[Application of Allgöwer-Donati suture in internal fixation of Schatzker type â ¤and â ¥ tibial plateau closed fractures].

Objective: To investigate the effectiveness of Allgöwer-Donati suture in open reduction and internal fixation of Schatzker type Ⅴ and Ⅵ tibial plateau closed fractures. Methods: A clinical data of 60 patients with Schatzker type type Ⅴ and Ⅵ tibial plateau closed fractures, who met the selection criteria and admitted between May 2022 and May 2023, was retrospectively analyzed. After open reduction and internal fixation via double incisions, the incisions were closed with conventional mattress suture in 30 cases (control group) and Allgöwer-Donati suture in 30 cases (observation group). There was no significant difference in gender, age, fracture side and type, time from injury to operation, body mass index, and other baseline data between the two groups ( P>0.05). The incidence of incision-related complications after operation, visual analogue scale (VAS) score of incision at 3 days and 1 and 2 weeks after operation, and the short-form 36 health survey scale (SF-36) [physical functioning (PF), role physical (RP), bodily pain (BP), and general health (GH)] at 12 weeks after operation were compared between the two groups. Results: All operations of the two groups successfully completed. All patients were followed up 6-14 months (mean, 12 months). Incision fluid leakage occurred in 1 case of observation group and 7 cases of control group within 1 week after operation, and the incisions healed after symptomatic treatment. The incisions of other patients healed by first intention. The incidence of early incision complications in observation group was significantly lower than that in control group ( P<0.05). No late incision complications was found in the two groups. There was no significant difference in VAS scores at each time point between the two groups ( P>0.05). The VAS score significantly decreased with the increase of time in the two groups, showing significant differences between the different time points ( P<0.05). There was no significant difference in SF-36 scores (PF, RP, BP, and GH) between the two groups at 12 weeks after operation ( P>0.05). Conclusion: Compared with conventional mattress suture, Allgöwer-Donati suture is effective in open reduction and internal fixation via double incisions for Schatzker type Ⅴand Ⅵ tibial plateau closed fractures, which can reduce the incidence of early incision complications.

Increase in potato yield by the combined application of biochar and organic fertilizer: key role of rhizosphere microbial diversity.

Purpose: The large-scale planting of potatoes leads to soil degradation, thus limiting the potato yield. An effective method of improving soil quality involves the combined application of biochar and organic fertilizer. However, the proportion of biochar and organic fertilizer at which potato yield can be improved, as well as the improvement mechanism, remain unclear. Methods: A combined application experiment involving biochar (B) and organic fertilizer (O) with four concentration gradients was conducted using the equal carbon ratio method. On this basis, rhizosphere soil fertility, bacterial community composition, and bacterial diversity in potato crops, as well as the potato yield difference under different combined application ratios, were investigated. Then, the direct and indirect effects of these factors on potato yield were analyzed. Results: The results suggest that soil fertility was improved by the combined application of biochar and organic fertilizer, with the best effect being achieved at a ratio of B:O=1:2. The dominant bacterial communities in the potato rhizosphere included Proteobacteria, Actinobacteria, Gemmatimonadetes, Chloroflexi, and Bacteroidetes. When compared to the control, the relative abundance and diversity index of soil bacteria were significantly improved by the treatment at B:O=1:2, which exerted a stronger effect on improving the relative abundance of beneficial bacteria. Soil available phosphorus (AP), soil pH (SpH), and soil organic carbon (SOC) explained 47.52% of the variation in bacterial composition. Among them, the main factor was the content of soil available nutrients, while SpH generated the weakest effect. The bacterial diversity index showed a significant positive correlation with soil AP, SOC, available potassium (AK), total nitrogen (TN), and C/N ratio, and a significant negative correlation with SpH. Bacterial diversity directly affected the potato yield, while soil fertility indirectly affected potato yield by influencing the soil bacterial diversity. Conclusion: The combined application of biochar and organic fertilizer elevates potato yield mainly by improving the diversity of bacterial communities in potato rhizosphere soil, especially the combined application of biochar and organic fertilizer at a 1:2 ratio (biochar 0.66 t ha-1+organic fertilizer 4.46 t ha-1), which made the largest contribution to increasing potato yield.

