Hydrogel platform facilitating astrocytic differentiation through cell mechanosensing and YAP-mediated transcription.

Astrocytes are multifunctional glial cells that are essential for brain functioning. Most existing methods to induce astrocytes from stem cells are inefficient, requiring couples of weeks. Here, we designed an alginate hydrogel-based method to realize high-efficiency astrocytic differentiation from human neural stem cells. Comparing to the conventional tissue culture materials, the hydrogel drastically promoted astrocytic differentiation within three days. We investigated the regulatory mechanism underlying the enhanced differentiation, and found that the stretch-activated ion channels and Yes-associated protein (YAP), a mechanosensitive transcription coactivator, were both indispensable. In particular, the Piezo1 Ca2+ channel, but not transient receptor potential vanilloid 4 (TRPV4) channel, was necessary for promoting the astrocytic differentiation. The stretch-activated channels regulated the nuclear localization of YAP, and inhibition of the channels down-regulated the expression of YAP as well as its target genes. When blocking the YAP/TEAD-mediated transcription, astrocytic differentiation on the hydrogel significantly declined. Interestingly, cells on the hydrogel showed a remarkable filamentous actin assembly together with YAP nuclear translocation during the differentiation, while a progressive gel rupture at the cell-hydrogel interface along with a change in the gel elasticity was detected. These findings suggest that spontaneous decrosslinking of the hydrogel alters its mechanical properties, delivering mechanical stimuli to the cells. These mechanical signals activate the Piezo1 Ca2+ channel, facilitate YAP nuclear transcription via actomyosin cytoskeleton, and eventually provoke the astrocytic differentiation. While offering an efficient approach to obtain astrocytes, our work provides novel insights into the mechanism of astrocytic development through mechanical regulation.

Unraveling the Mechanobiology Underlying Traumatic Brain Injury with Advanced Technologies and Biomaterials.

Traumatic brain injury (TBI) is a worldwide health and socioeconomic problem, associated with prolonged and complex neurological aftermaths, including a variety of functional deficits and neurodegenerative disorders. Research on the long-term effects has highlighted that TBI shall be regarded as a chronic health condition. The initiation and exacerbation of TBI involve a series of mechanical stimulations and perturbations, accompanied by mechanotransduction events within the brain tissues. Mechanobiology thus offers a unique perspective and likely promising approach to unravel the underlying molecular and biochemical mechanisms leading to neural cells dysfunction after TBI, which may contribute to the discovery of novel targets for future clinical treatment. This article investigates TBI and the subsequent brain dysfunction from a lens of neuromechanobiology. Following an introduction, the mechanobiological insights are examined into the molecular pathology of TBI, and then an overview is given of the latest research technologies to explore neuromechanobiology, with particular focus on microfluidics and biomaterials. Challenges and prospects in the current field are also discussed. Through this article, it is hoped that extensive technical innovation in biomedical devices and materials can be encouraged to advance the field of neuromechanobiology, paving potential ways for the research and rehabilitation of neurotrauma and neurological diseases.

Enantioseparation of racemic amlodipine using immobilized ionic liquid by solid-phase extraction.

In this paper, a novel l-glutamate based immobilized chiral ionic liquid (SBA-IL (Glu)) was prepared by chemical bonding method and applied as a solid sorbent for chiral separation of amlodipine. The performance of SBA-IL (Glu) was investigated for the absorption of (S)-amlodipine and separation of amlodipine enantiomer. The static experiment showed that equilibrium adsorption was achieved within 80 minutes, and the saturation adsorptions capacity was 12 mg/g. The complex was then packed in a glass chromatographic column for the separation of amlodipine and the enantiomeric excess (%ee) of (S)-amlodipine reached 24.67%. The immobilized ionic liquids exhibit good reusability, and the separation efficiency remains 18.24% after reused five times, which allows potential scale-up for the chiral separation of amlodipine.

[Treatment of sternoclavicular joint dislocation with sternoclavicular hook plate fixation].

