el tamaño tumoral, la infiltración microvascular (MVI), la etapa de TNM y el grado de diferenciación patológica en pacientes con HCC. En el modelo de HCC de ratón inducido por DEN+CCl4, golpear bajo LGR4 inhibió efectivamente la progresión del HCC. El silencio de LGR4 inhibe la proliferación, migración, invasión, propiedades similares a las células madre y el efecto Warburg de las células HCC. Estos fenotipos son promovidos por el ligando endógeno roof slab-specific sponge 2 (Rspo2)de LGR4. El Rspo2 aumentó significativamente la translocación nuclear de la proteína beta-catenina, mientras que el inhibidor de la señalización Wnt/beta-cateninaIWR-1 revirtió su acción... (AU)

Influencing factors of sleep quality in pregnant: a structural equation model approach.

BACKGROUND: To describe the changes in the level of sleep quality during pregnancy among pregnant women in Urumqi; also to construct a structural equation model of the factors influencing the sleep quality of pregnant women, to analyze the path relationship between the influencing factors, and to take reasonable interventions to prevent and reduce the occurrence of sleep disorders among pregnant women. METHODS: 986 pregnant women who gave birth in Urumqi Maternal and Child Health Hospital and Urumqi Youai Hospital between August 2021 and May 2023 were selected. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Edinburgh Postpartum Depression Scale (EPDS) were used to assess the sleep, anxiety, and depression of pregnant women, Building a structural equation model based on AMOS 23.0 Tools. RESULTS: The results of structural equation modeling showed that: basic characteristics, obstetrical characteristics, tocolysis, lifestyle, psychological had a direct effect on the PSQI, with path coefficients of 0.243, 0.106, 0.140, 0.174, 0.658, the corresponding T-values for each path are 4.585, 2.677, 2.578, 2.297, and 9.036. The indirect effect of basic characteristics, obstetric characteristics and lifestyle on PSQI was 0.123, 0.020, 0.027. CONCLUSIONS: The high incidence of sleep disorders in pregnant women and their close association with psychological symptoms in pregnant women should focus on screening and counseling regarding psychological disorders in pregnant women, thus improving the quality of sleep in pregnant women.

Effectiveness and safety of different catechol-o-methyl transferase inhibitors for patients with parkinson's disease: Systematic review and network meta-analysis.

BACKGROUND: Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's disease (PD). However, the optimal strategy, including the type and dose of COMT inhibitors remains unknown. This systematic review and network meta-analysis aimed to assess the efficacy and safety of different COMT inhibitors and for treating PD patients. METHODS: PubMed, Embase, Cochrane Library and Web of Science were screened up to November 20, 2022. Randomized controlled trials (RCTs) of COMT inhibitors (entacapone, opicapone, tolcapone) for PD patients were included. Eligible outcomes were total ON-time, rate of ON-time >1 h, total daily dose of levodopa therapy, mean change from baseline to final follow up in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, adverse events and dyskinesia. Network meta-analyses integrated direct and indirect evidence with placebo as a common comparator. RESULTS: We identified 18 studies with 7564 patients. Opicapone, entacapone, and tolcapone could increase total ON-time when compared with placebo. However, opicapone (25 mg, MD 4.0, 95%CrI: 1.1-7.5) and opicapone (50 mg, MD 5.1, 95%CrI: 2.2-8.7) statistically significant increase the total ON-time. opicapone and entacapone could increase the rate of ON-time >1 h when compared with placebo. Only opicapone (5 mg) showed no statistically significant with placebo (OR 1.4, 95%CrI: 0.74-2.4). We found that opicapone (50 mg, SURCA, 0.796) is the best option compared with other treatments. TOL (200 mg) was ranked highest in the rank probability test for total daily dose of levodopa therapy, followed by OPI (50 mg), TOL (400 mg) and TOL (100 mg) in order. SUCRA rankings identified TOL (200 mg) as the most likely therapy for increasing adverse events (SUCRA 27.19%), followed by TOL (400 mg, SUCRA 27.20%) and OPI (5 mg, SUCRA 30.81%). The SUCRA probabilities were 91.6%, 75.2%, 67.9%, 59.3%, 45.6%, 41.1%, 35.1%, 24.6% and 9.4% for PLA, TOL (400 mg), ENT (100 mg), ENT (200 mg), OPI (5 mg), TOL (100 mg), OPI (25 mg), OPI (50 mg), and TOL (200 mg) respectively. CONCLUSION: In conclusion, opicapone (50 mg) may be a better choice for treatment PD when compared with other COMT inhibitors.