Effect of Family-Centered Empowerment Model in Home Care of Older Adult Patients After Total Knee Arthroplasty.

PURPOSE: In the present study, we investigated the effect of the family-centered empowerment model (FCEM) in the home care of older adult patients after total knee arthroplasty (TKA). DESIGN: The current study was a randomized controlled study. METHODS: Two hundred eighty older adult patients who underwent TKA in our hospital from December 2020 to December 2022 were selected. They were divided into intervention and control groups using the random number table method, with 140 cases in each group. After follow-up and attrition, 133 patients were assigned to the intervention group and 130 to the control group. The control group received conventional care, and the intervention group received the care provided using the FCEM. The general characteristics of the study subjects were compiled using a general information questionnaire designed by the researcher. The chi-square test and t-test were used to compare the changes in self-care efficacy, knee function, and the occurrence of postoperative complications in the two groups before and after the intervention. FINDINGS: The results suggest that the adoption of FCEM improved patient motivation and self-care efficacy, promoted the recovery of knee function in the short term after surgery, and reduced the likelihood of occurrence of complications. CONCLUSION: The present study highlights the importance of extending the FCEM to multiple domains to fill the gaps in the currently available medical care system for older adults. In addition, the study provides a reference basis for reducing the occurrence of complications and improving patient prognosis. CLINICAL EVIDENCE: The FCEM model is an effective strategy to improve the effectiveness of home nursing for older adults.

Sex specific molecular networks and key drivers of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive and age-associated neurodegenerative disorder that affects women disproportionally. However, the underlying mechanisms are poorly characterized. Moreover, while the interplay between sex and ApoE genotype in AD has been investigated, multi-omics studies to understand this interaction are limited. Therefore, we applied systems biology approaches to investigate sex-specific molecular networks of AD. METHODS: We integrated large-scale human postmortem brain transcriptomic data of AD from two cohorts (MSBB and ROSMAP) via multiscale network analysis and identified key drivers with sexually dimorphic expression patterns and/or different responses to APOE genotypes between sexes. The expression patterns and functional relevance of the top sex-specific network driver of AD were further investigated using postmortem human brain samples and gene perturbation experiments in AD mouse models. RESULTS: Gene expression changes in AD versus control were identified for each sex. Gene co-expression networks were constructed for each sex to identify AD-associated co-expressed gene modules shared by males and females or specific to each sex. Key network regulators were further identified as potential drivers of sex differences in AD development. LRP10 was identified as a top driver of the sex differences in AD pathogenesis and manifestation. Changes of LRP10 expression at the mRNA and protein levels were further validated in human AD brain samples. Gene perturbation experiments in EFAD mouse models demonstrated that LRP10 differentially affected cognitive function and AD pathology in sex- and APOE genotype-specific manners. A comprehensive mapping of brain cells in LRP10 over-expressed (OE) female E4FAD mice suggested neurons and microglia as the most affected cell populations. The female-specific targets of LRP10 identified from the single cell RNA-sequencing (scRNA-seq) data of the LRP10 OE E4FAD mouse brains were significantly enriched in the LRP10-centered subnetworks in female AD subjects, validating LRP10 as a key network regulator of AD in females. Eight LRP10 binding partners were identified by the yeast two-hybrid system screening, and LRP10 over-expression reduced the association of LRP10 with one binding partner CD34. CONCLUSIONS: These findings provide insights into key mechanisms mediating sex differences in AD pathogenesis and will facilitate the development of sex- and APOE genotype-specific therapies for AD.

Extracellular histones, a new class of inhibitory molecules of CNS axonal regeneration.

Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking the major myelin-associated inhibitors do not display spontaneous regeneration after injury, indicating the presence of other inhibitors. Searching for such inhibitors, we have detected elevated levels of histone H3 in human CSF 24 h after spinal cord injury. Following dorsal column lesions in mice and optic nerve crushes in rats, elevated levels of extracellular histone H3 were detected at the injury site. Similar to myelin-associated inhibitors, these extracellular histones induced growth cone collapse and inhibited neurite outgrowth. Histones mediate inhibition through the transcription factor Y-box-binding protein 1 and Toll-like receptor 2, and these effects are independent of the Nogo receptor. Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro, and activated protein C treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS.

MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer's disease pathogenesis.

