Development and characterization of Zn-xCu-yTi-zMo alloys for biomedical applications: a high-throughput gradient continuous casting approach.

The limited mechanical properties of pure Zn, such as its low strength and ductility, hinder its application as a material for biodegradable implants. Addressing this challenge, the current study focuses on the development of biodegradable Zn-based alloys, employing innovative alloy design and processing strategies. Here, alloys with compositions ranging from 0.02 to 0.10 weight percent (wt.%) Cu, 1.22 to 1.80 wt.% Ti, and 0.04 to 0.06 wt.% Mo were produced utilizing a high-throughput gradient continuous casting process. This study highlights three specific alloys: Zn-1.82Cu-0.10Ti-0.05Mo (HR8), Zn-0.08Cu-1.86Ti-0Mo (HR7), and Zn-1.26Cu-0.13Ti-0.06Mo (HR6), which were extensively evaluated for their microstructure, mechanical properties, electrochemical performance, potential as bioimplants, and cytotoxicity. These alloys were found to exhibit enhanced mechanical strength, optimal degradation rates, and superior biocompatibility, evidenced by in-vivo experiments with SD rats, positioning them as promising candidates for medical implants. This research not only introduces a significant advancement in biodegradable alloy development but also proposes an efficient method for their production, marking a pivotal step forward in biomedical engineering. STATEMENT OF SIGNIFICANCE: The limited mechanical properties of pure Zn have hindered its application in biodegradable implants. Our research primarily focuses on the alloy design and process strategies of biodegradable Zn-based alloys. We explore the Zn-Cux-Tix-Mox alloys. This study introduces a high-throughput experimental approach for efficient screening of multi-component alloy systems with optimal properties. The Zn-Cux-Tix-Mox alloys were designed and processed through gradient continuous casting, followed by homogenization and hot rolling. Our findings indicate that the Zn-1.82Cu-0.10Ti-0.05Mo alloy demonstrates superior tensile, mechanical, and corrosion properties post hot rolling. The study suggests that Zn-0.13Cu-1.26Ti-0.06Mo, Zn-0.08Cu-1.86Ti-0Mo, and Zn-1.82Cu-0.10Ti-0.05Mo alloys hold significant potential as biodegradable materials.

Bone marrow macrophages are involved in the ineffective hematopoiesis of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age-paired patients with lower-risk MDS (N = 15), higher-risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro-inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher-risk MDS compared to lower-risk MDS. BM MФs from patients with higher-risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower-risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower-risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher-risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower-risk MDS. Gene Ontology enrichment comparing BM MΦs from lower-risk MDS and higher-risk MDS for genes was involved in hematopoiesis- and immunity-related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS.

Efficacy and Safety of Yanggan Jian in Hepatitis B Virus-related Decompensated Cirrhosis: A Randomized, Double-blind, Controlled Trial.

Background and Aims: The aim was to evaluate the efficacy and safety of Yanggan Jian (YGJ) in HBV-infected patients with decompensated cirrhosis. Methods: This randomized, double-blind controlled trial enrolled 160 patients with HBV-related decompensated cirrhosis who were already receiving or about to start antiviral therapy. Patients were randomly assigned to receive YGJ or placebo for 24 weeks, and were followed-up to 36 weeks. The primary outcome was the proportion of patients with a ≥2 point reduction in Child-Turcotte-Pugh (CTP) score from baseline at week 24. Secondary outcomes were CTP class and score, serum liver function indices, mortality, incidence of hepatocellular carcinoma and variceal bleeding. Results: The proportion of patients with a CTP score reduction ≥2 was significantly greater in the YGJ than in the placebo group (p=0.009); the percentage of patients with CTP class C was significantly less than that in the placebo group (p<0.05), and the YGJ group had a significantly greater mean change from baseline in CTP score at week 24 (p=0.034). The improvement in measured values and change from baseline of prothrombin time, serum albumin, platelets, cholinesterase, international normalized ratio, and activated partial thromboplastin time were significantly better with YGJ than with placebo. Between-group differences in cumulative rates of variceal bleeding, hepatocellular carcinoma, death, or the frequency of any adverse event (AE), AEs related to treatment, or discontinuation because of AEs were not significant. Conclusions: YGJ significantly improved CTP scores and hepatic synthetic and reserve function in patients with HBV-related decompensated cirrhosis, and was safe and well tolerated.

Improved function and balance in T cell modulation by endothelial cells in young people.

Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cell frequencies, but the underlying mechanism is still unclear. Endothelial cells (ECs), which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and elderly healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy. Although the young and elderly EC percentages were comparable, young ECs showed fewer reactive oxygen species and better migratory and tube-forming abilities than elderly ECs. Notably, increased T cell activation molecules and inflammatory cytokines were found in elderly ECs which regulated T cells to differentiate into more proinflammatory T cells, including Th1 and Tc1 cells, than young ECs.

Monocyte subsets in bone marrow grafts may contribute to a low incidence of acute graft-vs-host disease for young donors.

Young donors are associated with a lower cumulative incidence of acute graft-vs-host disease (aGVHD) after allogenic haematopoietic stem cell transplantation (allo-HSCT) than old donors. Although grafts are harvested from healthy donors, it is unclear whether donor age is associated with aGVHD occurrence owing to its effect on cell compositions in grafts. Moreover, the differences in monocyte subsets in grafts between young and old donors and the association between monocyte subsets in bone marrow (BM) grafts and aGVHD remain to be elucidated. In the current study, non-classical monocytes and the CD4+ /CD8+ T cell ratio were remarkably decreased in BM grafts in donors <30 years old. Multivariate analysis further revealed that the level of non-classical monocytes in BM grafts (≥0.31 × 106 /kg) was an independent risk factor for the occurrence of II-IV aGVHD. In summary, our data indicate that non-classical monocytes in BM grafts may help identify patients at high risk for aGVHD after allo-HSCT. Although further validation is required, our results suggest that the low level of non-classical monocytes and a low ratio of CD4+ /CD8+ T cell in BM grafts may be correlated with the lower incidence of aGVHD in young donors.

