Despite years of research investigating osteoblast differentiation, the mechanisms by which transcription factors regulate osteoblast maturation, bone formation, and bone homeostasis is still ...unclear. It has been reported that runt-related transcription factor 1 (Runx1) is expressed in osteoblast progenitors, pre-osteoblasts, and mature osteoblasts; yet, surprisingly, the exact function of RUNX1 in osteoblast maturation and bone formation remains unknown. Here, we generated and characterized a pre-osteoblast and differentiating chondrocyte-specific Runx1 conditional knockout mouse model to study RUNX1's function in bone formation. Runx1 ablation in osteoblast precursors and differentiating chondrocytes via osterix-Cre (Osx-Cre) resulted in an osteoporotic phenotype and decreased bone density in the long bones and skulls of Runx1f/fOsx-Cre mice compared with Runx1f/f and Osx-Cre mice. RUNX1 deficiency reduced the expression of SRY-box transcription factor 9 (SOX9), Indian hedgehog signaling molecule (IHH), Patched (PTC), and cyclin D1 in the growth plate, and also reduced the expression of osteocalcin (OCN), OSX, activating transcription factor 4 (ATF4), and RUNX2 in osteoblasts. ChIP assays and promoter activity mapping revealed that RUNX1 directly associates with the Runx2 gene promoter and up-regulates Runx2 expression. Furthermore, the ChIP data also showed that RUNX1 associates with the Ocn promoter. In conclusion, RUNX1 up-regulates the expression of Runx2 and multiple bone-specific genes, and plays an indispensable role in bone formation and homeostasis in both trabecular and cortical bone. We propose that stimulating Runx1 activity may be useful in therapeutic approaches for managing some bone diseases such as osteoporosis.
A hepatocellular carcinoma targeting lactoferrin (Lf) modified PEGylated liposome system was developed for improving drug efficacies to hepatic cancer cells. In this present work, PEGylated liposomes ...(PLS) were successfully prepared by the thin film hydration method combined with peglipid post insertion. Lf was covalently conjugated to the distal end of DSPE-PEG2000-COOH lipid by amide bound and loaded onto PEGylated liposomes surface as the targeting ligand. To confirm the targeting efficacies to hepatic cancer, coumarin-6 and DiR were encapsulated as fluorescent probes. The confocal microscopy and flow cytometry demonstrated that Lf conjugated PEGylated liposomes (Lf–PLS) were efficiently associated by HepG2 cells, while limited interaction was found for liposomes modified with a negative control protein. A similar pharmacokinetic behavior was observed in pharmacokinetics study of the liposomal formulations. Meanwhile, the in vivo imaging of liposomes in HepG2 tumor bearing mice indicated that Lf–PLS achieved more accumulation in tumor compared with PLS without Lf conjugated. The significant in vitro and in vivo results suggested that Lf–PLS might be a promising drug delivery system for hepatocellular carcinoma therapy with low toxicity.
