Schwann Cell-Derived Exosomes and Methylprednisolone Composite Patch for Spinal Cord Injury Repair.

Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological process involved after injury, synergistic treatments are very urgently needed in clinical practice. We designed a nanofiber scaffold hyaluronic acid hydrogel patch to release both exosomes and methylprednisolone to the injured spinal cord in a non-invasive manner. This composite patch showed good biocompatibility in the stabilization of exosome morphology and toxicity to nerve cells. Meanwhile, the composite patch increased the proportion of M2-type macrophages and reduced neuronal apoptosis in an in vitro study. In vivo, the functional and electrophysiological performance of rats with SCI was significantly improved when the composite patch covered the surface of the hematoma. The composite patch inhibited the inflammatory response through macrophage polarization from M1 type to M2 type and increased the survival of neurons by inhibition neuronal of apoptosis after SCI. The therapeutic effects of this composite patch can be attributed to TLR4/NF-κB, MAPK, and Akt/mTOR pathways. Thus, the composite patch provides a medicine-exosomes dual-release system and may provide a non-invasive method for clinical treatment for individuals with SCI.

Identification of the Potential Genes Regulating Seed Germination Speed in Maize.

Seed germination is the crucial stage in plant life cycle. Rapid and uniform germination plays an essential role in plant development and grain yield improvement. However, the molecular mechanism underlying seed germination speed is largely unknown due to the complexity of the dynamic process and the difficulty in phenotyping. Here, we conducted a time-series comparative transcriptome study of two elite maize inbred lines, 72-3 and F9721, with striking difference in seed germination speed, and identified a major locus underlying maize germination speed through genome-wide association analysis (GWAS) of an F2 segregation population. Comparative transcriptome study identified 12 h after imbibition (HAI) as the critical stage responsible for the variation in germination speed. The differentially expressed genes (DEGs) between 72-3 and F9721 were mainly enriched in metabolic pathways, biosynthesis of secondary metabolites, oxidoreductase activity pathways, hormone signal transduction, and amino acid transporter activity pathways. GWAS revealed that germination speed was controlled by a major locus on chromosome 1 with the leading SNP as AX-91332814, explaining 10.63% of phenotypic variation. A total of 87 proposed protein-coding genes surrounding the locus were integrated with DEGs. Combined with evidence from the gene expression database and gene synteny with other model species, we finally anchored three genes as the likely candidates regulating germination speed in maize. This study provides clues for the further exploration of genes controlling the maize seed germination speed, thus facilitating breeding of rapid germinated elite lines through marker assistant selection.

IRREGULAR POLLEN EXINE2 Encodes a GDSL Lipase Essential for Male Fertility in Maize.

Anther cuticle and pollen exine are two physical barriers protecting plant reproductive cells against environmental stresses; defects in either often cause male sterility. Here, we report the characterization of a male-sterile mutant irregular pollen exine2 (ipe2) of maize (Zea mays), which displays shrunken anthers and no starch accumulation in mature pollen grains. We cloned the causal gene IPE2 and confirmed its role in male fertility in maize with a set of complementary experiments. IPE2 is specifically expressed in maize developing anthers during stages 8 to 9 and encodes an endoplasmic-reticulum-localized GDSL lipase. Dysfunction of IPE2 resulted in delayed degeneration of tapetum and middle layer, leading to defective formation of anther cuticle and pollen exine, and complete male sterility. Aliphatic metabolism was greatly altered, with the contents of lipid constituents, especially C16/C18 fatty acids and their derivatives, significantly reduced in ipe2 developing anthers. Our study elucidates GDSL function in anther and pollen development and provides a promising genetic resource for breeding hybrid maize.

Maize YSL2 is required for iron distribution and development in kernels.

Iron (Fe) is an essential micronutrient and plays an irreplaceable role in plant growth and development. Although its uptake and translocation are important biological processes, little is known about the molecular mechanism of Fe translocation within seed. Here, we characterized a novel small kernel mutant yellow stripe like 2 (ysl2) in maize (Zea mays). ZmYSL2 was predominantly expressed in developing endosperm and was found to encode a plasma membrane-localized metal-nicotianamine (NA) transporter ZmYSL2. Analysis of transporter activity revealed ZmYSL2-mediated Fe transport from endosperm to embryo during kernel development. Dysfunction of ZmYSL2 resulted in the imbalance of Fe homeostasis and abnormality of protein accumulation and starch deposition in the kernel. Significant changes of nitric oxide accumulation, mitochondrial Fe-S cluster content, and mitochondrial morphology indicated that the proper function of mitochondria was also affected in ysl2. Collectively, our study demonstrated that ZmYSL2 had a pivotal role in mediating Fe distribution within the kernel and kernel development in maize.

