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Osteoclasts were over-activated as we age, which leads to bone loss. Src-deficient mice lead to only one phenotype -severe osteopetrosis due to functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCR) have been targets for ∼35% of approved drugs. However, how Src kinase activity is negatively regulated by GPCRs remains largely elusive. Herein we report that Src is dephosphorylated at Tyr 416 by Dusp18 upon GPR54 activation by its natural ligand Kp-10. Mechanically, both active Src and the Dusp18 phosphatase are recruited by GPR54 through the proline/arginine-rich motif (PR motif) in the C terminus, which is dependent on the Gαq signal pathway. As such, Kiss1, Gpr54, Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss. Accordingly, Kp-10 abrogated bone loss by suppressing osteoclasts activity in vivo. Therefore, Kiss1/Gpr54 is a promising therapeutic strategy governing bone resorption through Src dephosphorylation by Dusp18.

The cell division cycle 6 (CDc6) protein has been primarily investigated as a component of the pre-replicative complex for the initiation of DNA replication. Some studies have shown that CDc6 played a critical role in the development of human carcinoma. However, the expression and roles of CDc6 in the central nervous system remain unknown. We have performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of CDc6 expression in spinal cord. Western blot have found that CDc6 protein levels first significantly increase, reach a peak at day 3, and then gradually return to normal level at day 14 after SCI. Double immunofluorescence staining showed that CDc6 immunoreactivity was found in neurons, astrocytes, and microglia. Additionally, colocalization of CDc6/active caspase-3 has been detected in neurons and colocalization of CDc6/proliferating cell nuclear antigen has been detected in astrocytes and microglial. In vitro, CDc6 depletion by short interfering RNA inhibits astrocyte proliferation and reduces cyclin A and cyclin D1 protein levels. CDc6 knockdown also decreases neuronal apoptosis. We speculate that CDc6 might play crucial roles in CNS pathophysiology after SCI.

Osteoporosis is a global bone disease characterized by reduced bone mineral density (BMD) and increased risk of fractures. The risk of developing osteoporosis increases with aging, especially after menopause in women. Discovering the signaling pathways that play a significant role in aging- and menopause-induced osteoporosis should accelerate osteoporosis drug discovery. In this study, we found that bile acid membrane receptor Tgr5 knockout C57BL/6J mice had similar bone mass as wild-type mice during early and middle-age (before 4 months old) bone remodeling; however, Tgr5-/- markedly decreased bone mass in aged (more than 7 months old) and ovariectomized (OVX) mice compared with wild-type mice. Moreover, Tgr5 knockout strongly induced osteoclast differentiation but had no effect on osteoblast activity. Treatment with different TGR5 agonists consistently inhibited osteoclast differentiation. Importantly, our results showed that Tgr5 regulates osteoclastogenesis by the AMP-activated protein kinase (AMPK) signaling pathway, which is a central metabolic pathway involved in the pathophysiology of aging and age-related diseases. The bile acid nuclear receptor FXR is an established regulator of bone metabolism. We screened the derivatives of betulinic acid (BA), a known TGR5 agonist, to identify novel dual agonists of FXR and TGR5. The derivative SH-479, a pentacyclic triterpene acid, could activate both TGR5 and FXR, with a better inhibitory effect on osteoclastogenesis compared with agonists solely activating FXR or TGR5 and additionally enhanced osteoblastogenesis. Furthermore, SH-479 therapeutically abrogated bone loss in C57BL/6J mice through the bone remodeling pathways. Together, our results demonstrate that dual targeting the bile acid membrane receptor TGR5 and nuclear receptor FXR is a promising strategy for osteoporosis. © 2018 American Society for Bone and Mineral Research.

