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Objective: To introduce a self-designed adjustable operation frame and explore the feasibility and safety in the treatment of severe kyphosis secondary to ankylosing spondylitis with posterior osteotomy., Methods: Between March 2016 and May 2018, 7 cases of severe kyphosis secondary to ankylosing spondylitis were treated with posterior osteotomy using self-designed adjustable operation frame with prone position. There were 5 males and 2 females with an average age of 49.4 years (range, 40-55 years). The disease duration was 10-21 years (mean, 16.7 years). The apical vertebrae of kyphosis were located at T 11 in 2 cases, T 12 in 1 case, L 1 in 1 case, and L 2 in 3 cases. Among the 7 cases, 2 were classified as typeⅠ, 4 as type ⅡB, and 1 as type ⅢA according to 301 classification system. There was no neurological deficit of all cases; but 1 case suffered bilateral hip joints ankylosed in non-functional position. The parameters of chin-brow vertical angle (CBVA), global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA) were measured; and the operation time, the intraoperative blood loss, and the complications were also collected and analyzed., Results: All operations completed successfully. The operation time was 310-545 minutes (mean, 409.7 minutes) and the intraoperative blood loss was 1 500-2 500 mL (mean, 1 642.9 mL). There were 2 cases treated with one-level osteotomy of sagittal translation, 1 case of radiculopathy symptom of L 3 , and 3 cases of tension of abdominal skin. All patients were followed up 20-35 months (mean, 27.9 months). There were significant differences in CBVA, GK, TLK, LL, and SVA between pre- and post-operation ( P <0.05); but no significant difference between 1 week after operation and last follow-up ( P >0.05). All the osteotomies and bone grafts fused well and no complications of loosening and breakage of internal fixator occurred during the follow-up., Conclusion: In the posterior osteotomy for correction of severe kyphosis secondary to ankylosing spondylitis, the self-designed adjustable operation frame is convenient for the patient to be placed in prone position. It is safe, feasible, and effective to perform osteotomy correction with the aid of the self-designed adjustable operation frame.

Synthetic progestin norethindrone (NET) widely used in oral contraceptives, hormonal therapy and livestock farming has been detected in various aquatic ecosystems. Recent studies have shown that NET can cause thyroid endocrine disruption in amphibians. However, studies are still lacking on thyroid axis of fish. In the present study, we investigated thyroid hormone levels (T3 and T4) and transcriptional patterns of 15 genes of the hypothalamic-pituitary-thyroid axis (HPT axis) in adult zebrafish that were exposed to solvent control and three measured concentrations of NET (7, 84 and 810 ng/L) for 90 days. The results indicated that NET significantly lowered T3 and T4 levels in both female and male zebrafish. Transcriptional expression profiles of some of the HPT-axis related genes were disrupted. Specifically, the expression levels of tshb and pax8 have increased significantly while dio2 and ugt1ab have decreased in females. In male, however, tshb expression levels were increased while ttr, ugt1ab, thra and thrb were decreased. The overall results demonstrate that NET disrupts thyroid endocrine system by interfering at multiple sites along HPT axis in adult zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ischemic tolerance in the brain can be induced by transient limb ischemia, and this phenomenon is termed remote ischemic preconditioning (RIPC). It still remains elusive how this transfer of tolerance occurs. Exosomes can cross the blood-brain barrier, and some molecules may transfer neuroprotective signals from the periphery to the brain. Serum miRNA-126 is associated with ischemic stroke, and exosomal miRNA-126 has shown protective effects against acute myocardial infarction. Therefore, this study aims to explore whether exosomal miRNA-126 from RIPC serum can play a similar neuroprotective role. Exosomes were isolated from the venous serum of four healthy young male subjects, both before and after RIPC. Exosomal miRNA-126 was measured by real-time PCR. The miRNA-126 target sequence was predicted by bioinformatics software. SH-SY5Y neuronal cells were incubated with exosomes, and the cell cycle was analyzed by flow cytometry. The expression and activity of DNA methyltransferase (DNMT) 3B, a potential target gene of miRNA-126, were examined in SH-SY5Y cells. The cell viability of SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD) was also investigated. To confirm the association between miRNA-126 and DNMT3B, we overexpressed miRNA-126 in SH-SY5Y cells using lentiviral transfection. miRNA-126 expression was upregulated in RIPC exosomes, and bioinformatics prediction showed that miRNA-126 could bind with DNMT3B. DNMT levels and DNMT3B activity were downregulated in SH-SY5Y cells incubated with RIPC exosomes. After overexpression