Investigating the effect of history of fractures and hypertension on the risk of all-cause death from osteoporosis: A retrospective cohort study.

To assess the coexistence effect between history of fractures and hypertension on the all-cause death risk of osteoporosis. In this retrospective cohort study, some characteristics of osteoporosis patients aged ≥ 20 years were extracted from the National Health and Nutrition Examination Survey (NHANES) database (2005-2010, 2013-2014), such as age, gender, smoking, drinking, the history of diabetes, cardiovascular and cerebrovascular diseases, fractures and hypertension. The outcome of this study was defined as all-cause death of osteoporosis. These patients were followed up until 2015 with an average follow-up time of 62.00 ± 34.79 months. Univariate and multivariate logistic regression was utilized to evaluate the association of history of fractures and hypertension on all-cause death risk of osteoporosis, respectively. The death risk factors were presented by using relative risk (RR) and 95% confidence interval (CI). The attributable proportion (AP) to explore the interaction between history of fractures and hypertension on the all-cause death risk of osteoporosis. Of the total 801 osteoporosis patients, 227 died. After adjusting age, gender, marital status, education background, annual household income, diabetes, the prior use of prednisone or cortisone medication, cardiovascular and cerebrovascular diseases, the history of fractures (RR = 1.502, 95% CI: 1.035-2.180), spine fracture (RR = 2.944, 95% CI: 1.244-6.967), hip fracture (RR = 2.033, 95% CI: 1.066-3.875) was significantly associated with the increased death risk of osteoporosis. However, there was no significant difference between hypertension and the all-cause death risk of osteoporosis (P > .05). Additionally, there was a significant interaction between the history of fractures and hypertension on the all-cause death risk of osteoporosis, and the interaction was an enhancement effect (AP = 0.456, 95% CI: 0.005-0.906). The co-existence of the history of fractures and hypertension could increase the all-cause death risk of osteoporosis, which indicated that osteoporosis patients with the history of fractures should actively monitor blood pressure levels and prevent the occurrence of hypertension.

Suprachoroidal injection of polyzwitterion hydrogel for treating glaucoma.

Glaucoma is the primary cause of irreversible blindness worldwide. The current treatments are primarily based on drug usage or surgical operation to reduce intraocular pressure (IOP). However, it is expensive and requires patients to insist on taking the medicine for a long time. The suprachoroidal space (SCS) is the space between the choroid and the sclera, which forms part of the uveovortex pathway in the circulation of aqueous humor. So far, it is still challenging to realize the injection of hydrogels into the SCS with long-term duration. In this work, an in situ-forming polyzwitterionic polycarboxybetaine hydrogel is designed and injected to expand SCS to increase the drainage of aqueous humor from the eye via the uveovortex pathway, thus reducing IOP for at least 6 weeks, while commercial hyaluronic acid hydrogel can only last for about 4 weeks. The clinical ophthalmological safety assessment examination shows that the treatment of polyzwitterion hydrogel is well-tolerated that leads to minimal inflammatory reaction, and histopathology assessment demonstrates that the SCS is expanded after injection of the hydrogel. Further analysis of ultrasound biomicroscopy reveals that there is a strong correlation between IOP reduction and SCS expansion. In short, the polyzwitterion hydrogel developed in this work can prolong the period of IOP reduction by expanding SCS, thus treating ocular hypertension and glaucoma without resorting to drugs or regular surgery.

Magnetic Evaluation of Heat-Resistant Martensitic Steel Subjected to Microstructure Degradation.

The present paper investigates the use of the magnetic hysteresis loop technique to nondestructively evaluate microstructural degradation in heat-resistant martensitic (HRM) steels. The degradation impairs the safe operation of thermal power plants and it is thus essential to periodically assess it using nondestructive evaluation (NDE) techniques. In this contribution, HRM steels are thermally aged up to 16,000 h at 675 °C to simulate the microstructural degradation, then the changes in the magnetic coercivity, hardness, and microstructure are systematically characterized and the relations between them are determined. Both coercivity and hardness decrease with thermal aging duration, which can be interpreted in terms of the microstructure parameters' evolution based on the pinning of crystal defects on domain walls and dislocations. Coercivity and hardness share the same softening trend with aging time, and good linear relations between coercivity, hardness, and microstructure parameters are found. These results provide a key to understanding the magnetic parameter evolution in HRM steels and suggest the possibility of using magnetic technologies for the NDE of microstructure degradation in thermal power plants.