Background Insulin resistance (IR) is a pivotal pathogenic component of metabolic diseases. It is crucial to identify convenient and reliable indicators of insulin resistance for its early detection. ...This study aimed at assessing the predictive ability of seven novel obesity and lipid-related indices. Methods A total of 5,847 female and 3,532 male healthy subjects were included in the study. The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), lipid accumulation products (LAP), body roundness index (BRI), body adiposity index (BAI), and visceral adiposity index (VAI) were measured and calculated using the established formulae. IR was diagnosed using the homeostatic model assessment of insulin resistance (HOMA-IR) index over the third quantile. Results The levels of all seven lipid-related indices were significantly higher in subjects with higher HOMA-IR values than in those with lower HOMA-IR values. These indices displayed moderate to high effectiveness receiver operating characteristic (ROC) curve-area under the curve (AUC) > 0.6 in predicting IR. Among them, TyG-BMI (AUC: 0.729), LAP (AUC: 0.708), and TyG-WC (AUC: 0.698) showed the strongest association with HOMA-IR. In the female population, the AUC for TyG-BMI, LAP, and TyG-WC in predicting IR was 0.732, 0.705, and 0.718, respectively. Logistic regression analysis showed the optimal cut-off values of those indicators in predicting IR as follows: TyG-BMI: male subjects – 115.16 odds ratio (OR) = 6.05, 95% CI: 5.09–7.19, female subjects – 101.58 (OR = 4.55, 95% CI: 4.00–5.16); LAP: male subjects – 25.99 (OR = 4.53, 95% CI: 3.82–5.38), female subjects – 16.11 (OR = 3.65, 95% CI: 3.22–4.14); and TyG-WC: male subjects – 409.43 (OR = 5.23, 95% CI: 4.48–6.24), female subjects – 342.48 (OR = 4.07, 95% CI: 3.59–4.61). Conclusion TyG-index-related parameters and LAP appear to be effective predictors of IR in the Chinese population. Specifically, TyG-BMI may be the most appropriate predictor of IR.
The Global Leader Initiative on Malnutrition (GLIM) criteria have been recommended for malnutrition diagnosis recently, for which the first step is malnutrition risk screening with any validated ...tool. This study aims to investigate the incidence of nutritional risk and malnutrition in Crohn's disease inpatients and compare the suitability of Nutritional Risk Screening 2002 (NRS-2002) and Malnutrition Universal Screening Tool (MUST) as the first-step screening tool for GLIM criteria.
We retrospectively analyzed the clinical data of Crohn's disease inpatients in our hospital from August 2016 to December 2019. NRS-2002 and MUST were used for nutritional screening at the time of admission. GLIM and Patient Generated-Subjective Global Assessment (PG-SGA) were used for malnutrition assessment, respectively. Patients without nutritional risk screened by NRS-2002 but with malnutrition risk screened by MUST were especially screened out. The appendicular skeletal muscle mass index (ASMI), fat-free mass index (FFMI), body fat percent (BFP), and body cell mass (BCM) were measured by the Biospace Inbody S10 composition analyzer.
A total of 146 Crohn's disease patients were enrolled, of which 62.3 and 89.7% had nutritional or malnutrition risk according to NRS-2002 and MUST, respectively. The prevalence of malnutrition assessed by GLIM was 59.6% (87 cases) and 82.2% (120 cases) when NRS-2002 and MUST were used as the first step of GLIM respectively. Meanwhile, 99 patients (67.8%) had malnutrition when assessed by PG-SGA. There were 41 patients who were not at nutritional risk according to NRS-2002 but were at malnutrition risk determined by MUST. At last, 33 patients were GLIM-defined, and 16 patients were PG-SGA-defined malnutrition among the 41 patients.
The nutritional risk or malnutrition is common in Crohn's disease inpatients. It is recommended to use a variety of nutritional assessment tools for Crohn's disease inpatients. MUST can be used as a good supplement for the patients with a score of NRS-2002 lower than 3 in order to decrease the miss rate of GLIM-defined malnutrition.
The muscle-related indicator is removed from Global Leadership Initiative on Malnutrition (GLIM) criteria implemented in China for many reasons. Patients with hematopoietic stem cell transplants are ...at nutrition risk and can enter into the second step of GLIM; thus, they are suitable for learning the diagnosing malnutrition significance between primary GLIM and GLIM-China criteria. This article aims to explore the role of muscle mass in the diagnostic criteria of malnutrition and the effects of GLIM-China for diagnosing malnutrition.
A total of 98 inpatients with hematopoietic stem cell transplants (HSCT) were recruited. Nutrition risk was assessed by using the Nutritional Risk Screening 2002 (NRS-2002). Appendicular skeletal muscle mass (ASMI) and fat-free mass index (FFMI) were determined using the bioelectrical impedance analysis (BIA) method. Malnutrition is defined by GLIM-China, GLIM, and PG-SGA. We use erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation in GLIM and GLIM-China. The correlation or consistency among ASMI, FFMI, ESR, CRP, GLIM-China, GLIM, and PG-SGA was evaluated, respectively.