Our recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP2) homeostasis to the susceptibility of developing Alzheimer's Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP2 pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4+/- patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4-/- subjects. In addition, brain miR-195 levels are reduced along with disease progression from normal aging to early AD, and cerebrospinal fluid (CSF) miR-195 levels of MCI subjects are positively correlated with cognitive performances as measured by mini-mental status examination (MMSE) and negatively correlated with CSF tau levels, suggesting the involvement of miR-195 in early development of AD with a potential impact on cognition. Similar differences in miR-195 levels are seen in ApoE4+/+ mouse hippocampal brain tissue and cultured neurons when compared to ApoE3+/+ counterparts. Over-expressing miR-195 reduces expression levels of its top predicted target synaptojanin 1 (synj1), a brain PIP2-degrading enzyme. Furthermore, elevating miR-195 ameliorates cognitive deficits, amyloid plaque burden, and tau hyper-phosphorylation in ApoE4+/+ mice. In addition, elevating miR-195 rescues AD-related lysosomal defects in inducible pluripotent stem cells (iPSCs)-derived brain cells of ApoE4+/+ AD subjects while inhibiting miR-195 exacerbates these phenotypes. Together, our data uncover a novel regulatory mechanism of miR-195 targeted at ApoE4-associated brain PIP2 dyshomeostasis, cognitive deficits, and AD pathology.

Design, synthesis and evaluation of novel ferulic acid derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease.

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7 nM for hAChE and 0.66 µM for hBuChE) and the good Aß aggregation inhibition (49.2% at 20 µM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.

Advances in developing novel therapeutic strategies for Alzheimer's disease.

Alzheimer's Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is a great need for therapies to prevent and/or slow the progression of AD. The major challenge in AD drug development is lack of clarity about the mechanisms underlying AD pathogenesis and pathophysiology. Several studies support the notion that AD is a multifactorial disease. While there is abundant evidence that amyloid plays a role in AD pathogenesis, other mechanisms have been implicated in AD such as tangle formation and spread, dysregulated protein degradation pathways, neuroinflammation, and loss of support by neurotrophic factors. Therefore, current paradigms of AD drug design have been shifted from single target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects, and from treating AD at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Here, we summarize current strategies and new trends of AD drug development, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanism based, e.g. symptomatic treatments, lifestyle modifications and risk factor management).

Design, synthesis and evaluation of resveratrol-indazole hybrids as novel monoamine oxidases inhibitors with amyloid-ß aggregation inhibition.

Novel hybrids with MAO and Aß (1-42) self-aggregation inhibitory activities were designed and synthesized with the employment of indazole moiety and resveratrol. The biological screening results indicated that most compounds displayed potent inhibitory activity for Aß (1-42) self-aggregation, and obvious selective inhibition to MAO-B. Among these compounds, compound 6e was the most potent inhibitor not only for hMAO-B (IC50 = 1.14 µM) but also for Aß (1-42) self-aggregation (58.9% at 20 µM). Molecular modeling and kinetic studies revealed that compound 6e was a competitive MAO-B inhibitor, which can occupy the active site of MAO-B, and interact with Aß (1-42) via π-π and cation-π stacking interactions. In addition, compound 6e had no toxicity on PC12 cells and could cross the BBB. Collectively, all these results suggested that compound 6e might be a promising multi-target lead compound worthy of further investigation.

Design, synthesis and biological evaluation of novel coumarin-N-benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer's disease.

Combining N-benzyl pyridinium moiety and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activities were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for ChE and Aß (1-42) self-aggregation, and clearly selective inhibition to MAO-B over MAO-A. Of these compounds, compound 7f was the most potent inhibitor for hMAO-B, and it was also a good and balanced inhibitor to ChEs and hMAO-B (0.0373 µM for eeAChE; 2.32 µM for eqBuChE; 1.57 µM for hMAO-B). Molecular modeling and kinetic studies revealed that compound 7f was a mixed-type inhibitor, which bond simultaneously to CAS and PAS of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, compound 7f with no toxicity on PC12 neuroblastoma cells, showed good ability to inhibit Aß (1-42) self-aggregation and cross the BBB. Collectively, all these results suggested that compound 7f might be a promising multi-target lead candidate worthy of further pursuit.

Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease.

A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aß (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC50, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 µM for eqBuChE and 4.4 µM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aß (1-42) aggregation (64.7% at 20 µM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.

Synthesis and evaluation of small molecules bearing a benzyloxy substituent as novel and potent monoamine oxidase inhibitors.

A new series of small molecules bearing a benzyloxy substituent have been designed, synthesized and evaluated for hMAO inhibitory activity in vitro. Most of the compounds were potent and selective MAO-B inhibitors, and were weak inhibitors of MAO-A. In particular, compounds 9e (IC50 = 0.35 µM) and 10e (IC50 = 0.19 µM) were the most potent MAO-B inhibitors, and exhibited the highest selectivity for MAO-B (9e, SI > 285.7-fold and 10e, SI = 146.8-fold). In addition, the structure-activity relationships for MAO-B inhibition indicated that electron-withdrawing groups in the open small molecules were more suitable for MAO-B inhibition, and substitutions at the benzyloxy of the open small molecules, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking studies have been done to explain the potent MAO-B inhibition of the open small molecules. Furthermore, the representative compounds 9e and 10e showed low neurotoxicity in SH-SY5Y cells in vitro. So the small molecules bearing the benzyloxy substituent could be used to develop promising drug candidates for the therapy of neurodegenerative diseases.

Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth.

Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans.

Preparation of highly purified timosaponin AIII from rhizoma anemarrhenae through an enzymatic method combined with preparative liquid chromatography.

Timosaponin AIII (TAIII) exhibits extensive pharmacological activities and has been reported as a potent antitumour agent for various human cancers. In the present study, a potential industrial process for producing TAIII that involves biotransformation directly in the crude extract liquid of rhizoma anemarrhenae (RA) was developed. ß-D-glycosidase was used to transform timosaponin BII (TBII) into TAIII, and monofactor experiments were conducted to optimise the enzymolysis conditions. In addition, AB-8 macroporous resin column chromatography, preparative liquid chromatography, and crystallisation technique were applied for yielding TAIII crystals with a purity > 97%. Approximately, 7 g of TAIII with a high purity of > 97% was obtained from 1 kg of RA through this five-step preparation method, which can be used to produce TAIII on a large scale.

The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells.

Genipin (GNP) effectively inhibits uncoupling protein 2 (UCP2), which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS) levels. In this study, the hydroxyls at positions C10 (10-OH) and C1 (1-OH) of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1) proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP's activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1) and 1-ethyl-genipin (1-GNP2) lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1) and 10-acetic acid-genipin (10-GNP2) exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP's apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.

Metallothionein-I/II Promotes Axonal Regeneration in the Central Nervous System.

The adult CNS does not spontaneously regenerate after injury, due in large part to myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo-A, and oligodendrocyte-myelin glycoprotein. All three inhibitors can interact with either the Nogo receptor complex or paired immunoglobulin-like receptor B. A conditioning lesion of the sciatic nerve allows the central processes of dorsal root ganglion (DRG) neurons to spontaneously regenerate in vivo after a dorsal column lesion. After a conditioning lesion, DRG neurons are no longer inhibited by myelin, and this effect is cyclic AMP (cAMP)- and transcription-dependent. Using a microarray analysis, we identified several genes that are up-regulated both in adult DRGs after a conditioning lesion and in DRG neurons treated with cAMP analogues. One gene that was up-regulated under both conditions is metallothionein (MT)-I. We show here that treatment with two closely related isoforms of MT (MT-I/II) can overcome the inhibitory effects of both myelin and MAG for cortical, hippocampal, and DRG neurons. Intrathecal delivery of MT-I/II to adult DRGs also promotes neurite outgrowth in the presence of MAG. Adult DRGs from MT-I/II-deficient mice extend significantly shorter processes on MAG compared with wild-type DRG neurons, and regeneration of dorsal column axons does not occur after a conditioning lesion in MT-I/II-deficient mice. Furthermore, a single intravitreal injection of MT-I/II after optic nerve crush promotes axonal regeneration. Mechanistically, MT-I/II ability to overcome MAG-mediated inhibition is transcription-dependent, and MT-I/II can block the proteolytic activity of α-secretase and the activation of PKC and Rho in response to soluble MAG.