of miRNA-126 in SH-SY5Y cells, global methylation levels and DNMT3B gene expression were downregulated in these cells, consistent with the bioinformatics predictions. RIPC exosomes can affect the cell cycle and increase OGD tolerance in SH-SY5Y cells. RIPC seems to have neuroprotective effects by downregulating the expression of DNMTs in neural cells through the upregulation of serum exosomal miRNA-126., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Translaminar percutaneous endoscopic discectomy (PED) was used widely in the treatment of lumbar disc herniation (LDH), especially for the training of novice surgeons. A larger range of osteotomy was a suitable method to get enough operation space and reduce intraoperative risks. But osteotomy, especially facetectomy, may be associated with the biomechanical deterioration and resulting adjacent segment diseases (ASD). Hence, the objects of this study were to investigate whether different levels of surgical experience in performing different ranges of osteotomy (especially facetectomy) affected the risk for ASD and to identify the safe indications for the training of PED novice surgeons. Study Design . In this study, a three-dimensional lumbosacral model was constructed and validated. Corresponding translaminar PED models with different ranges of osteotomy for armpit, periradicular, and shoulder types of LDH were constructed. The von Mises stress on the endplates, the shear stress on the annulus, the intradiscal pressure, and the range of motion (ROM) in the L3-L4 segment disc were computed., Results: Computational results in our well-validated model indicated that large ranges of osteotomy led to deterioration in most of the biomechanical indicators, and this trend was most significant in the shoulder-type LDH model., Conclusions: To ensure the appropriateness of the surgical prognosis, armpit and periradicular types of LDH can be seen as suitable indications for the training of novice PED surgeons, and shoulder-type LDH should be excluded from such indications until novices can perform PED within a relatively small range of osteotomy. Mini Abstract . Based on biomechanical variations in our finite element analysis, armpit and periradicular types of LDH can be seen as suitable indications for the training of novice PED surgeons, and shoulder-type LDH should be excluded until novices can perform PED within a relatively small range of osteotomy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jingchi Li et al.)

Background: (+)-Nootkatone is a highly valued sesquiterpenoid compound, exhibiting a typical grapefruit aroma and various desired biological activities for use as aromatics and pharmaceuticals. The high commercial demand of (+)-nootkatone is predominately met by chemical synthesis, which entails the use of environmentally harmful reagents. Efficient synthesis of (+)-nootkatone via biotechnological approaches is thus urgently needed to satisfy its industrial demand. However, there are only a limited number of studies that report the de novo synthesis of (+)-nootkatone from simple carbon sources in microbial cell factories, and with relatively low yield., Results: As the direct precursor of (+)-nootkatone biosynthesis, (+)-valencene was first produced in large quantities in Saccharomyces cerevisiae by overexpressing (+)-valencene synthase CnVS of Callitropsis nootkatensis in combination with various mevalonate pathway (MVA) engineering strategies, including the expression of CnVS and farnesyl diphosphate synthase (ERG20) as a fused protein, overexpression of a truncated form of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (tHMG1), and downregulating the squalene synthase enzyme (ERG9). These approaches altogether brought the production of (+)-valencene to 217.95 mg/L. Secondly, we addressed the (+)-valencene oxidation by overexpressing the Hyoscyamus muticus premnaspirodiene oxygenase (HPO) variant (V482I/A484I) and cytochrome P450 reductase (ATR1) from Arabidopsis thaliana. However, (+)-valencene was predominantly oxidized to β-nootkatol and only minor amounts of (+)-nootkatone (9.66 mg/L) were produced. We further tackled the oxidation of β-nootkatol to (+)-nootkatone by screening various dehydrogenases. Our results showed that the short-chain dehydrogenase/reductase (SDR) superfamily dehydrogenases ZSD1 of Zingiber zerumbet and ABA2 of Citrus sinensis were capable of effectively catalyzing β-nootkatol oxidation to (+)-nootkatone. The yield of (+)-nootkatone increased to 59.78 mg/L and 53.48 mg/L by additional overexpression of ZSD1 and ABA2, respectively., Conclusion: We successfully constructed the (+)-nootaktone biosynthesis pathway in S. cerevisiae by overexpressing the (+)-valencene synthase CnVS, cytochrome P450 monooxygenase HPO, and SDR family dehydrogenases combined with the MVA pathway engineering, providing a solid basis for the whole-cell production of (+)-nootkatone. The two effective SDR family dehydrogenases tested in this study will serve as valuable enzymatic tools in further optimizing (+)-nootkatone production.

