Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease.

BACKGROUND: Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. METHODS: This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0 ± 11.8 years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. RESULTS: Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 ± 0.16 vs. 1.08 ± 0.15, P = 0.028 for the right ABI; 1.01 ± 0.16 vs. 1.06 ± 0.16, P = 0.002 for the left ABI) and VRI (0.83 ± 0.57 vs. 1.08 ± 0.56, P < 0.001) and had higher serum levels of ICAM-1 (P < 0.001), VCAM-1 (P = 0.003) and ET-1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. CONCLUSIONS: Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.

Health-literacy, self-efficacy and health-outcomes of patients undergoing haemodialysis: Mediating role of self-management.

BACKGROUND: Health literacy, self-efficacy and self-management are known to influence health-related well-being. However, the precise influence of self-management, health literacy and self-efficacy on health outcomes in Asian countries is under-researched. OBJECTIVES: To examine the impact of health literacy and self-efficacy (independent variables) and self-management (mediator) on patients' health outcomes (dependent variable). DESIGN: An observational, cross-sectional design was conducted between 1 March 2022 and 31 August 2022. PARTICIPANTS: Outpatients receiving haemodialysis (n = 200) at a Taiwanese medical centre were assessed. MEASUREMENTS: The survey included demographic questions and standardised scales: the 3-item Brief Health Literacy Screen, the 8-item Perceived Kidney/Dialysis Self-Management Scale as a measure of self-efficacy, and the 20-item Haemodialyses Self-Management Instrument. Health outcomes were responses on the 12-item Short-Form Health Survey version 2 and clinical blood results from the past 3 months. RESULTS: Participants aged over 60 exhibited common comorbidities, with 34% showing low health literacy. Biochemical markers (e.g., haemoglobin and albumin) significantly correlated with physical and mental health scores. Mediating coefficients revealed that self-management significantly influenced associations between health outcomes, health literacy (ß = 0.31; p < 0.01), and self-efficacy (ß = 0.19; p < 0.01). IMPLICATIONS FOR PRACTICE: Self-management can modify the overall influence of health literacy and self-efficacy on patients' quality of physical and emotional health. When managing a chronic condition, 'knowing' how to self-manage does not always result in 'doing so' by the patient. Continuous monitoring and promoting self-management behaviours and support by nurses are crucial to enhance health outcomes.

Novel equations incorporating the sarcopenia index based on serum creatinine and cystatin C to predict appendicular skeletal muscle mass in patients with nondialysis CKD.

BACKGROUND & AIMS: Skeletal muscle mass measurements are important for customizing nutritional strategies for patients with chronic kidney disease (CKD). The serum creatinine-to-cystatin C ratio (Cr/CysC) is a potential indicator of sarcopenia. We developed simple equations to predict the appendicular skeletal muscle mass (ASM) of patients with CKD using readily available parameters and Cr/CysC. METHODS: Overall, 573 patients with nondialysis CKD stages 3-5 were included for developing and validating the equations. The participants were randomly divided into development and validation groups in a 2:1 ratio. ASM was measured using the Body Composition Monitor (BCM), a multifrequency bioelectrical impedance spectroscopy device. The height, weight, anthropometric data, and handgrip strength (HGS) of the participants were obtained. Equations were generated using stepwise multiple linear regression models. The prognostic significance of the predicted ASM was evaluated in a CKD registry comprising 1043 patients. RESULTS: The optimal equation without anthropometric data and HGS (Equation 1) was as follows: ASM (kg) = -7.949 - 0.049 × Age (years) - 2.213 × Woman + 0.090 × Height (cm) + 0.210 × Weight (kg) + 1.141 × Cr/CysC. The modified equation (Equation 2) with anthropometric data and HGS was as follows: ASM (kg) = -4.468 - 0.050 × Age (years) - 2.285 × Woman+ 0.079 × Height (cm) + 0.228 × Weight (kg) - 0.127 × Mid-arm muscular circumference (cm) + 1.127 × Cr/CysC. Both equations exhibited strong correlations with the ASM measured via BCM in the validation cohort (r = 0.944 and 0.943 for Equations 1 and 2, respectively) with minimal bias. When Equation 1 was applied to the CKD registry, the estimated ASM index (ASM/Height2) significantly predicted overall mortality over a median of 54 months. CONCLUSIONS: Novel ASM equations offer a simple method for predicting skeletal muscle mass and can provide valuable prognostic information regarding patients with nondialysis CKD.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (ß: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; ß: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Buoyancy of underground structures and pore water pressure conduction law in silty clay strata.