On the Formability of Medium Mn Steel Treated with Varied Thermal Processing Routes.

In this contribution, we investigate the influence of thermal processing routes on the formability of medium Mn steel by assessing the strain hardening coefficient and anisotropy factor using the uniaxial tensile test. Medium Mn steel processed by intercritical annealing (IA) at 680 °C for 4 h demonstrates better formability than steel treated with a combination of IA at 800 °C for 10 min and quenching and partitioning (Q&P), based on the much higher strain hardening coefficient (n) and comparable anisotropy factor (r, rm, ∆r). The higher strain hardening coefficient of medium Mn steel with single IA treatment is ascribed to the enhanced transformation-induced plasticity (TRIP) effect resulting from the large amount of austenite that is transformed into martensite during deformation. In addition, the IA process allows for the production of medium Mn steel with high ductility, which is beneficial for its high formability and good 'part ductility' in lightweight automotive applications.

Preparation of pH-indicator films based on soy protein isolate/bromothymol blue and methyl red for monitoring fresh-cut apple freshness.

Intelligent pH-indicator films based on soy protein isolate (SPI) were prepared using pH-sensitive dyes (bromothymol blue and methyl red). The addition of mixed indicators imparts pH-indicator films with an appreciable microstructure, acceptable water resistance, and favorable optical properties. The incorporation of the mixed indicators did not lead to significant improvement in the mechanical properties of films due to weak ionic cross-linking by hydrogen bonding between the SPI macromolecules and low-molecular-weight indicators. Fourier-transform infrared spectroscopy indicated hydrogen bond-mediated intermolecular interactions, and scanning electron microscopy showed that BB/MR were well dispersed in the SPI film. The indicator addition hindered the sorption and passage of water molecules. The water vapor permeability, moisture sorption, moisture content, and total soluble matter were 4.32 to 6.12 ×10-12  g·cm/cm2 ·s·Pa, 36.70% to 73.33%, 25.28% to 44.11%, and 8.21% to 25.56%, respectively. Also, the addition of indicators reduced UV light transmittance with minimal effect on the transparency of the film. The presence of indicators enhanced the pH sensitivity, seen as a visible color reaction at different pHs (total color difference, ΔE > 5). When the pH-indicator film containing 8 ml/100 ml final film emulsions was used to monitor the fresh-cut apple freshness, a green color for fresh status was observed, which turned blue after 60 h. Collectively, our findings suggested that indicator-containing SPI films have the potential for monitoring the freshness of fruits. PRACTICAL APPLICATION: pH-indicator films can help consumers to identify the freshness of packaged food by a change in the color of the packaging material, which is easily visible to the unaided eye without the need for opening the packaging. This protects consumers' interests.

The structural mechanism for the nucleoside tri- and diphosphate hydrolysis activity of Ntdp from Staphylococcus aureus.

Staphylococcus aureus is a well-known clinical pathogenic bacterium. In recent years, due to the emergence of multiple drug-resistant strains of S. aureus in clinical practice, S. aureus infections have become an increasingly severe clinical problem. Ntdp (nucleoside tri- and diphosphatase, also known as Sa1684) is a nucleotide phosphatase that has a significant effect on the proliferation of S. aureus colonies and the killing ability of the host. Here, we identified the nucleoside tri- and diphosphate hydrolysis activity of Ntdp and obtained the three-dimensional structures of apo-Ntdp and three substrate analog (ATPγ S, GDPß S, and GTPγ S) complexes of Ntdp. Through structural analysis and biochemical verification, we illustrated the structural basis for the divalent cation selectivity, substrate recognition model, and catalytic mechanism of Ntdp. We also revealed a possible basal functional pattern of the DUF402 domain and hypothesized the potential pathways by which the protein regulates the expression of the two-component regulatory factor agr and the downstream virulence factors. Overall, the above findings provide crucial insights into our understanding of the Ntdp functional mechanism in the infection process.

Continuous spectrum of glucose dysmetabolism due to the KCNJ11 gene mutation-Case reports and review of the literature.