Correction: Zhang et al. Dynamic Multi-Objective Optimization in Brazier-Type Gasification and Carbonization Furnace. Materials 2023, 16, 1164.

In consideration of the contributions to this work, Feng Qian unequivocally requests the removal of his name from the author list of this publication [...].

A universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification with multiple signal readout.

Rapid and sensitive detection of nucleic acids has become crucial in various fields. However, most current nucleic acid detection methods can only be used in specific scenarios, such as RT-qPCR, which relies on fluorometer for signal readout, limiting its application at home or in the field due to its high price. In this paper, a universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification (CRISPR-SDA) with multiple signal readout was established to adapt to different application scenarios. Nucleocapsid protein gene of SARS-CoV-2 (N gene) and hepatitis B virus (HBV) DNA were selected as model targets. The proposed strategy achieved the sensitivity of 53.1 fM, 0.15 pM, and 1 pM for N gene in fluorescence mode, personal glucose meter (PGM) mode and lateral flow assay (LFA) mode, respectively. It possessed the ability to differentiate single-base mismatch and the presence of salmon sperm DNA with a mass up to 105-fold of the targets did not significantly interfere with the assay signal. The general and modular design idea made CRISPR-SDA as simple as building blocks to construct nucleic acid sensing methods to meet different requirements by simply changing the SDA template and selecting suitable signal report probes, which was expected to find a breadth of applications in nucleic acids detection.

Influence of conditioner and straw on the herbaceous plant-based phytoremediation copper tailings: a field trial at Liujiagou tailings pond, China.

A field trial was performed to carry out an enhanced phytoremediation technique for multi-metal contaminated copper tailings by Sudan grass (Sorghum Sudanese), ryegrass (Lolium perenne L.), and Bermuda grass (Cynodon dactylon), using conditioner (TH-LZ01) and straw combination into composite amendments as soil amendments, aimed to obtain the maximum of phytoremediation effect. The results showed that compared with untreated herbaceous plants, the application of conditioner and straw planted with herbaceous plants reduced the pH and conductivity and increased the organic matter and water content of the copper tailings to different degrees. With the addition of conditioner and straw, the DTPA-Cd, DTPA-Cu, DTPA-Pb, and DTPA-Zn contents in the copper tailings showed a decreasing trend compared with the untreated group. The herbaceous plants were promoted to reduce the percentage contents of acid soluble fractions Cd, Cu, Pb, and Zn and to increase the percentage contents of reducible, oxidizable, and residual fractions heavy metals (Cd, Cu, Pb, and Zn) in the copper tailings to different degrees. The contents of Cd, Cu, Pb, and Zn in the underground part of herbaceous plants were higher than those in the aboveground part, and the contents of Cd, Cu, Pb, and Zn in the aboveground part and underground part decreased after adding conditioner and straw, which indicated that the conditioner and straw inhibited the transport of heavy metals in the plant. Furthermore, the principal component analysis showed that the application of conditioner and straw with planting ryegrass had more potential for improving the physicochemical properties of copper tailings and reducing heavy metal toxicity, followed by Bermuda grass and Sudan grass.

Roles of red mud in remediation of contaminated soil in mining areas: Mechanisms, advances and perspectives.

Red mud (RM) is a kind of strong alkaline solid waste produced from the aluminum industry, which contributes significantly to environmental pollution and can cause severe health issues.Currently, RM is widely recognized as a potential material for soil remediation because of its rich metal oxide content, such as Fe/Al oxides. However, there is no comprehensive description on the roles of RM in passivation remediation of contaminated soil in mining areas. This review summarizes the mechanisms of passivation of heavy metals (HMs) in contaminated soil by RM, including precipitation, adsorption and ion exchange. Besides the effects of adding RM on soil physicochemical properties, heavy metal forms and ecological environment are further elaborated. Moreover, using the co-hydrothermal carbonization of RM and biomass for enhancing the efficiency of contaminated soil remediation is proposed as the main prospective research. This paper provides technical references for the resource utilization of RM and the treatment of heavy metal-contaminated soil.

Preparation of thiol-free amino acid plasma matrix for quantification of thiol amino acids and their oxidized forms in human plasma by UPLC-MS/MS.