OBJECTIVE: To evaluate the technique and therapeutic effect of sternoclavicular hook plate fixation in treating sternoclavicular joint (SCJ) dislocation. METHODS: From January 2010 to March 2014,6 patients with SCJ dislocation were treated with sternoclavicular hook plate fixation in our hospital. Among the 6 patients, 5 patients were male and 1 patient was female, and the average age was 34 years, ranging from 26 to 48 years. The course of the disease ranged from 3 to 20 days. All the SCJ dislocations were caused by external injury and accompanied with the symptoms of swelling pain and obvious shoulder joint activity restricted in affected side. All SCJ dislocations were anterior dislocation by the diagnosis of X-ray and CT scan. The postoperative curative effect was evaluated according to Rockwood score. RESULTS: All the patients' operative incision were healed well and in good appearance. X-ray showed that the dislocated SCJ was well reduced and the plate was on right position. All the 6 patients were followed up for 4 to 18 months, with an average of 12 months. The results were evaluated according to Rockwood score, 4 got excellent results, 1 good and 1 fair. No fixation loosening, redislocation or side injury such as vessel, nerve or pleura injury were found. CONCLUSION: With sternoclavicular hook plate fixation, SCJ dislocation could be reduced while keeping its amphiarthrodial function and the completeness of the cartilage surface. Sternoclavicular hook plate fixation has advantages of safety and stabilization in fixation, and patients can begin function exercises earlier.

[Surgical treatment of thoracic and lumbar tuberculosis complicated with severe kyphotic deformity and paraplegia].

OBJECTIVE: To explore an method and the effectiveness of surgical treatment of thoracic and lumbar tuberculosis complicated with severe kyphotic deformity (Cobb angle ≥ 55°) and paraplegia. METHODS: Between January 2009 and January 2013, 13 cases of thoracic and lumbar tuberculosis complicated with severe kyphotic deformity and paraplegia were treated by one-stage posterior vertebral column resection (PVCR), debridement, bone grafting, and instrumentation fixation. Of 13 patients, 7 were male and 6 were female with an average age of 23.5 years (range, 14-49 years). The disease duration was 13-38 months (mean, 19 months). The Cobb angle of kyphosis was (65.23 ± 7.95)°. The visual analogue scale score (VAS) was 7.38 ± 0.31. In 13 patients with incomplete paraplegia, 1 case was classified as Frankel grade B, 7 cases as grade C, and 5 cases as grade D. The lesion involved 2 vertebrae bodies in 7 cases (T8, 9 in 1 case, T11, 12 in 2 cases, and T12, L1 in 4 cases), 3 vertebrae bodies in 4 cases (T10-12 in 2 cases, T9-11 in 1 case, and T11-L1 in 1 case), and 4 vertebrae bodies in 2 cases (T4-7 in 1 case and T6-9 in 1 case). Imaging examination showed paravertebral abscess in 10 cases. RESULTS: Healing of incision by first intention was obtained in all patients. The neurological injury and pulmonary infection occurred in 3 cases and 2 cases respectively, which were cured after symptomatic treatment. Thirteen patients were followed up 12-48 months (mean, 17 months). The erythrocyte sedimentation rate restored to normal level in all cases at 3-7 months after operation. All the patients achieved bony fusion at 10-20 months (mean, 14 months) after operation. No fixation loosening, displacement, or fracture occurred during follow-up. Common toxic symptom of tuberculosis disappeared, and there was no recurrence of local tuberculosis. The Cobb angle of kyphosis was corrected to (22.38 ± 1.76)° at 1 week and (22.15 ± 1.83)° at last follow-up, showing significant difference when compared with preoperative one (P < 0.05). There was no significant difference in Cobb angle of kyphosis between at 1 week after operation and at last follow-up (P > 0.05). The Frankel grading was grade B in 1 case, grade C in 10 cases, and grade D in 2 cases at 1 week after operation; and it was grade D in 1 case and grade E in 12 cases at last follow-up; significant differences were found between at pre- and post-operation (P < 0.05), and between at 1 week after operation and at last follow-up (P < 0.05). The VAS score was 4.08 ± 0.76 at 1 week and 0.62 ± 0.14 at last follow-up, showing significant differences between at pre- and post-operation (P < 0.05) and between at 1 week after operation and at last follow-up (P < 0.05). CONCLUSION: One-stage PVCR, debridement, bone grafting, and instrumentation fixation is proved to be successful in treating thoracic and lumbar tuberculosis complicated with severe kyphotic deformity and paraplegia.

[Comparison of clinical effects of total spondylectomy with different procedures in treating lumbar metastatic tumor].