One hundred percent instead of the patients had nutritional risk. The magnitude of malnutrition using PG-SGA, GLIM, and GLIM-China was 75.5, 80.6, and 64.3%, respectively. GLIM-China and PG-SGA showed the same performance (
= 0.052 vs. 1.00) and agreement (kappa = 0.404 vs. 0.433,
< 0.0001) with the FFMI. Consistency was noted between ASMI and PG-SGA in the assessment of malnutrition (
= 0.664) with a good agreement (kappa = 0.562,
= 0.084). ASMI and FFMI could determine muscle mass reduction, which could not be determined by BMI, albumin (ALB), and pre-albumin (pre-ALB); 34% of GLIM-China (-) patients were with low ASMI, and 40% with low FFMI; 30.0% of patients with PG-SGA (<4) still have low ASMI, and 38.2% have low FFMI.
If only the PG-SGA scale is used as a diagnostic criterion for evaluating malnutrition, a large proportion of patients with reduced muscle mass will be missed, but more patients with muscle loss will be missed
GLIM-China. Muscle-related indicators will help diagnose malnutrition.
The widespread use of antibiotics has caused the rapid emergence of antibiotic‐resistant bacterial strains and antibiotic resistance genes in the past few decades. Photocatalytic inactivation, a ...promising approach for the killing of pathogens, efficiently avoids the problems induced by antimicrobial drugs. However, traditional photocatalysts usually have some disadvantages, such as high costs of raw materials, ultraviolet ray excitation, and potential leaching of toxic metals. Here, a metal‐free heterojunction photocatalyst, denoted as CQDs/g‐C3N4, is synthesized through incorporating carbon quantum dots (CQDs) on graphitic carbon nitride (g‐C3N4), which significantly enhances photocatalytic inactivation of Staphylococcus aureus (S. aureus) compared with pure g‐C3N4 in vitro. CQDs/g‐C3N4 causes a rapid increase of intracellular reactive oxygen species levels and destruction of cell membranes under visible light, eventually leading to death of bacteria. The efficacy of CQDs/g‐C3N4 is further examined by a mouse cutaneous infection model of S. aureus. CQDs/g‐C3N4 markedly reduces the bacterial loads and prompts lesion recovery in mice, as compared with g‐C3N4‐treated group. In vivo and in vitro toxicity analyses show that the side effects of CQDs/g‐C3N4 are negligible. Considering the efficient photocatalytic inactivation and nontoxicity of CQDs/g‐C3N4, this visible‐light‐driven photocatalyst paves a brand new avenue for the treatment of S. aureus infection.
A nontoxic photocatalyst denoted as carbon quantum dots/graphitic carbon nitride (CQDs/g‐C3N4) is constructed, which significantly enhances photocatalytic inactivation of Staphylococcus aureus as compared with pure g‐C3N4 both in vitro and in vivo. CQDs/g‐C3N4, the visible‐light‐driven photocatalyst, markedly reduces the bacterial loads and prompts lesion recovery, paving a brand new avenue for the treatment of S. aureus infection.
