Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo.

Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor ß-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function.

Glaucocalyxin A suppresses osteoclastogenesis induced by RANKL and osteoporosis induced by ovariectomy by inhibiting the NF-κB and Akt pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Glaucocalyxin A (GLA), the most abundant active component of the aboveground sections of Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara, possesses various pharmacological activities, such as antioxidant, antithrombosis, anticoagulation, antibacterial, antitumor, anti-inflammatory activities. According to previous studies, inflammation is closely associated with osteoclast differentiation and activity. Although GLA has demonstrated effective anti-inflammatory properties, its effects on osteoclast differentiation remain unclear. AIM OF THE STUDY: To examine the possible inhibitory effects of GLA and its molecular mechanisms in osteogenesis induced by RANKL as well as ovariectomy (OVX)-induced osteoporosis (OP) in mice. MATERIALS AND METHODS: Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and a bone resorption pit assay were applied for identifying the effects of GLA on the differentiation of osteoclasts and the function of bone resorption. The mRNA expression of the genes related to osteoclast differentiation was measured by quantitative PCR. Protein expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-fos and phosphorylation of inhibitor of nuclear factor kappa B (IκBα), protein kinase B (AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in RANKL-induced osteoclasts was determined using western blotting. The effect of GLA on OP was studied using a mouse model of OVX. RESULTS: At nontoxic concentrations ≤0.5 µM in vitro, GLA suppressed the formation of osteoclasts induced by RANKL with the decreased number and area size of TRAP-positive multinuclear osteoclasts, and the resorption of bone function by reducing F-actin ring number and bone resorption pit areas. It also reduced the expression of the genes specific for osteoclasts, which included genes encoding NFATc1, cathepsin K, c-fos, TRAP, vacuolar-type ATPase d2, and dendritic cell-specific transmembrane protein. Moreover, GLA repressed NF-κB and Akt pathway activation induced by RANKL. Micro-CT analysis of femur samples indicated decreased bone loss and greater trabecular bone density after GLA treatment, which showed that GLA played a protective role by inhibiting bone loss in OVX-induced OP mice in vivo. CONCLUSIONS: Our study is the first to show that GLA has significant therapeutic potential in OP, which is the disease of osteoclast increase caused by estrogen deficiency.

Development and validation of a nomogram for predicting the probability of nontraumatic osteonecrosis of the femoral head in Chinese population.

Although corticosteroids and alcohol are two major risk factors for nontraumatic osteonecrosis of the femoral head (NONFH), the effects of other factors have rarely been studied, thereby making early diagnosis and treatment of NONFH difficult. This study aimed to develop and validate a nomogram to NONFH, but patients with alcohol- and steroid-related NONFH are not at all taken into account in this study. A training cohort of 790 patients (n = 434, NONFH; n = 356, femoral neck fractures [non-NONFH]) diagnosed in our hospital from January 2011 to December 2016 was used for model development. A least absolute shrinkage and selection operator (lasso) regression model was used for date dimension reduction and optimal predictor selection. A predictive model was developed from univariate and multivariate logistic regression analyses. Performance characterisation of the resulting nomogram included calibration, discriminatory ability, and clinical usefulness. After internal validation, the nomogram was further evaluated in a separate cohort of 300 consecutive patients included between January 2017 and December 2018. The simple prediction nomogram included five predictors from univariate and multivariate analyses, including gender, total cholesterol levels, triglyceride levels, white blood cell count, and platelet count. Internal validation showed that the model had good discrimination [area under the receiver operating characteristic curve (AUC) = 0.80] and calibration. Good discrimination (AUC = 0.81) and calibration were preserved in the validation cohort. Decision curve analysis showed that the predictive nomogram was clinically useful. The simple diagnostic nomogram, which combines demographic data and laboratory blood test results, was able to quantify the probability of NONFH in cases of early screening and diagnosis.