The KCNJ11 gene encodes the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium (KATP ) channel, which plays a key role in insulin secretion. Monogenic diseases caused by KCNJ11 gene mutation are rare and easily misdiagnosed. It has been shown that mutations in the KCNJ11 gene are associated with neonatal diabetes mellitus (NDM), maturity-onset diabetes of the young 13 (MODY13), type 2 diabetes mellitus (T2DM), and hyperinsulinemic hypoglycemia. We report four patients with KCNJ11 gene mutations and provide a systematic review of the literature. A boy with diabetes onset at the age of 1 month was misdiagnosed as type 1 diabetes mellitus (T1DM) for 12 years and received insulin therapy continuously, resulting in poor glycemic control. He was diagnosed as NDM with KCNJ11 E322K gene mutation, and glibenclamide was given to replace exogenous insulin. The successful transfer time was 4 months, much longer than the previous unsuccessful standard of 4 weeks. The other three patients were two sisters and their mother; the younger sister was misdiagnosed with T1DM at 13 years old, while the elder sister was diagnosed with diabetes (type undefined) at 16 years old. They were treated with insulin for 3 years, with poor glycemic control. Their mother was diagnosed with T2DM and achieved good glycemia control with glimepiride. They were diagnosed as MODY13 because of the autosomal dominant inheritance of two generations, early onset of diabetes before 25 years of age in the two sisters, and the presence of the KCNJ11 N48D gene mutation. All patients successfully transferred to sulfonylureas with excellent glycemic control. Therefore, the wide spectrum of clinical phenotypes of glucose dysmetabolism caused by KCNJ11 should be recognized to reduce misdiagnosis and implement appropriate treatment.

Neutrophil count as a reliable marker for diabetic kidney disease in autoimmune diabetes.

BACKGROUND: A growing body of evidence supports neutrophils as having an active role in the development of diabetic kidney disease (DKD). However, the clinical relevance of neutrophils and DKD in autoimmune diabetes remains unknown. This study aimed to investigate the relationship between circulating neutrophils and DKD in autoimmune diabetes. METHODS: Patients with type 1 diabetes (T1D, n = 226) and latent autoimmune diabetes in adults (LADA, n = 79) were enrolled and stratified according to the urinary albumin to creatinine ratio (ACR). Circulating levels of white blood cells (WBCs), including neutrophils, were measured in a central laboratory, and the neutrophil-to-lymphocyte ratio (NLR) was calculated. The risk factors associated with DKD were analysed by logistic regression. RESULTS: In T1D and LADA patients, the peripheral neutrophil counts increased in parallel with DKD advancement. The neutrophil counts in the patients with macroalbuminuria were significantly higher than those in the patients with normoalbuminuria for each type of diabetes. Furthermore, neutrophil counts positively correlated with ACR in T1D. In addition, neutrophils were independently associated with DKD in T1D in the logistic regression analysis, when various well-known risk factors, including age, gender, disease duration, hypertension, dyslipidemia and smoking status, were adjusted. CONCLUSIONS: Neutrophil counts are closely associated with DKD in patients with autoimmune diabetes, suggesting that neutrophil-mediated inflammation may be involved in the pathogenesis of DKD in patients with autoimmune diabetes.

Genetic diversity and fingerprinting of 33 standard flue-cured tobacco varieties for use in distinctness, uniformity, and stability testing.

BACKGROUND: At present, the distinctness, uniformity, and stability (DUS) testing of flue-cured tobacco (Nicotiana tabacum L.) depends on field morphological identification, which is problematic in that it is labor intensive, time-consuming, and susceptible to environmental impacts. In order to improve the efficiency and accuracy of tobacco DUS testing, the development of a molecular marker-based method for genetic diversity identification is urgently needed. RESULTS: In total, 91 simple sequence repeats (SSR) markers with clear and polymorphic amplification bands were obtained with polymorphism information content, Nei index, and Shannon information index values of 0.3603, 0.4040, and 0.7228, respectively. Clustering analysis showed that the 33 study varieties, which are standard varieties for flue-cured tobacco DUS testing, could all be distinguished from one another. Further analysis showed that a minimum of 25 markers were required to identify the genetic diversity of these varieties. Following the principle of two markers per linkage group, 48 pairs of SSR markers were selected. Correlation analysis showed that the genetic relationships revealed by the 48 SSR markers were consistent with those found using the 91 SSR markers. CONCLUSIONS: The genetic fingerprints of the 33 standard varieties of flue-cured tobacco were constructed using 48 SSR markers, and an SSR marker-based identification technique for new tobacco varieties was developed. This study provides a reliable technological approach for determining the novelty of new tobacco varieties and offers a solid technical basis for the accreditation and protection of new tobacco varieties.