OBJECTIVE: To compare the therapeutic effects of debris spondylectomy, piecemeal spondylectomy, total en bloc spomdylectomy in treating lumbar metastatic tumors. METHODS: The clinical data of 20 patients with lumbar metastatic tumors treated from January 2008 to October 2013 were retrospectively reviewed. There were 8 males and 12 females, aged from 35 to 65 years old with an average of (49.50 ± 9.97) years. All patients had single solitary metastases. Four cases were in L1,5 cases in L2,4 cases in L3,4 cases in L4, and 3 cases in L5. According to the type of Tomita, type II had in 4 cases, type III in 6 cases, type IV in 6 cases, type V in 4 cases. Tokuhashi score was 12.50 ± 1.97. All patients complained with back or leg pain, VAS score was 8.13 ± 0.85. Among patients, 7 cases were treated with debris spondylectomy (group A), 7 cases with piecemeal spondylectomy (group B), 6 cases with total en bloc spondylectomy (group C). Statistical analysis was used to compare the three groups with respect to surgical trauma (including operative time, transoperative bleeding, and intraoperative blood transfusion), clinical symptoms (by VAS score at 1 week after operation), surgical procedures conditions (by AP and lateral X-rays), and long-term results (by recurrence and death information). RESULTS: All patients were followed up from 6 to 36 months with an average of (16.50 ± 7.88) months. Operative time for debris spondylectomy was (6.14 ± 0.68) h, intraoperative bleeding was (3 457.14 ± 399.40) ml, and intraoperative blood transfusion was (2 771.43 ± 423.14) ml. Operative time for piece-meal spondylectomy was (4.93 ± 0.61) h, intraoperative bleeding was (1 942.86 ± 378.51) ml, and intraoperative blood transfusion was (1 500.00 ± 336.65) ml. Operative time for total en bloc spondylectomy was(4.17 ± 0.67) h, intraoperative bleeding was (1 341.67 ± 361.13) ml, and intraoperative blood transfusion was (916.67 ± 321.66) ml. There was significant differences in operative time, intraoperative blood loss, and intraoperative blood transfusion between three groups (P < 0.05). In terms of these factors, total en bloc spondylectomy had the best outcome followed by piecemeal spondylectomy. All pains had released, VAS score decreased obviously at 1 week after operation (P < 0.05), and there was no significant differences between three groups (P > 0.05). Surgical effects were well with these methods according to the evaluation of AP and lateral X-rays . At final follow-up, group A had 4 recurrences (2 with breast cancer, 1 with prostate cancer,and 1 with thyroid cancer) and 3 deaths (2 with lung cancer and 1 with thyroid cancer); group B had 2 recurrences (1 with breast cancer and 1 with prostate cancer) and 3 deaths (1 with lung cancer, 1 with breast cancer and 1 with kidney cancer);group C had no recurrences and 2 deaths for lung cancer. There was significant differences in recurrence and death between three groups (P < 0.05). In terms of these factors, total en bloc spondylectomy had the best outcome in three methods. CONCLUSION: Three kinds of operation method can relieve pain, improve nerve function, increase the spinal stability, control the local lesions, improve the patient's quality of life in treating lumbar metastatic tumors, but total en bloc spendylectomy, respect to operative time, transoperative bleeding, intraoperative blood transfusion, tumor recurrence and death is clearly superior to other two methods.

[Preparation of basic fibroblast growth factor chitosan microsphere and its properties].

OBJECTIVE: To study the release properties of basic fibroblast growth factor (bFGF) chitosan microspheres prepared by cross-linking-emulsion method using chitosan as a carrier material so as to lay a foundation for further study. METHODS: Using 0.6% sodium tripolyphosphate solution as a crosslinking agent and 1.5% solution of chitosan as a carrier material, bFGF chitosan microspheres were prepared by cross-linking-emulsion method. Laser particle size analyzer and Zeta electric potential analyzer were used to measure the particle diameter distribution, scanning electronic microscope to observe the morphology, and ELISA to determine the drug loading, the encapsulation rate, and the drug release properties. RESULTS: The particle size of bFGF chitosan microspheres ranged 20.312-24.152 microm. The microspheres were round with a smooth surface and uniform distribution, and it had no apparent porosity. The drug loading and encapsulation rate of microspheres were (7.57 +/- 0.34) mg/g and 95.14% +/- 1.58%, respectively. The bFGF chitosan microspheres could continuously release bFGF for 24 days; the bFGF level increased gradually with time and reached (820.45 +/- 21.34) ng/mL at 24 days; and the microspheres had a burst effect, and the burst rate was 18.08%, and the accumulative release rate of the microspheres reached 82.05% during 24 days. CONCLUSION: It is easy-to-operate to prepare the bFGF chitosan microspheres with the cross-linking-emulsion method. The bFGF chitosan microspheres have smooth surface, uniform distribution, and no apparent porosity.

[Surgical treatment of thoracic ossification of ligamentum flavum and therapeutic effects analysis].