Based on the effective stress principle, indoor model tests were conducted in this study to calculate the buoyancy of an underground structure and determine the law of pore water pressure conduction in silty clay strata. A comprehensive underground structure-water-soil interaction test system was established with four-in-one features: Elimination of lateral friction, controllable water head, circulating water supply and drainage, and simulation of groundwater flow. Four- and seven-gradient buoyancy continuous monitoring tests were completed using fine sand and silty clay, respectively, to verify the reliability and accuracy of the test system. The hydrostatic pressure and seepage-hydrostatic process of the silty clay strata were simulated separately to investigate the buoyancy of the underground structure of the strata, the buoyancy reduction coefficient, and the pore water pressure conduction law. The results show the reliability and accuracy of the comprehensive test system for underground structure-water-soil interaction. The concept of "buoyancy starting intercept" is proposed based on this system, where the underground water level value should be the head of water supply minus the "buoyancy starting intercept" when calculating buoyancy in weak permeable layers. Under hydrostatic action, the groundwater is phreatic, deeper burial depths show greater magnitude of this discount. When the groundwater is confined, the water head reduction coefficient increases with increase in the burial depth or hydraulic gradient. Buoyancy calculations of an underground structure within the range of confined water should not be reduced in this case. Whether in a seepage or hydrostatic state, the pore water pressure in the silty clay layer is below the theoretical value. The results of this work may provide a theoretical basis for further analysis of the pore water pressure conduction law and buoyancy reduction mechanism of clay soils. We also may provide a theoretical reference for the development of innovative underground structure-water-soil interaction comprehensive test systems.

Licochalcone A regulates viral IRES activity to inhibit enterovirus replication.

Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host autophagy pathway to facilitate the completion of their life cycle. Therefore, we selected an autophagy compound library to screen for autophagy-related compounds that may affect viral growth. By using the neutralization screening assay, we identified a compound, 'licochalcone A' that significantly inhibited EV-D68 replication. To investigate the mechanism by which licochalcone A inhibits EV-D68 replication and to identify the viral life cycle stage it inhibits, the time-of-addition, viral attachment, viral entry, and dual-luciferase reporter assays were performed. The results of the time-of-addition assay showed that licochalcone A, a characteristic chalcone found in liquorice roots and widely used in traditional Chinese medicine, inhibits EV-D68 replication during the early stages of the viral life cycle, while those of the dual-luciferase reporter assay showed that licochalcone A does not regulate viral attachment and entry, but inhibits EV-D68 IRES-dependent translation. Licochalcone A also inhibited enterovirus A71 and coxsackievirus B3 but did not significantly inhibit dengue virus 2 or human coronavirus 229E replication. Licochalcone A regulates IRES translation to inhibit EV-D68 viral replication.

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus.

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (ß = 0.52, 95% confidence interval [CI] = 0.01-1.03, p = 0.046), high HOMA-IR (ß = 0.60, 95% CI = 0.12-1.08, p = 0.015), and a high PD glucose load (ß = 0.58, 95% CI = 0.08-1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

A novel mucosal bivalent vaccine of EV-A71/EV-D68 adjuvanted with polysaccharides from Ganoderma lucidum protects mice against EV-A71 and EV-D68 lethal challenge.

BACKGROUND: Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections. METHODS: In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant. RESULTS: The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them. CONCLUSIONS: These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections.

An overview of commercialization and marketization of thermoelectric generators for low-temperature waste heat recovery.

