A static magnetic field improves bone quality and balances the function of bone cells with regulation on iron metabolism and redox status in type 1 diabetes.

Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.

Cirsiliol induces autophagy and mitochondrial apoptosis through the AKT/FOXO1 axis and influences methotrexate resistance in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown. METHODS: The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS. RESULTS: Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo. CONCLUSIONS: Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.

Deep learning parametric response mapping from inspiratory chest CT scans: a new approach for small airway disease screening.

OBJECTIVES: Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. METHODS: We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. RESULTS: Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001). CONCLUSION: Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry.

Improving the efficiency of identifying malignant pulmonary nodules before surgery via a combination of artificial intelligence CT image recognition and serum autoantibodies.

OBJECTIVE: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure. METHODS: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set. RESULTS: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022). CONCLUSIONS: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters. KEY POINTS: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement.

Prognostic impact of deep learning-based quantification in clinical stage 0-I lung adenocarcinoma.

OBJECTIVES: To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. METHODS: A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. RESULTS: The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. CONCLUSION: DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. CLINICAL RELEVANCE STATEMENT: Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. KEY POINTS: • Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). • For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. • The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.

Age-dependent gender differences in the diagnosis and treatment of osteoporosis during hospitalization in patients with fragility fractures.

BACKGROUND: There is a gender difference in the acceptance of osteoporosis diagnosis and treatment in patients after fragility fractures, but this difference is rarely assessed during hospitalization, and it is unclear whether these differences are age-dependent. This study aimed to evaluate the differences between male and female fragility fracture patients of different age groups who received the diagnosis and treatment of osteoporosis during hospitalization. METHODS: 31,265 fragility fracture patients aged ≥ 50 years from the Fragility Fracture Management Database in a high-volume orthopedic hospital from December 2019 to February 2023 were included in this study. We compared the differences in the rates of men and women with fragility fracture who received the measurement of bone mineral density (BMD) and bone metabolism biochemical markers (BMBMs) and treatment with anti-osteoporosis medications (AOMs), and follow-up to the internal medicine clinic within 3 months after discharge, across all age groups and across different age stages (50-59, 60-69, 70-79, and ≥ 80 years). RESULTS: The detection rates of female patients receiving BMD and BMBMs during hospitalization were 31.88% and 5.30%, respectively, compared with 22.23% and 2.69% for men. The rate of receiving any AOMs treatment was 44.63% for women and 31.60% for men. The follow-up rate of returning to the internal medicine clinic within 3 months after discharge was 9.79% for women compared to 3.00% for men. There was a significant difference between males compared to females (P < 0.0001). Analysis of patients by different age group revealed that differences in the diagnosis and treatment of osteoporosis were found only in patients under 80 years of age, while gender differences in the return to the internal medicine clinic for follow-up after discharge were present in all age groups. CONCLUSIONS: Gender differences present in osteoporosis management in patients with fragility fracture during hospitalization, especially for patients under 80 years of age. This finding suggests that orthopedic surgeons neglect to manage osteoporosis in male patients with fragility fracture during hospitalization.

Photosynthetic response mechanism to polybrominated diphenyl ether exposure in Chlorella pyrenoidosa.

Polybrominated diphenyl ether (PBDE) contamination is common in aquatic environments and can severely damage aquatic organisms. However, there is a lack of information on the response and self-adaptation mechanisms of these organisms. Chlorella pyrenoidosa was treated with 2,2',4,4'-tetrabromodiphenyl ether (BDE47), causing significant growth inhibition, pigment reduction, oxidative stress, and chloroplast atrophy. Photosynthetic damage contributed to inhibition, as indicated by Fv/Fm, Chl a fluorescence induction, photosynthetic oxygen evolution activity, and photosystem subunit stoichiometry. Here, Chl a fluorescence induction and quinone electron acceptor (QA-) reoxidation kinetics showed that the PSII donor and acceptor sides were insensitive to BDE47. Quantitative analyses of D1 and PsaD proteins illustrated that PSII and PSI complexes were the main primary targets of photosynthesis inhibition by BDE47. Significant modulation of PSII complex might have been caused by the potential binding of BDE47 on D1 protein, and molecular docking was performed to investigate this. Increased activation of antioxidant defense systems and photosystem repair as a function of exposure time indicated a positive resistance to BDE47. After a 5-day exposure, 23 % of BDE47 was metabolized. Our findings suggest that C. pyrenoidosa has potential as a bioremediator for wastewater-borne PBDEs and can improve our understanding of ecological risks to microalgae.

Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.

Iron is one of the essential mineral elements for the human body and this nutrient deficiency is a worldwide public health problem. Iron is essential in oxygen transport, participates in many enzyme systems in the body, and is an important trace element in maintaining basic cellular life activities. Iron also plays an important role in collagen synthesis and vitamin D metabolism. Therefore, decrease in intracellular iron can lead to disturbance in the activity and function of osteoblasts and osteoclasts, resulting in imbalance in bone homeostasis and ultimately bone loss. Indeed, iron deficiency, with or without anemia, leads to osteopenia or osteoporosis, which has been revealed by numerous clinical observations and animal studies. This review presents current knowledge on iron metabolism under iron deficiency states and the diagnosis and prevention of iron deficiency and iron deficiency anemia (IDA). With emphasis, studies related to iron deficiency and bone loss are discussed, and the potential mechanisms of iron deficiency leading to bone loss are analyzed. Finally, several measures to promote complete recovery and prevention of iron deficiency are listed to improve quality of life, including bone health.

Taurine Protects against the Fatty Liver Hemorrhagic Syndrome in Laying Hens through the Regulation of Mitochondrial Homeostasis.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease caused by fat deposition in the liver of humans and mammals, while fatty liver hemorrhagic syndrome (FLHS) is a fatty liver disease in laying hens which can increase the mortality and cause severe economic losses to the laying industry. Increasing evidence has shown a close relationship between the occurrence of fatty liver disease and the disruption of mitochondrial homeostasis. Studies have proven that taurine can regulate hepatic fat metabolism, reduce hepatic fatty deposition, inhibit oxidative stress, and alleviate mitochondrial dysfunction. However, the mechanisms by which taurine regulates mitochondrial homeostasis in hepatocytes need to be further studied. In this study, we determined the effects and mechanisms of taurine on high-energy low-protein diet-induced FLHS in laying hens and in cultured hepatocytes in free fatty acid (FFA)-induced steatosis. The liver function, lipid metabolism, antioxidant capacity, mitochondrial function, mitochondrial dynamics, autophagy, and biosynthesis were detected. The results showed impaired liver structure and function, mitochondrial damage and dysfunction, lipid accumulation, and imbalance between mitochondrial fusion and fission, mitochondrial autophagy, and biosynthesis in both FLHS hens and steatosis hepatocytes. Taurine administration can significantly inhibit the occurrence of FLHS, protect mitochondria in hepatocytes from disease induced by lipid accumulation and FFA, up-regulate the expression levels of Mfn1, Mfn2, Opa1, LC3I, LC3II, PINK1, PGC-1α, Nrf1, Nrf2, and Tfam, and down-regulate the expression levels of Fis1, Drp1, and p62. In conclusion, taurine can protect laying hens from FLHS through the regulation of mitochondrial homeostasis, including the regulation of mitochondrial dynamics, autophagy, and biosynthesis.

Theoretical Study of NO Adsorption by Hydroxyl-Containing Char with the Participation of Na/K.

The study of the effects of Na and K on the heterogeneous adsorption of hydroxyl-containing char with NO is important for the clean utilization of high alkali coal. In this paper, the effects of Na/K atoms on the adsorption of NO on the char surface were investigated at the GGA-PBE level by choosing zigzag type, armchair type, and saturated hydroxyl-containing char structures based on DFT. It was found that the adsorption stability of NO on structures with active sites was greater for sites close to the hydroxyl group than that for sites far from the hydroxyl group. The stability of char doped by Na/K is related to the char structure and the position of functional groups. The most stable Na/K doped structures are Z-OH-2 (Eads= -350.50 kJ/mol) and A-OH-1-2 (Eads= -339.17 kJ/mol), respectively. The participation of Na/K can increase the adsorption energy of the three structures with NO, and especially the adsorption energy of saturated char with NO is increased by as much as 5 times. The reason for that is the promotion of the hybridization of the C and NO p orbitals. The comprehensive analysis of electrostatic potential, charge transfer, and front orbitals indicates that the effects of decorated sodium and potassium atoms on the char surface are very similar. This study lays a theoretical foundation for the study of the heterogeneous reduction process.

DFT Study on the Effect of Na on NO Reduction with Nitrogen-Containing Char from Zhundong Coal.