Thiol amino acids, with great physiological significance, are unstable, and have small molecular weights, as well as very low endogenous concentrations. Therefore, to quantitatively and directly analyze them using liquid chromatography-tandem mass spectrometry is difficult. To overcome these problems, we aimed to prepare a thiol-free amino acid plasm matrix as blank sample to reduce the background for the first time. Using compounds with maleimide group that react with classical thiols to generate water-insoluble products. Reducing agents Tris(2-carboxyethyl)phosphine (TCEP) was applied to cooperate with bismaleimide (DM) for elimination of thiol amino acids from plasma 10 min at room temperature and pH 7. Further, the residual TCEP from plasma were removed using an anion exchange resin within 10 min. Methodological validation analysis revealed good performance in linearity, precision, extraction recovery (≥ 82 %), and stability (except oxidized glutathione). This quantitative analysis was successfully applied to blood samples of 9 people in good health. This study provides a foundation for the development of accurate and rigorous quantitative analysis methods targeting thiol amino acids in different body fluids or tissues. Moreover, it paves the way toward realizing several clinical applications.

Endothelial cell serum and glucocorticoid regulated kinase 1 (SGK1) mediates vascular stiffening.

BACKGROUND: Excessive dietary salt intake increases vascular stiffness in humans, especially in salt-sensitive populations. While we recently suggested that the endothelial sodium channel (EnNaC) contributes to salt-sensitivity related endothelial cell (EC) and arterial stiffening, mechanistic understanding remains incomplete. This study therefore aimed to explore the role of EC-serum and glucocorticoid regulated kinase 1 (SGK1), as a reported regulator of sodium channels, in EC and arterial stiffening. METHODS AND RESULTS: A mouse model of salt sensitivity-associated vascular stiffening was produced by subcutaneous implantation of slow-release deoxycorticosterone acetate (DOCA) pellets, with salt (1 % NaCl, 0.2 % KCl) administered via drinking water. Preliminary data showed that global SGK1 deletion caused significantly decreased blood pressure (BP), EnNaC activity and aortic endothelium stiffness as compared to control mice following DOCA-salt treatment. To probe EC signaling pathways, selective deletion of EC-SGK1 was performed by cross-breeding cadherin 5-Cre mice with sgk1flox/flox mice. DOCA-salt treated control mice had significantly increased BP, EC and aortic stiffness in vivo and ex vivo, which were attenuated by EC-SGK1 deficiency. To demonstrate relevance to humans, human aortic ECs were cultured in the absence or presence of aldosterone and high salt with or without the SGK1 inhibitor, EMD638683 (10uM or 25uM). Treatment with aldosterone and high salt increased intrinsic stiffness of ECs, which was prevented by SGK1 inhibition. Further, the SGK1 inhibitor prevented aldosterone and high salt induced actin polymerization, a key mechanism in cellular stiffening. CONCLUSION: EC-SGK1 contributes to salt-sensitivity related EC and aortic stiffening by mechanisms appearing to involve regulation of actin polymerization.

Prevalence and clinical correlates of hyperhomocysteinemia in Chinese urban population with hypertension.

Context: The coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease. Objective: The aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension. Methods: A cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis. Results: The prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male (B = 1.430, OR = 4.179) and MTHFR (TT) (B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender (B = -2.784, P = 0.004), MTHFR genotypes (B = 1.410, P = 0.005), and FA levels (B = -0.136, P = 0.030). Conclusion: The high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices.

High Engraftment and Metastatic Rates in Orthotopic Xenograft Models of Gastric Cancer via Direct Implantation of Tumor Cell Suspensions.

Although the implantation of intact tumor fragments is a common practice to generate orthotopic xenografts to study tumor invasion and metastasis, the direct implantation of tumor cell suspensions is necessary when prior manipulations of tumor cells are required. However, the establishment of orthotopic xenografts using tumor cell suspensions is not mature, and a comparative study directly comparing their engraftment and metastatic capabilities is lacking. It is unclear whether tumor fragments are superior to cell suspensions for successful engraftment and metastasis. In this study, we employed three GC cell lines with varying metastatic capacities to stably express firefly luciferase for monitoring tumor progression in real time. We successfully minimized the risk of cell leakage during the orthotopic injection of tumor cell suspensions without Corning Matrigel by systematically optimizing the surgical procedure, injection volume, and needle size options. Comparable high engraftment and metastatic rates between these two methods were demonstrated using MKN-45 cells with a strong metastatic ability. Importantly, our approach can adjust the rate of tumor progression flexibly and cuts the experimental timeline from 10-12 weeks (for tumor fragments) to 4-5 weeks. Collectively, we provided a highly reproducible procedure with a shortened experimental timeline and low cost for establishing orthotopic GC xenografts via the direct implantation of tumor cell suspensions.