According to statistics, low-temperature waste heat below 300°C accounts for more than 89% of industrial waste heat. If the waste heat is not recycled, a large amount of low-temperature waste heat will be released into the atmosphere, thereby exacerbating global warming and posing a significant threat to human survival. Although the power generation efficiency of solid-state thermoelectric generation technology is lower than the organic Rankine cycle, it only requires a smaller construction area, which increases its market acceptance, applicability, and penetration. Especially in the pursuit of net-zero emissions by global companies, the importance of low-temperature waste heat recovery and power generation is even more prominent. The current thermoelectric conversion efficiency of commercial thermoelectric chips is about 5%. Power generation cost, thermoelectric conversion efficiency, and energy use efficiency are highly correlated with the commercialization of solid-state thermoelectric technology. This research shares five practical waste heat power generation cases commercialized by recycling three heat sources. It also points out the three significant challenges facing the commercialization of power generation from low-temperature waste heat recovery. This study analyzes 2,365 TEG patents submitted by 28 companies worldwide to determine the basic technology for realizing waste heat recovery through TEG and explore the potential commercialization of related waste heat recovery products. The future challenge for the large-scale commercialization of solid-state thermoelectric technology is not technological development but financial incentives related to changes in international energy prices and subsidies that promote zero carbon emissions.

Enhanced Yield of Bioactive Compounds and Antioxidant Activities in Four Fermented Beans of Phellinus linteus Strains (Agaricomycetes) by Solid-State Fermentation.

Phellinus linteus is a famous medicinal mushroom which exhibits various biological activities. This study aimed to investigate the effects of solid-state fermentation by Ph. linteus on the yield of bioactive compounds and antioxidant activities of beans. Four bean substrates were prepared and inoculated with inoculum of three strains of Ph. linteus, respectively. During the cultivation, the harvested samples were dried, grounded, extracted, and determined the contents of bioactive compounds and antioxidant activities. The results indicated that the mung bean fermented by Ph. linteus 04 had the highest polysaccharide content (98.8 mg/g). The highest total phenolic and flavonoid contents were in fermented soybeans by Ph. linteus 03 (15.03 mg gallic acid equivalents/g and 63.24 mg rutin equivalents/g, respectively). The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities of hot water extracts were higher than those of ethanolic extracts for fermented beans by three Ph. linteus strains. However, the superoxide anion radical scavenging ability of ethanolic extracts was higher than those of hot water extracts in the fermented beans of the three strains. The ferrous ion (Fe2+)-chelating abilities of hot water extracts were higher than those of ethanolic extracts in fermented beans by Ph. linteus 03 and 04. In contrast, ethanolic extracts were higher than hot water extracts in fermented beans by Ph. linteus 06. Overall, these results indicate that the fermentation by Ph. linteus strains increased the bioactive compounds and antioxidant activities of four beans.

Resistin: A Potential Indicator of Aortic Stiffness in Non-Dialysis Chronic Kidney Disease Patients.

Background and Objectives: In the progression and development of atherosclerosis, resistin plays a significant role. Chronic kidney disease (CKD), frequently associated with atherosclerosis, exhibits a marked increase in morbidity and mortality rates. This study set out to explore the association between aortic stiffness and serum levels of resistin in non-dialysis-dependent CKD patients ranging from stages 3 to 5. Materials and Methods: We collected fasting blood samples from 240 CKD patients across stages 3 to 5. The concentration of resistin in serum was determined using a commercially available enzyme immunoassay kit. Those patients who exhibited a carotid-femoral pulse wave velocity (cfPWV) greater than 10 m/s were identified as the aortic stiffness group. Results: Out of the 240 CKD patients, 88 (36.7%) were classified within the aortic stiffness group. This group demonstrated higher incidences of diabetes, advanced age, increased body weight, body mass index, body fat mass, systolic and diastolic blood pressure, fasting glucose, and serum resistin levels. Multivariate logistic regression analysis highlighted resistin, diabetes, and body weight as independent predictors of aortic stiffness. Additionally, body fat mass, logarithmically transformed cfPWV (log-cfPWV) values and log-triglyceride levels were independent predictors of log-resistin levels by multivariate stepwise linear regression analysis. Conclusions: In CKD patients from stages 3 to 5, a positive correlation exists between elevated serum resistin levels and cfPWV values, identifying resistin as a potential predictor of aortic stiffness.