IRF-1, a kind of transcription factor, is expressed in many cell types, except in early embryonal cells. IRF-1 has played an essential role in various physiological and pathological processes, including tumor immune surveillance, viral infection, development of immunity system and pro-inflammatory injury. However, the expression and function of IRF-1 in spinal cord injury (SCI) are still unknown. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IRF-1 expression in the spinal cord. Western blot have shown that IRF-1 protein levels gradually increased, reaching a peak at day 3 and then gradually declined to a normal level at day 14 after SCI. Double immunofluorescence staining showed that IRF-1 immunoreactivity was found in neurons, but not in astrocytes and microglia. Additionally, colocalization of IRF-1/active caspase-3 was detected in neurons. In vitro, IRF-1 depletion, by short interfering RNA, obviously decreases neuronal apoptosis. In conclusion, this is the first description of IRF-1 expression in spinal cord injury. Our results suggested that IRF-1 might play crucial roles in CNS pathophysiology after SCI.

Heavy metals do not degrade and can remain in the environment for a long time. In this study, we analyzed the effects of Cu, Cd, Pb, Zn, Hg, and As, on environmental quality, pollutant enrichment, ecological hazard, and source identification of elements in sediments using data collected from samples taken from Shuangtai tidal wetland. The comprehensive pollution indices were used to assess environmental quality; fuzzy similarity analysis and geoaccumulation index were used to analyze pollution accumulation; correlation matrix, principal component analysis, and clustering analysis were used to analyze pollution source; environmental risk index and ecological risk index were used to assess ecological risk. The results showed that the environmental quality was either clean or almost clean. Pollutant enrichment analysis showed that the four sub-regions had similar pollution-causing metals to the background values of the soil element of the Liao River Plain, which were ranked according to their similarity. Source identification showed that all the elements were correlated. Ecological hazard analysis showed that the environmental risk index in the study area was less than zero, posing a low ecological risk. Ecological risk of the six elements was as follows: As > Cd > Hg > Cu > Pb > Zn.

The characteristics of the P removal sludge were studied in 3 different operation modes (AO, AOA and A2O mode) of the sequencing batch membrane reactor (SBMBRs). The results showed that the sludge P content was positively correlated with the P removal ability. The relative P content of the saturated P uptake sludge was 30.6%, 36.7% and 42.9%, respectively in the 3 modes. PHB was synthesized in anaerobic activated sludge and the polyp-P granules were decreased. The opposite trend appeared in aerobic condition. The amount of PHB change in anaerobic stage was proportional to the P release capacity. The FISH detection showed that the more proportion of PAOs to the whole cell the more P removal ability in the system.

Effects of enhanced ultraviolet B (UV-B, 280-320 nm) on macroalgae have gained particular attention in recent years. We investigated the changes in the growth, physiological and biochemical characteristics of C. ocellatus under UV-B radiation in this study. The results showed that UV-B could inhibit the growth of C. ocellatus (pC. ocellatus were not obvious. The soluble proteins content and MDA content in C. ocellatus were increased by UV-B radiation, and the increase of MDA content was extraordinary significant. The SOD activity and CAT activity were increased when the intensity of UV-B radiation was 7.2 J/m2, while the SOD activity and CAT activity were decreased when the intensity of UV-B radiation was 21.6 J/m2.

Iodometric determination of dissolved oxygen is used as experimental methods, through the determination of oxygen consumption of crude oil, gasoline , diesel , three different types of oil, oxygen consumption of Philippines clams and oxygen consumption of Philippines clams under the conditions of three oil pollution, variations of DO under the conditions of three oil pollution is researched. The results show that oxygen consumption of gasoline> oxygen consumption of diesel oil> oxygen consumption of crude oil. At the same time, oxygen consumption of gasoline changes with time by a big margin, diesel oil comes second, oxygen consumption of crude oil changed slightly with time.

Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, p

Effects of Ulva pertusa Kjellman stress and UV-B radiation on the growth, physiology and biochemistry of Alexandrium tamarense were studied under laboratory conditions. The results demonstrated that U. pertusa stress and UV-B radiation could inhibit the growth of A. tamarense. Physiology and biochemistry of A. tamarense could be affected under U. pertusa stress and UV-B radiation treatment. U. pertusa stress caused the increase in SOD activity and decrease in H2O2 content. As for UV-B radiation, Chl-a content and soluble content were decreased, while H2O2 content, MDA content and SOD activity were increased. With regard to the combined effects of U. pertusa stress and UV-B radiation, Chl-a content and soluble content were decreased, while MDA content and SOD activity were increased. Compared with UV-B radiation, the combined effects of U. pertusa stress and UV-B radiation treatment on the growth, physiological and biochemical were indiscernible.