The effect mechanism of Na on reduction of NO with nitrogen-containing char, char(N) still lacks an in-depth study. Based on density functional theory, this study systematically discussed the heterogeneous reaction of NO with four char(N) models, that is, zigzag(N), zigzag(N)@Na, armchair(N), and armchair(N)@Na. Results show that the presence of Na promoted the chemisorption of NO on both zigzag(N) and armchair(N), especially zigzag(N). Mayer bond order analysis revealed that during NO reduction, Na catalyzed the breaking of N-O and C-N bonds in both models as well as dissociation of the N-N structure from the zigzag(N). Dynamics in the 300-1000 K range revealed that the rate constant for the decisive step increased in the order of zigzag(N) < zigzag(N)@Na < armchair(N) < armchair(N)@Na, while the activation energy presented a reverse order. The addition of Na promoted the electron transfer between NO and char(N) and exhibited an obvious catalytic effect on the NO-char(N) reaction by reducing activation energy and increasing the reaction rate constant for the decisive step.

Taurine Prevents AFB1-Induced Renal Injury by Inhibiting Oxidative Stress and Apoptosis.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins, which can cause serious kidney damage after ingestion. Taurine protects the kidney, an effect related to its antioxidation and anti-apoptotic actions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine on AFB1-induced renal injury in rats. The results show that taurine ameliorated the increase in serum blood urea nitrogen (BUN), blood creatinine (CRE), blood uric acid (UA), cystatin c (Cys-c), and urinary protein and AKP levels. Taurine also inhibits the content of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), succinate dehydrogenase (SDH), and the mRNA expression of SOD, nicotinamide adenine dinucleotide phosphate-quinine oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and glutamate cysteine ligase catalytic (GCLC) in rat kidney tissue. The apoptotic rate of renal cells was decreased by taurine through inhibition of a mitochondrial mechanism. In summary, we found that taurine prevents AFB1-induced renal injury via enhanced antioxidant ability and mitochondrial-dependent apoptosis.

Taurine Prevents Liver Injury by Reducing Oxidative Stress and Cytochrome C-Mediated Apoptosis in Broilers Under Low Temperature.

Hypoxia caused by low ambient temperature leads to hypoxemia in broilers, which aggravates the metabolic burden of the liver. Liver damage is closely related to oxidative stress and apoptosis. It has been proved that taurine can reduce oxygen free radicals, exert antioxidant properties, and inhibit mitochondria-dependent apoptosis. This experiment aimed to determine whether taurine could prevent liver damage by inhibiting oxidative stress and the cytochrome c-mediated apoptotic pathway in broilers under low ambient temperature. Broilers were given 1% taurine in drinking water, and the temperature was raised at 10 °C ~ 12 °C from 21 to 42 days. At 28 and 42 days, the hepatic tissues were collected. The antioxidant capacity of liver tissues and mRNA expression levels of the factors related with cytochrome c-medicated apoptosis pathway were measured. The results showed taurine significantly increased the total antioxidant capacity (T-AOC) at 28 days. Furthermore, taurine also increased the activities of glutathione peroxidase (GSH-PX) while reducing malondialdehyde (MDA) concentration at 28 days and 42 days. Our results also revealed that taurine significantly increased the mRNA expression levels of Hsp 27 and Hsp 90 while decreasing caspase-3 mRNA expression in broiler hepatocytes at 28 days. In addition, taurine also upregulated the expression level of Bcl-2 at 42 days. In summary, the present study found that taurine enhances the antioxidant ability and alleviates cytochrome c-mediated apoptosis in hepatic tissue of broilers under low temperature.

The Regulatory Effects of Taurine on Neurogenesis and Apoptosis of Neural Stem Cells in the Hippocampus of Rats.

The promotion of neurogenesis from neural stem cells (NSCs) in the hippocampus was found to be the most fundamental and effective therapy for depression. Our previous studies proved an antidepressive effect of taurine on rats, but the exact mechanism remains unclear. In this study, CUMS model was established in rats, and NSCs were cultured in vitro to investigate the protective effect and mechanisms of taurine on neurogenesis and apoptosis in CUMS rats and glutamate-injured NSCs. The results showed that ki67-positive cells were significantly increased by taurine, while apoptosis in the DG of CUMS rats was significantly inhibited by taurine. In vitro study, cell viability, Brdu+, ß-tubulin III+, and GFAP+ cells in taurine-treated cells were significantly higher, while apoptosis rate was lower than the glutamate-treated cells. The protein expression of BDNF and its downstream pathway was upregulated by taurine administration. The results demonstrated that taurine can increase the survival, proliferation, and differentiation of NSCs; this protective effect of taurine may be due to the upregulation of BDNF/ERK/CREB signaling pathway. On the other hand, taurine can also inhibit abnormal apoptosis induced by CUMS or glutamate, the mechanism of which may be due to its antioxidative ability.