The expansion of urban areas due to population increase and economic expansion creates demand and depletes natural resources, thereby causing land use changes in the main cities. This study focuses on land cover datasets to characterize impervious surface (urban area) expansion in select cities from 1993 to 2017, using supervised classification maximum likelihood techniques and by quantifying impervious surfaces. The results indicate an increasing trend in the impervious surface area by 35% in Bishkek, 75% in Osh, and 15% in Jalal-Abad. The overall accuracy (OA) for the image classification of two different datasets for the three cities was between 82% and 93%, and the kappa coefficients (KCs) were approximately 77% and 91%. The Landsat images with other supplementary data showed positive urban growth in all of the cities. The GDP, industrial growth, and urban population growth were driving factors of impervious surface sprawl in these cities from 1993 to 2017.Landscape Expansion Index (LEI) results also provided good evidence for the change of impervious surfaces during the study period. The results emphasize the idea of applying future planning and sustainable urban development procedures for sustainable use of natural resources and their management, which will increase life quality in urban areas and environments.

Examining the drivers of landscape ecological risk can provide scientific information for planning and landscape optimization. The landscapes of the Amu Darya Delta (ADD) have recently undergone great changes, leading to increases in landscape ecological risks. However, the relationships between landscape ecological risk and its driving factors are poorly understood. In this study, the ADD was selected to construct landscape ecological risk index (ERI) values for 2000 and 2015. Based on a geographically weighted regression (GWR) model, the relationship between each of the normalized difference vegetation index (NDVI), land surface temperature (LST), digital elevation model (DEM), crop yield, population density (POP), and road density and the spatiotemporal variation in ERI were explored. The results showed that the ERI decreased from the periphery of the ADD to the centre and that high-risk areas were distributed in the ADD's downstream region, with the total area of high-risk areas increasing by 86.55% from 2000 to 2015. The ERI was spatially correlated with Moran's I in 2000 and 2015, with correlation of 0.67 and 0.72, respectively. The GWR model indicated that in most ADD areas, the NDVI had a negative impact on the ERI, whereas LST and DEM had positive impacts on the ERI. Crop yield, road density and POP were positively correlated with the ERI in the central region of the ADD, at road nodes and in densely populated urban areas, respectively. Based on the findings of this study, we suggest that the ecological constraints of the aforementioned factors should be considered in the process of delta development and protection.