The Association between Serum Adiponectin Levels and Endothelial Function in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

Adiponectin is the richest human circulating adipokine with anti-inflammatory, antioxidant, and insulin-sensitizing effects. We evaluated the association between serum adiponectin levels and endothelial function in chronic kidney disease (CKD) patients, obtaining fasting blood samples from 130 non-dialysis CKD subjects. We measured the endothelial function-represented by the vascular reactivity index (VRI)-via non-invasive digital thermal monitoring, and serum adiponectin concentrations by enzyme immunoassay kits. A total of 22 (16.9%), 39 (30.0%), and 69 (53.1%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. Elevated serum blood urea nitrogen (BUN) level was negatively correlated with VRI values, but serum adiponectin and estimated glomerular filtration rate were positively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly positive association of adiponectin (p < 0.001), and the significantly negative association of log-BUN (p = 0.021) with VRI values in CKD subjects remained. In an animal study using in vitro blood-vessel myography, treatment with adiponectin enhancing acetylcholine-mediated vasorelaxation in 5/6 nephrectomy CKD mice. Our study results indicated that adiponectin concentration was positively associated with VRI values and modulated endothelial function in non-dialysis CKD patients.

Effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region.

The effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region was assessed using a GDS dynamic triaxial test system. The strength parameters, dynamic elastic modulus, damping ratio, and other dynamic parameters of the soil samples were analyzed under different temperature conditions. The results demonstrated that the shear strength parameters (internal friction angle and cohesion) of the silty clay under a dynamic load increased significantly with decreasing temperature, and the internal friction angle increased sharply below 0 °C. The dynamic elastic modulus increased as the temperature decreased and changed significantly in the ice-water phase change region. The slope of the dynamic stress-strain curve of the soil sample increased significantly with decreasing temperature. As the temperature decreased, the damping ratio reduced, and the ability of the soil to absorb seismic waves declines. The research results provide new data and information to guide construction projects in seasonally frozen region.

Positive Association of Serum Galectin-3 with the Development of Aortic Stiffness of Patients on Peritoneal Dialysis.

A novel cardiovascular stress biomarker known as galectin-3 might be useful for anticipating adverse cardiovascular outcomes. The objective of the current investigation was to assess the association between serum galectin-3 levels and aortic stiffness (AS) in 196 patients on peritoneal dialysis. An enzyme-linked immunosorbent examination and a cuff-based volumetric displacement were employed to determine the levels of serum galectin-3 and the carotid-femoral pulse wave velocity (cfPWV), respectively. The AS group had 48 patients in total (24.5%) with cfPWV greater than 10 m/s. The AS group, when compared with the group without AS, had a significantly higher prevalence of diabetes mellitus and hypertension in addition to greater fasting glucose levels, waist circumference, systolic blood pressure, and serum galectin-3 levels. Multivariate logistic and linear regression analysis demonstrated that serum glactin-3 levels, in addition to gender and age, were significantly and independently associated with cfPWV and AS. Serum galectin-3 levels were linked with AS, according to a receiver operating characteristic curve analysis, with an area under the curve of 0.648 (95% confidence interval, 0.576-0.714; p = 0.0018). In summary, there was a significant correlation between serum galectin-3 levels and cfPWV in patients undergoing peritoneal dialysis therapy for end-stage kidney disease.

Experimental study on soil-water characteristics and strength characteristics of complete-intense weathering mudstone in seasonal frozen area.