The transformation from part design model to manufacturing model is the key technology to realize the integration of CAD/CAPP/CAM, and the key factor is the transformation from design model to blank model .a method of generating casting model for cast then machined part is proposed. The methodology is composed of classifying the part surfaces according to manufacturing requirements, constructing a improved EAAG to recognize simple features, filtering the castable simple feature, enveloping the volumetric machining features containing nonnormal surfaces by means of constructing minimal enveloped auxiliary planes. An example is demonstrated to verify the validity and the effectiveness of the method.

OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three‐dimensional (3‐D) printing model. METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one‐stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26–67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3‐D printing models were created by 3‐D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow‐up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C (4) and C (5) chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks’ management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow‐up. CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3‐D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure.

Although various implants exist for 3- and 4-part fractures, few implants are appropriate for isolated greater tuberosity fractures. This retrospective study evaluated the efficacy of AO X-shaped midfoot locking plates for greater tuberosity fractures. Between May 2008 and September 2009, nineteen patients with displaced greater tuberosity fractures were treated with open reduction and internal fixation using AO X-shaped midfoot locking plates. Postoperatively, radiographs, functional results, and complications were evaluated. All patients were followed up for a mean 33.2 months (range, 24–42 months). Mean healing time was 9.4 weeks (range, 8–14 weeks). Mean Constant score was 90.6±4.0 points (range, 77–95 points). Excellent results were obtained in 16 cases, good in 2 cases, moderate in 1 case, and poor in 0 cases. The excellent-good rate was 94.7%. No recurrence of dislocation occurred in the 11 cases with shoulder dislocation. All fractures healed without the complications of wound infection, skin numbness, subacromial impingement syndrome, nonunion, secondary displacement, and implant loosening. The described technique is an effective, simple, and inexpensive method with a short learning curve.

IRF-1, a kind of transcription factor, is expressed in many cell types, except in early embryonal cells. IRF-1 has played an essential role in various physiological and pathological processes, including tumor immune surveillance, viral infection, development of immunity system and pro-inflammatory injury. However, the expression and function of IRF-1 in spinal cord injury (SCI) are still unknown. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IRF-1 expression in the spinal cord. Western blot have shown that IRF-1 protein levels gradually increased, reaching a peak at day 3 and then gradually declined to a normal level at day 14 after SCI. Double immunofluorescence staining showed that IRF-1 immunoreactivity was found in neurons, but not in astrocytes and microglia. Additionally, colocalization of IRF-1/active caspase-3 was detected in neurons. In vitro, IRF-1 depletion, by short interfering RNA, obviously decreases neuronal apoptosis. In conclusion, this is the first description of IRF-1 expression in spinal cord injury. Our results suggested that IRF-1 might play crucial roles in CNS pathophysiology after SCI.

Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS). This study tried to locate the CNS neuronal elements involved in the innervation of C7 spinal nerve.Pseudorabies virus (PRV, TK/gG(-), 2 microlitre), which expressed green fluorescent protein (GFP), was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats. After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7 segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV.PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.). The number of PRV-labeled neurons in the CNS was increasing with rat's survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.).By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons, which modulates the activity of C7 spinal nerve, is located successfully in the CNS.

It is known that contralateral seventh cervical nerve (C7) root transfer after brachial plexus avulsion injuries (BPAI) causes interhemispheric cortical functional reorganization. However, the potential mechanisms and the role of neurotrophic factors and/or growth-associated protein expression in the process of cerebral reorganization are not well understood. The present study identified the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein 43 (GAP43) mRNA in primary motor cortex after contralateral C7 root transfer following BPAI. BDNF and GAP43 mRNA levels were significantly increased in brain samples at both 6 and 9 months after contralateral C7 root transfer following BPAI, in comparison with the samples from the rats with BPAI only. These findings indicate that BDNF and GAP43 may play an important role during the dynamic transhemispheric functional reorganization.