Association of Triglyceride to high-density lipoprotein cholesterol ratio and incident of diabetes mellitus: a secondary retrospective analysis based on a Chinese cohort study.

BACKGROUND: Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) is one of major risk factors of insulin resistance and diabetes. However, study on the association between TG/HDL-C and diabetes mellitus (DM) risk is limited, especially in Chinese people. This study was undertaken to investigate the relationship between TG/HDL-C and incident of diabetes in a large cohort in Chinese population. METHODS: The present study was a retrospective cohort study. A total of 114,787 adults from Rich Healthcare Group in China, which includes all medical records for participants who received a health check from 2010 to 2016. The target independent variable and the dependent variable were triglyceride to high-density lipoprotein cholesterol ratio measured at baseline and incident of diabetes mellitus appeared during follow-up respectively. Covariates involved in this study included age, gender, body mass index, diastolic blood pressure, systolic blood pressure, fasting plasma glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes. Cox proportional-hazards regression was used to investigate the association of TG/HDL-C and diabetes. Generalized additive models was used to identify non-linear relationships. Additionally, we also performed a subgroup analysis. It was stated that the data had been uploaded to the DATADRYAD website. RESULT: After adjusting age, gender, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes, result showed TG/HDL-C was positively associated with incident of diabetes mellitus (HR = 1.159, 95%CI (1.104, 1.215)). A non-linear relationship was detected between TG/HDL-C and incident of diabetes, which had an inflection point of TG/HDL-C was 1.186. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.718(1.433,2.060) and 1.049(0.981,1.120), respectively. Subgroup analysis showed, the stronger association can be found in the population with fasting plasma glucose (FPG) < 6.1 mmol/L (P for interaction< 0.0001; HR = 1.296 with FPG < 6.1 mmol/L vs HR = 1.051 with FPG ≥ 6.1 mmol/L).The same trend was also seen in the population with body mass index (BMI)(≥18.5, < 24 kg/m2) (P for interaction = 0.010,HR = 1.324) and family history without diabetes(P for interaction = 0.025, HR = 1.170). CONCLUSION: TG/HDL-C is positively associated with diabetes risk. The relationship between TG/HDL-C and incident of diabetes is also non-linear. TG/HDL-C was strong positively related to incident of diabetes when TG/HDL-C is less than 1.186.

Classification of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern in Patients with Hepatitis B Cirrhosis Using Metabonomics.

OBJECTIVE: This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques. METHODS: The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography-time-of-flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. RESULTS: After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns. CONCLUSIONS: The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.

An integrated course based on two dimensional-electrophoresis and mass spectrometry analysis to teach proteomic techniques for undergraduate students.

Here, we developed an integrated course based on two dimensional-electrophoresis and spectrometry mass (2DE-MS) technique for undergraduate students to help them learn proteomic techniques. The soluble proteins in wild type and gene knockout bacteria were separated by 2DE and the differently expressed proteins were identified by MS analysis. The proteomic data was finally confirmed by RT-PCR detection. The separated experiments of 2DE, MS, RNA isolation, RT-PCR, as well as essential bioinformatic analysis, were integrated into a one-week course, which provided students an opportunity to systematically understand the proteomic techniques and their applications in current scientific research. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:354-360, 2018.

[Correlation between fasting C-peptide and serum uric acid in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between fasting C-peptide (F-CP) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 347 hospitalized patients with T2DM were stratified according to F-CP level to analyze the impact of increased F-CP levels on SUA level and the incidence of hyperuricemia (HUA). The patients with an elevated SUA level (>420 µmol/L) and a normal SUA level (≤420 µmol/L) were compared for general data, fasting C-peptide and other clinical indexes. Pearson or Spearman correlation analysis was used to analyze the correlation of SUA level with F-CP levels and other parameters. The risk factors of elevated SUA were analyzed by binary logistic regression, multiple regression analysis and hierarchical interaction analysis. The ROC curve was used to analyze the independent risk factors of elevated SUA and determine the corresponding cut-off values. RESULTS: Compared with those with a normal SUA level, patients with elevated SUA had higher body mass index (BMI), waist-to-hip ratio, F-CP, postprandial 2hC peptide (2hP-CP), triglyceride (TG), homocysteine (HCY), serum creatinine (SCr) level (P<0.05), and a greater percentage of drinking (44.8% vs 32.6%, P=0.006), but had significantly lowered levels of HbA1c, high-density lipoprotein (HDL), and estimated glomerular filtration rate (eGFR) (P<0.05). SUA was found to be positively correlated with F-CP, 2hP-CP, BMI, waist-to-hip ratio, diastolic blood pressure, TG, HCY, SCr, smoking and drinking (P<0.05), and was negatively correlated with gender, age, age of disease onset, HbA1c, HDL and eGFR (P<0.05). SUA level and the incidence of hyperuricemia increasea significantly with F-CP level (P<0.05). F-CP was identified as an independent risk factor for elevated SUA, and gender did not affect the relationship between F-CP and SUA. ROC curve analysis showed that a F-CP level >1.260 ng/mL was associated with a significantly increased risk of hyperuricemia in T2DM patients. CONCLUSION: F-CP is closely related with SUA and may be an independent risk factor of elevated SUA in patients with T2DM.