CuMoxW(1-x)O4 Solid Solution Display Visible Light Photoreduction of CO2 to CH3OH Coupling with Oxidation of Amine to Imine.

The photoreduction of carbon dioxide (CO2) to valuable fuels is a promising strategy for the prevention of rising atmospheric levels of CO2 and the depletion of fossil fuel reserves. However, most reported photocatalysts are only active in the ultraviolet region, which necessitates co-catalysts and sacrificial agents in the reaction systems, leading to an unsatisfied economy of the process in energy and atoms. In this research, a CuMoxW(1-x)O4 solid solution was synthesized, characterized, and tested for the photocatalytic reduction of CO2 in the presence of amines. The results revealed that the yield of CH3OH from CO2 was 1017.7 µmol/g under 24 h visible light irradiation using CuW0.7Mo0.3O4 (x = 0.7) as the catalyst. This was associated with the maximum conversion (82.1%) of benzylamine to N-benzylidene benzylamine with high selectivity (>99%). These results give new insight into the photocatalytic reduction of CO2 for valuable chemical products in an economic way.

Expanding Bias-instability of MEMS Silicon Oscillating Accelerometer Utilizing AC Polarization and Self-Compensation.

This paper presents a MEMS (Micro-Electro-Mechanical System) Silicon Oscillating Accelerometer (SOA) with AC (alternating current) polarization to expand its bias-instability limited by the up-converted 1/f noise from front-end transimpedance amplifier (TIA). In contrast to the conventional DC (direct current) scheme, AC polarization breaks the trade-off between input transistor gate size and white noise floor of TIA, a relative low input loading capacitance can be implemented for low noise consideration. Besides, a self-compensation technique combining polarization source and reference in automatic-gain-control (AGC) is put forward. It cancels the 1/f noise and drift introduced by the polarization source itself, which applies to both DC and AC polarization cases. The experimental result indicates the proposed AC polarization and self-compensation strategy expand the bias-instability of studied SOA from 2.58 µg to 0.51 µg with a full scale of ± 30 g, a 155.6 dB dynamic range is realized in this work.

The free neurovascular transverse wrist crease flap for repairing soft tissue defects of the fingers: clinical outcomes of multiple centers.

BACKGROUND: Flap transplantation is often needed for soft tissue defects of the fingers that cannot be closed directly. Sensory reconstruction of the fingers is important for patients to recover feelings. In this study, we report clinical outcomes of using free neurovascular transverse wrist crease flap for repairing finger defects from multiple centers. METHODS: This case series includes 72 consecutive patients with finger defects between June 2013 and June 2016 from multiple centers. A neurovascular transverse free radial artery superficial palmar branch flap, named transverse wrist crease flap, was designed to reconstruct soft tissue defects of the fingers with microvascular anastomosis. When there were soft tissue defects of the fingers with digital nerve defect, end-to-end neurorrhaphy between the median palmar cutaneous branch and the digital nerves was also performed. The donor incision was sutured directly. All the patients were followed-up for more than 24 months. RESULTS: The soft tissue defects of the fingers were all completely covered with this free neurovascular transverse wrist crease flap, and the flaps in 71 patients survived completely without ischemia. Vascular crisis appeared in one case, and the wound healed gradually after changing wound dressing for nearly 1 month. Slight infections of wounds appeared in eight cases. There were no complications in the donor site, like infection and poor wound healing. At the last follow-up, the mean static two-point discrimination was 9.6 ± 2.4 mm on the injured finger and 4.5 ± 0.8 on the contralateral corresponding finger. The motion range of the distal interphalangeal joint and proximal interphalangeal joint on the injured finger were 72.5 ± 23.3% and 78.7 ± 32.5% of the contralateral corresponding finger, respectively. Patient self-evaluations were good in 53 cases and fair in 19 cases. CONCLUSIONS: The results indicate that the free neurovascular transverse wrist crease flap is a good choice for repairing soft tissue defects of the fingers. LEVEL OF EVIDENCE: Therapeutic IV.