To study the soil-water characteristics and shear strength of unsaturated complete-intense weathering mudstone, the soil-water characteristic curve of complete-intense weathering mudstone and the matric suction of mudstone samples under natural state were measured. This measurement was through a soil-water characteristic test using a pressure plate instrument. Based on the results of soil-water characteristic test, an unsaturated (saturated) triaxial shear test was carried out. Under different temperatures and confining pressure conditions, the shear strength and deformation characteristics of complete-intense weathering mudstone under natural water content and saturation conditions were investigated. The results show that the percentage of silt and clay in unsaturated complete-intense weathering mudstone in natural state is relatively high, with the mudstone having less sand, and a weak permeability and exhibiting a significant capillary phenomenon. The complete-intense weathering mudstone with a natural moisture content of 19.15% has a matric suction of 210 kPa. When the temperature is constant, the shear stress of the sample increases with the increase of confining pressure. When the temperature decreases from 0 to -20°C, the influence of confining pressure on the rock samples gradually decreases. The rock sample has the property of strain hardening during shearing. Under the same matric suction, the total cohesion increases with the decrease of temperature. At a positive temperature, the effective internal friction angle increases with the decrease of temperature. At a negative temperature, the lower the temperature, the smaller the effective internal friction angle. The test of shear strength parameters of saturated complete-intense weathering mudstone is simple and conservative. In practical engineering, the basic properties of unsaturated complete-intense weathering mudstone can be predicted by testing the shear strength parameters of saturated complete-intense weathering mudstone. The results of the study are important for better understanding the nature of unsaturated complete-intense weathering mudstone and improving the safety of engineering construction in complete-intense weathering mudstone areas.

M2-like macrophages polarized by Foxp3- Treg-of-B cells ameliorate imiquimod-induced psoriasis.

Our group have demonstrated that splenic B cells contributed to the CD4+ CD25- naive T cells conversion into CD4+ CD25+ Foxp3- regulatory T cells without adding appended cytokines, named Treg-of-B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg-of-B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co-cultured the bone marrow-derived macrophages (BMDMs) with Treg-of-B cells under LPS/IFN-γ stimulation and analyzed the M2-associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg-of-B cell-induced M2 macrophage for skin inflammation using imiquimod (IMQ)-induced psoriatic mouse model. Our results showed that BMDMs co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, including Arg-1, IL-10, Pdcd1lg2, MGL-1, IL-4, YM1/2 and CD206. In an inflammatory environment, TNF-α and IL-6 production by macrophages co-cultured with Treg-of-B cells was decreased significantly. The molecular mechanism revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact-dependent manner. Moreover, the treatment with Treg-of-B cell-induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ-induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg-of-B cell-induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3- Treg-of-B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell-based therapeutic strategy for psoriasis.

Vitamin K and vascular calcification in chronic kidney disease: An update of current evidence.

Vascular calcification, characterized by calcium deposition in the intimal and medial layers of the arterial wall, is frequently encountered in patients with chronic kidney disease (CKD) and leads to an enhanced risk of adverse cardiovascular (CV) outcomes. However, the underlying complex pathophysiology remains incompletely understood. Recently, Vitamin K supplementation aimed at correcting Vitamin K deficiency highly prevalent in CKD holds great promise to mitigate the progression of vascular calcification. This article discusses the functional Vitamin K status in CKD, the pathophysiology linking Vitamin K deficiency and vascular calcification, and reviews current literature from animal models, observational studies, and clinical trials across the different spectrum of CKD. While favorable effects of Vitamin K on vascular calcification and CV outcomes are suggested in animal and observational studies, most recently published clinical trials investigating the effects of Vitamin K on vascular health failed to support the beneficial role of Vitamin K supplementation, despite improving the functional status of Vitamin K. We address the potential reasons for these discrepancies and provide further perspective on Vitamin K research in CKD.

Cisplatin and Albumin-Based Gold-Cisplatin Nanoparticles Enhance Ablative Radiation Therapy-Induced Antitumor Immunity in Local and Distant Tumor Microenvironment.

PURPOSE: Ablative radiation therapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity. METHODS AND MATERIALS: The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au-cisplatin NPs. RESULTS: Combining ablative RT with cisplatin or Au-cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells, including natural killer T cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au-cisplatin NPs group. Cisplatin and Au-cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed unirradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector tumor-infiltrating immune cells including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au-cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect. CONCLUSIONS: Compared with cisplatin, the albumin-based Au-cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events and can be safely administered concurrently with ablative RT. Alternative NP formulations may be designed to further improve anticancer outcomes.