Expression of cotton PLATZ1 in transgenic Arabidopsis reduces sensitivity to osmotic and salt stress for germination and seedling establishment associated with modification of the abscisic acid, gibberellin, and ethylene signalling pathways.

BACKGROUND: Zinc-finger transcription factors play central roles in plant growth, development and abiotic stress responses. PLATZ encodes a class of plant-specific zinc-finger transcription factor. However, biological functions or physiological mechanism controlled by PLATZ are currently limited. RESULTS: GhPLATZ1 transcripts were considerably up-regulated by NaCl, mannitol, abscisic acid (ABA) and gibberellin (GA) treatments. Transgenic Arabidopsis by ectopic expression of GhPLATZ1 exhibited faster seed germination and higher seedling establishment under salt and mannitol stresses than those of wild type (WT), indicating enhanced osmotic insensitivity in GhPLATZ1 transgenic Arabidopsis. The ABA content in dry seeds of GhPLATZ1 transgenic Arabidopsis was lower than that of WT whereas the ABA content was not changed in germinating seeds under salt stress. Seed germination was faster than but the seedling establishment of transgenic Arabidopsis was similar to WT. Besides, GhPLATZ1 transgenic and WT Arabidopsis exhibited insensitivity to paclobutrazol (PAC), a GA biosynthesis inhibitor, whereas exogenous GA could eliminate the growth difference between GhPLATZ1 transgenic and WT Arabidopsis under salt stress. Moreover, exogenous 1-aminocyclopropane-1-carboxylic acid (ACC), an ethylene precursor, exerted similar effects to GA. Furthermore, ABI4 and ETO1 transcripts were significantly down-regulated, whereas ACS8 was up-regulated in GhPLATZ1 transgenic Arabidopsis under salt stress. CONCLUSIONS: In conclusion, GhPLATZ1 had broad influence in responses to salt and mannitol stresses in transgenic Arabidopsis during seed germination and seedling establishment. The effect of GhPLATZ1 expression in transgenic Arabidopsis might be mediated by the ABA, GA, and ethylene pathways. Thus, this study provided new insights into the regulatory network in response to abiotic stresses in plants.

A PECTIN METHYLESTERASE gene at the maize Ga1 locus confers male function in unilateral cross-incompatibility.

Unilateral cross-incompatibility (UCI) is a unidirectional inter/intra-population reproductive barrier when both parents are self-compatible. Maize Gametophyte factor1 (Ga1) is an intraspecific UCI system and has been utilized in breeding. However, the mechanism underlying maize UCI specificity has remained mysterious for decades. Here, we report the cloning of ZmGa1P, a pollen-expressed PECTIN METHYLESTERASE (PME) gene at the Ga1 locus that can confer the male function in the maize UCI system. Homozygous transgenic plants expressing ZmGa1P in a ga1 background can fertilize Ga1-S plants and can be fertilized by pollen of ga1 plants. ZmGa1P protein is predominantly localized to the apex of growing pollen tubes and may interact with another pollen-specific PME protein, ZmPME10-1, to maintain the state of pectin methylesterification required for pollen tube growth in Ga1-S silks. Our study discloses a PME-mediated UCI mechanism and provides a tool to manipulate hybrid breeding.

Retraction Note: minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses.

Retraction Note: Li et al. Journal of Orthopaedic Surgery and Research (2016) 11:65 DOI https://doi.org/10.1186/s13018-016-0401-2.The authors have retracted this article [1] because of text overlap with a previously published article [2]. All authors agree to this retraction.

MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.

Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-ß. Additionally, EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.

ABNORMAL POLLEN VACUOLATION1 (APV1) is required for male fertility by contributing to anther cuticle and pollen exine formation in maize.