Intervention Effect of Taurine on LPS-Induced Intestinal Mechanical Barrier Injury in Piglets.

Taurine has the advantages of being safe, highly efficient, chemically stabile, and biologically active, together with having versatile functions. Presently, it is employed as a veterinary feed additive in animal research. The tight junctions that constitute the intestinal epithelial cells are the most critical structures for ensuring regular and uninterrupted digestion and absorption of food by the intestinal mucosa, while at the same time resisting invasions by toxins. The purpose of this study was to investigate the protective effect and mechanism of taurine action on intestinal mechanical barrier function of piglets that were infected with LPS. The results showed that 0.3% taurine inhibits LPS-driven increase in intestinal permeability and intestinal mucosal injury, the rise in the ratio of villus length to crypt depth within the duodenum, jejunum, and ileum, and the significant enhancement in the expression of tight junction protein-related genes. In summary, dietary taurine significantly reduces intestinal mucosal structural damage and intestinal mucosal permeability while increasing gene expression of tight junction proteins of the intestinal mucosa of piglets induced by LPS, thereby enhancing the effect of intestinal mucosal mechanical barriers.

Biological Effects of Hypomagnetic Field: Ground-Based Data for Space Exploration.

The future of mankind is tied to the exploration and eventual colonization of space. Currently, people have resided in orbit at a space station. In the future, we will have opportunities to stay on the moon, Mars, or in deeper space, where astronauts are exposed to the hypomagnetic field (HMF), which refers to an extremely weak magnetic field environment compared with the geomagnetic field. However, the potential risks of HMF exposure to human health are often overlooked. Here, we summarize the literature related to the biological effects of HMF and calculate the magnitude of the effect. Briefly, HMF impairs multiple animal systems, especially in the central nervous system. Additionally, HMF is a stress factor in plant growth and reproduction. Finally, HMF combined with other space environments, such as radiation and microgravity, can affect organisms. Further studies are required to explore (i) countermeasures to the adverse effects of HMF, (ii) combined effects of HMF with other factors, and (iii) the intensity-effect relationship. © 2021 Bioelectromagnetics Society.

Static Magnetic Field (2-4 T) Improves Bone Microstructure and Mechanical Properties by Coordinating Osteoblast/Osteoclast Differentiation in Mice.

Static magnetic field (SMF), with constant magnetic field strength and direction, has a long history of basic and clinical research in bone biology. Numerous studies demonstrate that exposure to moderate SMF (1 mT-1 T) can increase bone mass and bone density. However, few studies pay attention to the effects of high SMF (>1 T) on the skeletal system. To investigate the physiological effects of high SMF on bone, mice were exposed to 2-4 T SMF for 28 days. Bone microstructure and mechanical properties were examined. The activity of osteoblasts and osteoclasts involved in bone remodeling was evaluated in vivo and in vitro. Compared with the unexposed group, 2-4 T significantly improved the femoral microstructure and tibial mechanical properties. For bone remodeling in vivo, the number of osteoblasts and bone formation was increased, and the osteoclastic number was decreased by 2-4 T. Moreover, the expression of marker proteins in the femur and concentrations of biochemical indicators in serum involved in bone formation were elevated and bone resorption was reduced under 2-4 T SMF. In vitro, osteoblast differentiation was promoted, and the osteoclastic formation and bone resorption ability were inhibited by 2 T SMF. Overall, these results demonstrate that 2-4 T SMF improved bone microarchitecture and strength by stimulating bone formation and restraining bone resorption, and imply that high SMF might become a potential biophysical treatment modality for bone diseases with abnormal bone remodeling. Bioelectromagnetics. © 2021 Bioelectromagnetics Society.

Investigation on the urea deposit formation and thermal decomposition characteristics in the SCR aftertreatment system of a diesel engine.