We aimed to assess whether blood glucose control can be used as predictors for the severity of 2019 coronavirus disease (COVID‐19) and to improve the management of diabetic patients with COVID‐19. A ...two‐center cohort with a total of 241 confirmed cases of COVID‐19 with definite outcomes was studied. After the diagnosis of COVID‐19, the clinical data and laboratory results were collected, the fasting blood glucose levels were followed up at initial, middle stage of admission and discharge, the severity of the COVID‐19 was assessed at any time from admission to discharge. Hyperglycemia patients with COVID‐19 were divided into three groups: good blood glucose control, fair blood glucose control, and blood glucose deterioration. The relationship of blood glucose levels, blood glucose control status, and severe COVID‐19 were analyzed by univariate and multivariable regression analysis. In our cohort, 21.16% were severe cases and 78.84% were nonsevere cases. Admission hyperglycemia (adjusted odds ratio aOR, 1.938; 95% confidence interval 95% CI, 1.387–2.707), mid‐term hyperglycemia (aOR, 1.758; 95% CI, 1.325–2.332), and blood glucose deterioration (aOR, 22.783; 95% CI, 2.661–195.071) were identified as the risk factors of severe COVID‐19. Receiver operating characteristic (ROC) curve analysis, reaching an area under ROC curve of 0.806, and a sensitivity and specificity of 80.40% and 68.40%, respectively, revealed that hyperglycemia on admission and blood glucose deterioration of diabetic patients are potential predictive factors for severe COVID‐19. Our results indicated that admission hyperglycemia and blood glucose deterioration were positively correlated with the risk factor for severe COVID‐19, and deterioration of blood glucose may be more likely to the occurrence of severe illness in COVID‐19.
Highlights
High fasting blood glucose level, especially the initial level at admission was an important risk factor for severe cases.
Deterioration of blood glucose may be more likely to the occurrence of severe 2019 coronavirus disease.
This study reports a high-performance 3D stainless-steel photoanode (3D SS photoanode) for bioelectrochemical systems (BESs). The 3D SS photoanode consists of 3D carbon-coated SS felt bioactive side ...and a flat α-Fe2O3-coated SS plate photoactive side. Without light illumination, the electrode reached a current density of 26.2 ± 1.9 A m−2, which was already one of the highest current densities reported thus far. Under illumination, the current density of the electrode was further increased to 46.5 ± 2.9 A m−2. The mechanism of the photo-enhanced current production can be attributed to the reduced charge-transfer resistance between electrode surface and the biofilm with illumination. It was also found that long-term light illumination can enhance the biofilm formation on the 3D SS photoanode. These findings demonstrate that using the synergistic effect of photocatalysis and microbial electrocatalysis is an efficient way to boost the current production of the existing high-performance 3D anodes for BESs.
Display omitted
•High current density (26.2 A m−2) was achieved on carbon-coating SS felt.•Photocatalyst could further increase the current of carbon-SS felt to 46.5 A m−2.•Electron transfer between electrode/biofilm was accelerated by instant illumination.•Biofilm morphology was optimized in the pressure of long-term illumination.
The widespread use of antibiotics has caused the rapid emergence of antibiotic-resistant bacterial strains and antibiotic resistance genes in the past few decades. Photocatalytic inactivation, a ...promising approach for the killing of pathogens, efficiently avoids the problems induced by antimicrobial drugs. However, traditional photocatalysts usually have some disadvantages, such as high costs of raw materials, ultraviolet ray excitation, and potential leaching of toxic metals. Here, a metal-free heterojunction photocatalyst, denoted as CQDs/g-C
N
, is synthesized through incorporating carbon quantum dots (CQDs) on graphitic carbon nitride (g-C
N
), which significantly enhances photocatalytic inactivation of Staphylococcus aureus (S. aureus) compared with pure g-C
N
in vitro. CQDs/g-C
N
causes a rapid increase of intracellular reactive oxygen species levels and destruction of cell membranes under visible light, eventually leading to death of bacteria. The efficacy of CQDs/g-C
N
is further examined by a mouse cutaneous infection model of S. aureus. CQDs/g-C
N
markedly reduces the bacterial loads and prompts lesion recovery in mice, as compared with g-C
N
-treated group. In vivo and in vitro toxicity analyses show that the side effects of CQDs/g-C
N
are negligible. Considering the efficient photocatalytic inactivation and nontoxicity of CQDs/g-C
N
, this visible-light-driven photocatalyst paves a brand new avenue for the treatment of S. aureus infection.
PDF