Anther cuticle and pollen exine are the major protective barriers against various stresses. The proper functioning of genes expressed in the tapetum is vital for the development of pollen exine and anther cuticle. In this study, we report a tapetum-specific gene, Abnormal Pollen Vacuolation1 (APV1), in maize that affects anther cuticle and pollen exine formation. The apv1 mutant was completely male sterile. Its microspores were swollen, less vacuolated, with a flat and empty anther locule. In the mutant, the anther epidermal surface was smooth, shiny, and plate-shaped compared with the three-dimensional crowded ridges and randomly formed wax crystals on the epidermal surface of the wild-type. The wild-type mature pollen had elaborate exine patterning, whereas the apv1 pollen surface was smooth. Only a few unevenly distributed Ubisch bodies were formed on the apv1 mutant, leading to a more apparent inner surface. A significant reduction in the cutin monomers was observed in the mutant. APV1 encodes a member of the P450 subfamily, CYP703A2-Zm, which contains 530 amino acids. APV1 appeared to be widely expressed in the tapetum at the vacuolation stage, and its protein signal co-localized with the endoplasmic reticulum (ER) signal. RNA-Seq data revealed that most of the genes in the fatty acid metabolism pathway were differentially expressed in the apv1 mutant. Altogether, we suggest that APV1 functions in the fatty acid hydroxylation pathway which is involved in forming sporopollenin precursors and cutin monomers that are essential for the development of pollen exine and anther cuticle in maize.

Long noncoding RNA MALAT1 promotes cell proliferation through suppressing miR-205 and promoting SMAD4 expression in osteosarcoma.

Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in multiply biological processes including cell development, differentiation, proliferation and invasion. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in osteosarcoma progression is not well known. In this study, we sought to determine the clinical and bilogical role of MALAT1 in osteosarcoma progression. RT-qPCR analysis showed that MALAT1 expression was significantly increased in primary osteosarcoma tissues and cell lines. Kaplan-Meier analysis indicated that patients with high expression of MALAT1 was associated with poor overall survival compared with the low expressing patients. Furthermore, the gain and loss function assay showed that miR-205 was suppressed by MALAT1 in osteosarcoma and this interaction between miR-205 and MALAT1 has reciprocal effects. Cell viability assay showed that MALAT1 promoted MG-63 and SAOS-2 cell growth through suppressing miR-205. Subsequently, the downstream gene SMAD4 was identified as a direct functional target of miR-205, and miR-205 suppressed osteosarcoma cell growth through suppressing SMAD4. Finally, we demonstrated that MALAT1 promoted osteosarcoma progression via a miR-205-SMAD4 axis. In conclusion, we revealed that enhanced MALAT1 expression predicted unfavourable outcome in osteosarcoma and promoted cell proliferation through suppressing miR-205 and activating SMAD4 function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.

Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses.

BACKGROUND: A number of meta-analyses have been carried out to evaluate the effects of minimally invasive surgery (MIS) versus open surgery (OS) for acute Achilles tendon rupture. However, discordant findings were seen in these meta-analyses. The present study, performing a systematic review of overlapping meta-analyses regarding MIS versus OS of acute Achilles tendon rupture, aimed to assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence. METHODS: The literature search was performed to identify systematic reviews comparing MIS with OS for Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors individually evaluated the quality of meta-analysis and extracted data. The Jadad decision algorithm was conducted to ascertain which meta-analysis offered the best evidence. RESULTS: A total of four meta-analyses was included. All these meta-analyses comprised RCTs or quasi-RCTs and were determined as Level-II evidence. The scores of the Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 7 to 10 (median 9.5). The Jadad algorithm indicated that the best meta-analysis should be chosen according to the search strategies and application of selection. A high-quality meta-analysis with more RCTs was chosen, which suggested that there was no statistically significant difference between MIS and OS regarding rerupture rate, tissue adhesion, sural nerve injury, deep infection, and deep vein thrombosis. However, MIS could decrease superficial infection rate, and had a better patient satisfaction for good to excellent outcomes in comparison to OS. CONCLUSIONS: Based on the best available evidence, MIS may be superior to OS for treating acute Achilles tendon rupture. However, due to some limitations, this should be cautiously interpreted, and further high-quality studies are needed.

Fifty top-cited classic papers in orthopedic elbow surgery: A bibliometric analysis.