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. Early excision and grafting reduces cytokines and insulin resistance in burned rats. The authors hypothesized that early wound excision and grafting in patients would also reduce insulin resistance induced by major burn. Thirty-five adult surviving major burn patients (>40%TBSA burn) were recruited. The removal of dead devitalized tissue and allografting in escharectomy group was performed within 72 hours and in control group about 7 days after burn injury. The concentrations of plasma insulin, glucose, and cytokines were measured at 2 and 5 days postburn. Euglycemic-hyperinsulinemic glucose clamps were performed at 5 days after burn. The levels of phosphotyrosine, phosphoserine³¹² of insulin receptor substrate (IRS)-1, and phospho-jun N-terminal kinase (JNK) in muscle were analyzed with immunoprecipitation and Western blotting at 5 days postburn. Escharectomy and allografting during shock stage significantly reduced the levels of interleukin-6 and tumor necrosis factor-α, decreased the levels of phosphoserine³¹² and phospho-JNK, increased the level of phosphotyrosine of IRS-1, and further reduced insulin resistance at 5 days after thermal injury compared with delayed excision group. Escharectomy and allografting during shock stage seemed to have an immunomodulatory effect on the inflammatory mediators and further to reduce insulin resistance induced by major burns in patients by decreasing the phosphorylation of IRS-1 serine³¹² and JNK1/2.

Intensive aquaculture releases large amount of nutrients into aquatic ecosystems and can lead to eutrophication of coastal waters. The effect of salinity and temperature on absorption of ammonium by S. muticum were discussed in this paper. This study was conducted in laboratory to evaluate whether S. muticum could be cultivated efficiently for removing the ammonium from water. The results showed that, the two environmental factors, salinity and temperature, had significant effects on the uptake rates of ammonium. Significant differences in the uptake rates of ammonium among different temperatures or salinities were observed (P

To study the surgical indications, approaches and the clinical results of the total spondylectomy and instrumentation reconstruction in the treatment of cervical spinal tumor.From October 1998 to October 2003, 39 patients with lower cervical bone tumors, including 34 cases with primary tumor and 5 cases with metastatic tumor, were admitted and operated on with total spondylectomy. The patients underwent anteroposterior total spondylectomy including anterior cervical plating, titanium mesh reconstruction and posterior instrumentation based on the location of tumor lesions in the lower cervical spine. One vertebral level total spondylectomy was performed in 29 cases, two level in 7 cases and three level in 3 cases.The postoperative follow-up ranged from 6 months to 4 years. A majority of patients achieved good results postoperatively. Nineteen cases had complete relief of neurological status. One patient died of multiple metastases and systemic failure 24 months later. One case with malignant neurilemmoma developed local recurrence one year postoperatively.Anteroposterior total spondylectomy and reconstruction can reduce local recurrence, improve neurological function and increase operation therapeutic effect. Meanwhile, the technique of cervical total spondylectomy carries relatively greater risks and should be more attention to the operation indication.

To investigate the way of resection of high-sacrum tumors and the way and duration of the spinal-pelvic TSRH or ISOLA internal fixation.From October 1998 through April 2002, 35 patients with sacral tumor were enrolled in our hospital, including 4 cases in L(5)-S(1), 2 in L(5)-S(2), 4 in S(1), 8 in S(1 - 2), 6 in S(1 - 3), 6 in S(1 - 4), 5 in S(1 - 5). 35 patients were followed by lumbo-pelvic TSRH or ISOLA internal fixation and corresponding chemotherapy and radiotherapy.In the follow-up period of 6 - 42 months, the short-term results were satisfactory with the lumbosacral pain reduced and the neurological function improved in different degrees, however dysuria occurred in 1 case and skin necrobiosis at coccygeal incision occurred in 1 case; two cases experienced cerebrospinal fluid leakage and 1 case experienced postoperative infection and delayed healing, 1 case with chordoma and 2 cases with malignant fibrous histiocytoma recurred 1 year after postoperation, one of these 2 cases with malignant fibrous histiocytoma suffered from lung metastasis and died of system failure 19 months after postoperation. No fractured rod occurred.Surgical procedure and postoperative comprehensive treatment have important effects on the prognosis. High-sacral tumor resection and reconstruction are effective means of achieving stabilization, providing significant pain relief and preserving ambulatory capacity.