Tanshinone IIA inhibits osteosarcoma growth through modulation of AMPK-Nrf2 signaling pathway.

Tanshinone IIA (Tan IIA) is a member of the major lipophilic components extracted from the root of Salvia miltiorrhiza Bunge. Osteosarcomas are primary malignant tumors of bone. The aim of our study is to explore the role of Tan IIA in osteosarcomas survival, migration, and proliferation. MG63 osteosarcoma cell line was cultured in vitro and treated with different concentrations of Tan IIA. Then, ELISA, immunofluorescence, qPCR, western blots, and pathway analysis were conducted to verify whether Tan II modulated osteosarcoma survival, migration, and proliferation through the AMPK/Nrf2 signaling pathway. Our results indicated that Tan IIA dose-dependently inhibited MG63 osteosarcoma cell survival, migration, and proliferation. Mechanistically, Tan IIA reduced cell viability and inhibited the transcriptions of migratory factors. In addition, the number of proliferative MG63 osteosarcoma cell was also reduced by Tan IIA. Molecular investigations demonstrated that Tan IIA treatment caused a drop in the transcriptions and activities of AMPK and Nrf2. Interestingly, knockdown of AMPK and Nrf2 markedly attenuated MG63 osteosarcoma cell survival, migration, and proliferation. Altogether, our results indicate that Tan IIA could be used as an effective anticancer drug to control osteosarcoma proliferation through affecting its survival, migration, and proliferation.

Molecular architecture of the DNA-binding sites of the P-loop ATPases MipZ and ParA from Caulobacter crescentus.

The spatiotemporal regulation of chromosome segregation and cell division in Caulobacter crescentus is mediated by two different P-loop ATPases, ParA and MipZ. Both of these proteins form dynamic concentration gradients that control the positioning of regulatory targets within the cell. Their proper localization depends on their nucleotide-dependent cycling between a monomeric and a dimeric state and on the ability of the dimeric species to associate with the nucleoid. In this study, we use a combination of genetic screening, biochemical analysis and hydrogen/deuterium exchange mass spectrometry to comprehensively map the residues mediating the interactions of MipZ and ParA with DNA. We show that MipZ has non-specific DNA-binding activity that relies on an array of positively charged and hydrophobic residues lining both sides of the dimer interface. Extending our analysis to ParA, we find that the MipZ and ParA DNA-binding sites differ markedly in composition, although their relative positions on the dimer surface and their mode of DNA binding are conserved. In line with previous experimental work, bioinformatic analysis suggests that the same principles may apply to other members of the P-loop ATPase family. P-loop ATPases thus share common mechanistic features, although their functions have diverged considerably during the course of evolution.

Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet ß-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual ß-cells, reverse ß-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet ß-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM.

[Poly-aspartamide-glutamic acid grafted low molecular weight polyethylenimine as a novel non-viral gene vector].

OBJECTIVE: To develop a novel gene delivery vector with poly-aspartamide-glutamic acid and polyethylenimine as the backbone. METHODS: alpha, beta-poly-(N-2-hydroxypropyl)-D, L-aspartamide-glutamic acid (PHPAG) was synthesized and low molecular weight polyethylenimine (PEI 1.8 kDa) was grafted to form PHPAG-PEI 1800. Chemical and biological characterization of the polymer was identified. RESULT: The polymer was confirmed by (1)H-NMR, and the molecular weight was about 1.2 x 10(4). The ability of DNA binding was showed by gel retardation assay at N/P ratio of 3. 5. MTT assay showed that the polymer was non toxic in COS-7 and A293 cell lines. In vitro test demonstrated that it had high transfection efficiency in B16 and Hela cell lines. CONCLUSION: PHPAG-PEI 1800 was successfully synthesized,which might be a potential vector for gene delivery.