OBJECTIVE: To investigate the surgical treatment of thoracic ossification of the ligamentum flavum (TOLF) and analysis of the therapeutic effects. METHODS: Six patients with thoracic ossification of the ligamentum flavum were retrospectively studied from October 2006 to October 2009. All of the patients in this group were treated by en bloc hemi-articular process laminectomy. There were 4 males and 2 females, ranging in age from 45 to 66 years, averaged 55.2 years. The evaluate factors including the preoperative and postoperative JOA scores,and the function of the urinary bladder were analyzed. RESULTS: All the 6 patients were followed after operation. The mean followed-up duration was 10.5 months, ranging from 2 to 18 months. According to JOA evaluation criteria, 4 patients got an excellent result, 1 good and 1 bad. The one patient with bad result had spinal cord compressed for too long time, and the T2-weight MRI showed nonreversible degeneration of spinal cord and combined with schizophrenia. The clinical symptoms improved with varying degrees. CONCLUSION: The en bloc hemi-articular process laminectomy is an effective method for ossification of the thoracic ligamentum flavum. A thorough decompression and real-time protection of the spinal cord is the key to the success of surgery.

A new organically templated vanadium tellurite: (H2dien)[(VO2)(TeO3)]2.2H2O (dien is diethylenetriamine).

A new organically templated vanadium tellurite, poly[2,2'-iminodiethanaminium [hexa-mu2-oxido-tetraoxidoditellurium(IV)divanadium(V)] dihydrate], {(C4H15N3)[Te2V2O10].2H2O}n, features the interconnection of distorted [VO5] trigonal bipyramids by bridging [TeO3] pyramids, leading to a two-dimensional corrugated anionic layer with an interlayer distance of about 13.47 A. The interlayer space is occupied by doubly protonated diethylenetriamine cations (H2dien) and guest water molecules. The two terminal amino groups of H2dien are protonated, while the middle amino group, located on a twofold rotation axis, is not protonated. All the three amino groups and water molecules are involved in hydrogen-bonding interactions. The compound represents a new member in the series (H2am)[(VO2)(TeO3)]2.xH2O, where H2am represents a doubly protonated diamine. Similarities and differences between the structures of members of the series are discussed.

New organically templated vanadium tellurites: (H2pn)[V2TeO8] (pn is propane-1,3-diamine).

The title compound, poly[propane-1,3-diaminium hexa-mu-oxido-dioxidotellurium(IV)divanadium(V)], (C3H12N2)[V2O8Te] or (H2pn)[V2TeO8] (pn is propane-1,3-diamine), contains a two-dimensional anionic layer and the diprotonated pn cation for charge compensation. The anionic layer consists of pyrovanadates and [TeO3] pyramids, which are linked alternately through corner-sharing to form a one-dimensional chain. These one-dimensional chains are crosslinked through two weak Te-O bonds, constructing an anionic layer. Hydrogen bonds are observed involving the diprotonated pn cation and the O atoms of the anionic framework.

catena-Poly[zinc(II)-µ(3)-{hydrogen [1-hydr-oxy-2-(3-pyridinio)ethane-1,1-di-yl]diphospho-nato}].

In the polymeric title compound, [Zn(C(7)H(9)NO(7)P(2))](n), the zinc(II) centre displays a tetra-hedral coordination geometry provided by four O atoms from three different phospho-nate groups. The crystal structure consists of ladder chains parallel to the b axis built up from vertex-sharing of ZnO(4) and PO(3)C tetra-hedra. The chains are linked by strong intra- and inter-chain O-H⋯O and N-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular assembly.

Diaqua-bis(2,2'-biimidazole)cobalt(II) 4,4'-dicarboxy-biphenyl-3,3'-di-car-boxylate.

In the title compound, [Co(C(6)H(6)N(4))(2)(H(2)O)(2)](C(16)H(8)O(8)), the Co(II) cation and the organic anion occupy different crystallographic inversion centres and, as a consequence, the asymmetric unit comprises two half-mol-ecules. The benzene groups are coplanar. The four coordinating N atoms of the two bidentate biimidazole ligands define the equatorial plane of a slightly distorted octa-hedral CoO(2)N(4) geometry, and the water O atoms lie in the axial coordination sites. Translational (a,) and inversion-related symmetry operations link the Co complex mol-ecules and the negatively charged carboxyl-ate anions via inter-molecular N-H⋯O and O-H⋯O hydrogen bonds into sheets parallel to (01). The coordinated water mol-ecules connect the sheets through O-H⋯O hydrogen bonds, forming a three-dimensional framework. In addition, two intra-molecular O-H⋯O hydrogen bonds are observed between the carboxyl and carboxyl-ate groups.