Objective: To explore the safety and preliminary effectiveness of transintervertebral release, bone impaction grafting, and posterior column compressed-closing in the treatment of osteoporotic vertebral fracture combined with moderate to severe spinal kyphosis., Methods: The clinical data of 21 elderly patients with osteoporotic vertebral fracture combined with moderate to severe spinal kyphosis were retrospectively analyzed between March 2016 and November 2017. There were 1 male and 20 females, aged 55-75 years, with an average of 64.8 years. The disease duration was 8-24 months, with an average of 13.1 months. The bone density T value ranged from -3.4 to -2.1, with an average of -2.3. Lesion segments: T 11 in 2 cases, T 12 in 6 cases, L 1 in 8 cases, L 2 in 1 case, T 11, 12 in 1 case, T 12 , L 1 in 2 cases, and T 12 , L 2 in 1 case. Preoperative neurological function was classified according to the American Spinal Injury Association (ASIA): 5 cases of grade D and 16 cases of grade E. All patients underwent transintervertebral release, bone impaction grafting, and posterior column compressed-closing. The effectiveness was evaluated by visual analogue scale (VAS) score and Oswestry dysfunction index (ODI) score before operation, at 3 months after operation, and at last follow-up. The neurological function was assessed by ASIA at last follow-up. Local kyphosis Cobb angle (LKCA), thoracic kyphosis (TK), lumbar lordosis (LL), and sagittal vertebral axis (SVA) were measured on the X-ray films of the full-length lateral spine of the patient before operation, at 1 week after operation, and at last follow-up., Results: No complication such as fracture of internal fixator or nerve injury occurred. LKCA, TK, and SVA were significantly improved at 1 week after operation and at last follow-up ( P <0.05). There was no significant difference between at 1 week after operation and at last follow-up ( P >0.05). There was no significant difference in LL before and after operation ( F =3.013, P =0.057). The VAS and ODI scores were significantly improved at 3 months after operation and at last follow-up, and further improved at last follow-up when compared with the scores at 3 months after operation, showing significant differences between time points ( P <0.05). Five patients with ASIA grade D neurological function recovered to grade E at 6 months after operation., Conclusion: Transintervertebral release, bone impaction grafting, and posterior column compressed-closing for treating osteoporotic vertebral fracture combined with moderate to severe spinal kyphosis has definite effectiveness, strong orthopaedic ability, and minimal trauma, which can effectively restore the sagittal balance of the spine, alleviate pain, and improve the patients' quality of life.

Study Design: Variation in the biomechanical characteristics of intervertebral discs adjacent to the segment disc after undergoing percutaneous transforaminal endoscopic discectomy (PTED) in models with normal and abnormal bone mineral density (BMD) was estimated using the finite element method., Objective: The study investigated the change in the incidence of adjacent segment disease (ASD) after PTED in patients without and with osteoporosis., Backgrounds: PTED has been widely used for treating lumbar disc herniation (LDH); changes in BMD will affect biomechanical characteristics, possibly leading to changes in the incidence of ASD after PTED. However, this issue remains largely unclear., Methods: A non-linear, lumbosacral finite element model was reconstructed based on imaging data and validated using compared values computed by the current model from published and well-validated, in vitro biomechanical experiment studies. Corresponding PTED models with normal and abnormal BMDs were also reconstructed. Shear and von Mises stresses on the annulus fibrosis, the von Mises stress on the endplates in L5-S1 segment discs, and the total deformation of current lumbosacral models were computed in different body positions by changing loading conditions, including flexion, extension, left and right lateral bending, and axial rotation., Results: In most loading conditions, biomechanical characteristics of the lumbosacral segment discs with normal BMDs after PTED slightly increased. However, in the PTED model with osteoporosis, most of the biomechanical characteristics dramatically increased., Conclusion: Osteoporosis leads to the deterioration of biomechanical characteristics in the adjacent segment disc after PTED; this variation may also result in an increase in the incidence of ASD. However, further studies on the interactions between pathological changes are warranted.