OBJECTIVE: The number of citations that a paper has received reflects the impact of the article within a particular medical area. Citation analysis concerning the most cited articles have been widely reported in orthopedic surgery and its subspecialties. However, which articles are cited most frequently in orthopedic elbow surgery is unknown. This study aimed to identify and analyze the characteristics of the 50 most cited articles in elbow surgery. METHODS: Science Citation Index Expanded was used to search for citations in 181 journals chosen according to the relevance for elbow publications. The 50 most cited articles in elbow surgery were identified. The title, authors, year of publications, article type, journal source, country, institution, number of citations, decade published, citation density and level of evidence were recorded and analyzed. RESULTS: The 50 most cited articles were published between 1950 and 2010. The 1980s was the most productive decade. The number of citations ranged from 388 to 124. All the articles were written in English and published in nine journals. The majority of articles originated from United States, followed by Canada and United Kingdom. Fracture was the most discussed topic. The majority of the top cited articles were clinical studies, with the remaining basic research. The most common level of evidence was level IV. CONCLUSIONS: Identification of the most cited papers in elbow surgery shows an insight into the historical development of elbow surgery and provides the foundation for further investigations.

Identification and characterization of fructose 1,6-bisphosphate aldolase genes in Arabidopsis reveal a gene family with diverse responses to abiotic stresses.

Fructose 1,6-biphosphate aldolase (FBA) is a key enzyme in plants, which is involved not only in glycolysis and gluconeogenesis in the cytoplasm, but also in the Calvin cycle in plastids. Research on FBAs in various organisms has been reported, but there is none on FBAs in Arabidopsis at the molecular level. In the current study, eight FBA family genes (AtFBA1-8) were identified and analyzed in Arabidopsis thaliana. These genes have a highly conserved aldolase-type TIM barrel domain and a C-terminal peptide, but variable N-terminal peptides. Based on the phylogenetic analysis of FBA protein sequences from Arabidopsis and other plant species, AtFBA family was classified into two subfamilies, including three members (AtFBA1-3) with high similarities to FBAs occurring at plastid, and five (AtFBA4-8) with high similarities to FBAs localized in the cytoplasm. By confocal microscopy analysis with GFP fusion protein, AtFBA3 and AtFBA4 as well as AtFBA6 were observed to be localized in the plastid and cytoplasm, respectively. At least two duplicated gene pairs of AtFBA1 and AtFBA2, as well as AtFBA4 and AtFBA8 were found. Transcript level analysis of AtFBA genes in various tissues revealed the unique and overlapping expression patterns of plastid and cytosol AtFBA genes, suggesting that these genes may function at different stages of plant growth and development. Interestingly, AtFBA1, AtFBA2, AtFBA5 and AtFBA7 showed undetectable expression in roots. The expression patterns of AtFBA genes under different stress conditions suggested that all the members showed different expression patterns in response to stresses, including ABA, NaCl, Cd, abnormal temperature and drought, and, except for AtFBA3, most of the AtFBA genes were significantly responsive to drought stress in roots. Moreover, AtFBA1, AtFBA2, AtFBA5, AtFBA7 and AtFBA8 were induced by at least one of three sugars (sucrose, glucose and fructose) after 24h of treatment. Further functional analyses indicated important clues of AtFBA2, AtFBA6 and AtFBA8 in plant growth, stress responses and development, respectively. Thus these results provide additional knowledge on AtFBA families and their roles.

Measurement of bone alkaline phosphatase and relative study with osteosarcoma.

The objective of this paper is to explore the value of bone alkaline phosphatase (BALP) for diagnosing osteosarcoma, evaluating the effect of the chemotherapy, judging the prognosis and supervising the relapse and metastasis. The immunoassay was used to check the BALP of the blood serum that was from 42 primary osteosarcoma patients. Alkaline phosphatase (ALP) in blood serum was checked with auto biochemistry equipment. The biopsy tissue and the lesion resected in operation were treated with pathology and histological response was counted. The patients were followed up from five months to 49 months with an average of 24.3 months. Eighteen cases relapsed and transferred, among which, 16 of them were dead, and others were survival to the end of the follow-up. BALP was more sensitive than ALP in diagnosing osteosarcoma (P = 0.015). Fifteen cases decreased to normal value in ALP after preoperative chemotherapy, and 34 cases decreased in BALP. Both ALP and BALP in all cases decreased to normal value in post-operative. There was significant difference in positive correlation between the decrease of BALP and the increase of histological response (P = 0.001, r = 0.642). In the follow-up, there was significant difference in BALP between the group of relapse and transfer and the group of free disease survival (P = 0.000). As a check marker in blood serum, BALP, reflecting the process of ossification, has a higher sensitivity than ALP. It has applied value in the diagnosis of osteosarcoma, reflection of the effect of chemotherapy and forecast the prognosis.