Soluble adenylyl cyclase is necessary and sufficient to overcome the block of axonal growth by myelin-associated factors.

Neurons in the CNS do not regenerate following injury; regeneration is blocked by inhibitory proteins in myelin, such as myelin-associated glycoprotein (MAG). Elevating neuronal levels of the second messenger cAMP overcomes this blocked axonal outgrowth. One way to elevate cAMP is pretreating neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF). However, pleiotropic effects and poor bioavailability make exogenous administration of neurotrophins in vivo problematic; therefore, alternative targets must be considered. In neurons, two families of adenylyl cyclases synthesize cAMP, transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). Here, we demonstrate that sAC is the essential source of cAMP for BDNF to overcome MAG-dependent inhibition of neurite outgrowth. Elevating sAC in rat and mouse neurons is sufficient to induce neurite outgrowth on myelin in vitro and promotes regeneration in vivo. These results suggest that stimulators of sAC might represent a novel therapeutic strategy to promote axonal growth and regeneration.

Metabolism of Genipin in Rat and Identification of Metabolites by Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Tandem Mass Spectrometry.

The in vivo and in vitro metabolism of genipin was systematically investigated in the present study. Urine, plasma, feces, and bile were collected from rats after oral administration of genipin at a dose of 50 mg/kg body weight. A rapid and sensitive method using ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF MS) was developed for analysis of metabolic profile of genipin in rat biological samples (urine, plasma, feces, and bile). A total of ten metabolites were detected and identified by comparing their fragmentation patterns with that of genipin using MetaboLynx software tools. On the basis of the chromatographic peak area, the sulfated and glucuronidated conjugates of genipin were identified as major metabolites. And the existence of major metabolites G1 and G2 was confirmed by the in vitro enzymatic study further. Then, metabolite G1 was isolated from rat bile by semipreparative HPLC. Its structure was unambiguously identified as genipin-1-o-glucuronic acid by comparison of its UV, IR, ESI-MS, (1)H-NMR, and (13)C-NMR spectra with conference. In general, genipin was a very active compound that would transform immediately, and the parent form of genipin could not be observed in rats biological samples. The biotransformation pathways of genipin involved demethylated, ring-opened, cysteine-conjugated, hydroformylated, glucuronidated, and sulfated transformations.

Secretory leukocyte protease inhibitor reverses inhibition by CNS myelin, promotes regeneration in the optic nerve, and suppresses expression of the transforming growth factor-ß signaling protein Smad2.

After CNS injury, axonal regeneration is limited by myelin-associated inhibitors; however, this can be overcome through elevation of intracellular cyclic AMP (cAMP), as occurs with conditioning lesions of the sciatic nerve. This study reports that expression of secretory leukocyte protease inhibitor (SLPI) is strongly upregulated in response to elevation of cAMP. We also show that SLPI can overcome inhibition by CNS myelin and significantly enhance regeneration of transected retinal ganglion cell axons in rats. Furthermore, regeneration of dorsal column axons does not occur after a conditioning lesion in SLPI null mutant mice, indicating that expression of SLPI is required for the conditioning lesion effect. Mechanistically, we demonstrate that SLPI localizes to the nuclei of neurons, binds to the Smad2 promoter, and reduces levels of Smad2 protein. Adenoviral overexpression of Smad2 also blocked SLPI-induced axonal regeneration. SLPI and Smad2 may therefore represent new targets for therapeutic intervention in CNS injury.

The fabrication of La-substituted bismuth titanate nanofibers by electrospinning.

Bismuth titanates with La-substituted (Bi(3.25)La(0.75)Ti(3)O(12), BLT) nanofibers were synthesized by sol-gel based electrospinning. Pure phase perovskite structure BLT nanofibers could be obtained by annealing at 700 degrees C in air for 1 h. The morphology, crystallized phase and crystal structure were investigated by means of scanning electron microscopy, x-ray diffraction analysis and high resolution transmission electron microscopy, respectively. Nanofibers with fine crystallinity were observed with fiber diameters in the range of 100-300 nm and length over 150 microm. The ferroelectricity of BLT nanofibers has been confirmed by piezoresponse force microscopy. Excellent piezoelectricity of individual nanofibers has also been obtained.