Background: We have previously reported that 5-Aza-2-deoxycytidine (5-Aza-cdR) can repress protein serine/threonine phosphatase-1γ (PP1γ) expression and activity in the mouse hippocampus and affect the behaviour of mice in a water maze. It is well known that the phosphorylation of N-methyl-d-aspartate receptor 2B subunit (NR2B) plays a role in behaviour. In this study, we examined whether 5-Aza-cdR affects NR2B phosphorylation at tyrosine 1472 (p-Y1472 NR2B) and whether it affected the responses of the mice in a passive avoidance test., Methods: 5-Aza-cdR (10 μM) was administered to mice via intracerebroventricular injection (i.c.v). The learning and memory behaviour of the mice were evaluated by measuring their response in a step-down type passive avoidance test 24 h after the injection. The mRNA level of NR2B was measured by real-time PCR. NR2B and p-Y1472 NR2B protein expression in the mouse hippocampus was detected by western blot and immunofluorescence. CDK5 activity was detected by the ADP-Glo™ + CDK5/p35 Kinase Enzyme System. To further clarify whether the 5-Aza-cdR effects on behaviour were dependent on cellular proliferation or not, the effect of 5-Aza-cdR on the expression level of NR2B, the phosphorylation level of p-Y1472 NR2B, cell viability and the cell cycle were analysed using the immortalized mouse hippocampal neuronal cells neural cell line HT22 treated with 10 μM 5-Aza-cdR compared with an untreated control group., Results: After injection with 5-Aza-cdR, the behaviour of the mice in the step-down test was improved, while their phosphorylation level of p-Y1472 NR2B was increased and their CDK5 activity was decreased in the hippocampus. In vitro experiments showed 10 μM 5-Aza-cdR increased the p-Y1472 NR2B phosphorylation level with inhibition of cell viability and cell cycle arrest., Conclusions: Our results suggested that the effect of 5-Aza-cdR on behaviour may be related to the increase in phosphorylation of p-Y1472 NR2B in the hippocampus., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Trichoderma reesei holds a high capacity for protein secretion and represents the most important cellulase producer in industry. However, the external signal sensing and intracellular signal transduction during cellulose induction remain unclear. As one of the most pervasive signal transduction pathways in all eukaryotic species, the mitogen-activated protein kinase (MAPK) pathway and its upstream sensing and signaling components are involved in various physiological processes including stress and nutrient sensing. Particularly, the Hog1-type MAPK Tmk3 has been reported to be involved in the cellulase production in T. reesei ., Results: Here we established the physiological role of two upstream regulatory branches, the Sho1 branch and the Sln1 branch, of the Hog1-type Tmk3 pathway in T. reesei . Deletion of Trste20 of the Sho1 branch or repression of Trypd1 of the Sln1 branch reduced the resistance to high salt stress, whereas TrSho1 showed an opposing effect to that of TrSte20 and the identified TrSln1 seemed to be dispensable in the osmotic regulation. The Sho1 and Sln1 branches also participated in the cell wall integrity maintenance and other stress responses (i.e. oxidative and thermo stresses). Notably, TrSho1 and TrSte20 of the Sho1 branch and TrYpd1 of the Sln1 branch were shown to be differentially involved in the cellulase production of T. reesei . Repression of Trypd1 hardly affected cellulase induction, whereas overexpression of Trypd1 resulted in the reduced production of cellulases. Contrary to the case of Trypd1 , repression of Trsho1 or deletion of Trste20 significantly reduced the transcription of cellulase genes., Conclusions: TrSho1 and TrSte20 of the Sho1 branch and TrYpd1 of the Sln1 branch are all involved in general stress responses including hyperosmotic regulation and cell wall integrity maintenance. Moreover, our study revealed that the Sho1 and Sln1 osmosensing pathways are differentially involved in the regulation of cellulase production in T. reesei . The Sho1 branch positively regulated the production of cellulases and the transcription of cellulase genes while TrYpd1 of the Sln1 branch negatively controlled the cellulase production, supporting the crosstalks of osmosensing and nutrient sensing.

In arid and semi-arid areas with sparse vegetation cover, the spatial pattern of surface soil had a definite effect on soil salinity and nutrient flow, which is of highly importance for understanding the processes of land cover change. In this paper, a total of 3 shrub types and 2 soil sampling depths (0-20 and 20-40 cm) in the arid area of oasis-desert transition belt were selected to assess the spatial heterogeneity of soil resources under shrubs. The results showed that different types of shrub had no significant effect on the particle size distribution of soil which was mainly composed of sand and silt, but significant cluster effect was observed under Tamarix ramosissima + bare land shrub. Soils under shrub canopy had significantly higher contents of organic matter, total N and available K, compared to those in open spaces, and presented obvious "fertile island" phenomenon. Shrub types had significant effects on soil salinity, and different cluster effect existed in soils under different shrubs. The heterogeneity of soil resources resulted from a large number of factors, including climate, soil environment, height and extent of shrub canopy, stemflow, existance of other ground cover plants, and so on, many of which were mutually interactive.