Selective catalytic reduction is the most efficient and reliable equipment for NOx control in current diesel engines. However, the issue of urea crystallization becomes increasingly serious with the implement of the new emissions standards. In this paper, urea deposit samples collected from engine test bed and tube furnace were characterized by thermogravimetric analysis and Fourier transform-infrared analysis to aid the comprehension of urea deposit formation. Moreover, thermogravimetric tests were conducted to disclose the effects of catalyst on the thermal decomposition processes of urea deposit. The results indicated that less temperature resistant species are formed in the engine test bed than in the tube furnace at conditions with the same temperatures. The main compositions in the World Harmonized Transient Cycle (WHTC) urea deposits are urea, cyanuric acid (CYA) and ammelide, implying that accelerating the decomposition of these species could prevent the accumulation of urea deposit. CuWTi, Cuß and CuZSM catalysts could lead to increased yield of CYA during pure urea thermolysis. Cuß, CuWTi and VWTi catalysts tend to promote the thermolysis of CYA while VWTi has the most significant catalytic effects on the thermal decomposition of ammelide and ammeline.

Iron Overload-Induced Osteocyte Apoptosis Stimulates Osteoclast Differentiation Through Increasing Osteocytic RANKL Production In Vitro.

Iron overload is closely associated with osteoporosis, the potential cellular mechanism involved in decreased osteoblast differentiation and increased osteoclast formation. However, the effect of iron overload on the biological behavior in osteocytes has not been reported. This study aims to investigate the changes of osteocytic activity, apoptosis, and its regulation on osteoclastogenesis in response to iron overload. MLO-Y4 osteocyte-like cells and primary osteocytes from mice were processed with ferric ammonium citrate (FAC) and deferoxamine (DFO), the conditioned medium (CM) was harvested and co-cultured with Raw264.7 cells and bone marrow-derived macrophages (BMDMs) to induce them to differentiate into osteoclasts. Osteocyte apoptosis, osteoclast differentiation, osteocytic gene expression and protein secretion of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) was examined. Excessive iron has a toxic effect on MLO-Y4 osteocyte-like cells. Increased cell apoptosis in MLO-Y4 cells and primary osteocytes was induced by iron overload. The osteoclastic formation, differentiation-related gene expression, and osteoclastic bone-resorption capability were significantly increased after treated with the CM from iron overload-exposed osteocytes. Excessive iron exposure significantly promoted the gene expression and protein secretion of the RANKL in MLO-Y4 cells. Addition of RANKL-blocking antibody completely abolished the increase of osteoclast formation and bone resorption capacity induced by the CM from osteocytes exposed to excessive iron. Moreover, the pan-caspase apoptosis inhibitor, QVD (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methylketone) was used to inhibit osteocyte apoptosis. The results showed osteocyte apoptosis induced by iron overload was reduced by QVD and accompanied by the decrease of soluble RANKL (sRANKL) in supernatant. The increase of osteoclast formation and bone resorption capacity induced by the CM from osteocytes exposed to excessive iron was significantly decreased by QVD. These results indicated that iron overload-induced osteocyte apoptosis is required to regulate osteoclast differentiation by increasing osteocytic RANKL production. This study, for the first time, reveals the indirect effect of iron overload on osteoclast differentiation through regulating osteocytes.

Taurine prevents cardiomyocyte apoptosis by inhibiting the calpain-1/cytochrome c pathway during RVH in broilers.

The calpain-1-activated apoptotic pathway plays a key role in right ventricular hypertrophy (RVH). Taurine has been shown to attenuate apoptosis by inhibiting calpain activity. This experiment aimed to determine whether taurine could prevent RVH by inhibiting the calpain-1/cytochrome c apoptotic pathway. The broilers were given 1% taurine dissolved in drinking water and were raised at 10 °C ~ 12 °C from day 21 to day 42. At 21 d, 28 d, 35 d and 42 d, the right ventricular (RV) tissues were collected. Increased RVH index, angiotensin II, norepinephrine and atrial natriuretic peptide mRNA expression were reduced by taurine in the broiler RVs. Taurine obviously inhibited cardiomyocyte apoptosis via maintaining the mitochondrial membrane potential and decreased the activation of caspase-9 and caspase-3 in the broiler RVs. The antioxidant assay demonstrated that taurine enhanced the activities of superoxide dismutase, total antioxidant capacity and glutathione peroxidase and the glutathione/glutathione disulfide ratio. Western blot results revealed that taurine also downregulated the expression of calpain-1 and cytosolic cytochrome c while upregulating the expression of Bcl-2/Bax and mitochondrial cytochrome c in broiler cardiomyocytes during RVH. In summary, we found that taurine could enhance cardiomyocyte antioxidant ability and further prevented cardiomyocyte apoptosis by inhibiting the calpain-1/cytochrome c pathway during RVH in broilers.