Trends and Opportunities in Organic Synthesis: Global State of Research Metrics and Advances in Precision, Efficiency, and Green Chemistry.

Organic synthesis continues to drive a broad range of research advances in chemistry and related sciences. Another clear trend in organic synthesis research is the increasing desire to target improvements in the quality of life of humankind, new materials, and product specificity. Here, a landscape view of organic synthesis research is provided by analysis of the CAS Content Collection. Three emerging research directions, enzyme catalysis, photocatalysis, and green chemistry in organic synthesis, were identified and featured based on the publication trend analysis.

A combined passivator of zeolite and calcium magnesium phosphate fertilizer: Passivation behavior and mechanism for Cd (II) in composting.

Passivation of heavy metals is one of the most efficient techniques to improve the quality of compost. Many studies confirmed the passivation effect of passivators (e.g., zeolite and calcium magnesium phosphate fertilizer) on cadmium (Cd), but passivators with single component could not effectively passivate Cd in the long-term operation of composting. In the present study, a combined passivator of zeolite and calcium magnesium phosphate fertilizer (ZCP) was used to explore its impacts of adding at different composting periods (heating period, thermophilic period, cooling period) on the Cd control, compost quality (e.g., temperature, moisture content and humification), microbial community structure as well as the compost available forms of Cd and addition strategy of ZCP. Results showed that Cd passivation rate could be increased by 35.70-47.92% under all treatments in comparison to the control treatment. By altering bacterial community structure, reducing Cd bioavailability and improving the chemical properties of the compost, the combined inorganic passivator could achieve high efficiency for Cd passivation. To sum up, the addition of ZCP at different composting periods has effects on the process and quality of composting, which could provide ideas for the optimization of the passivators addition strategy.

How to select the lowest instrumented vertebra in NF-1 non-dystrophic scoliosis.

PURPOSE: To investigate lowest instrumented vertebra (LIV) selection strategy for neurofibromatosis type 1 (NF-1) non-dystrophic scoliosis. METHODS: Consecutive eligible subjects with NF-1 non-dystrophic scoliosis were included. All patients were followed up at least for 24 months. Enrolled patients with LIV in stable vertebra were divided into stable vertebra group (SV group), and the other patients with LIV above the stable vertebra were divided into above stable vertebra group (ASV group). Demographic data, operative data, preoperative and postoperative radiographic data, and clinical outcome were collected and analyzed. RESULTS: There were 14 patients in SV group (ten males and four females, mean age 13.9 ± 4.1 years) and 14 patients in ASV group (nine males and five females, mean age 12.9 ± 3.5 years). The mean follow-up period was 31.7 ± 17.4 months for patients in SV group and 33.6 ± 17.4 months for patients in ASV group, respectively. No significant differences were found in demographic data between two groups. The coronal Cobb angle, C7-CSVL, AVT, LIVDA, LIV tilt and SRS-22 questionnaire outcome significantly improved at the final follow-up in both groups. However, significantly higher loss of correction rate and increasement of LIVDA were found in ASV group. Two patients (14.3%) in ASV group but none in SV group suffered adding-on phenomenon. CONCLUSIONS: Although patients in both SV and ASV groups obtained improved therapeutic efficacy at final follow-up, the radiographic and clinical outcome seemed more likely to deteriorate in ASV group after surgery. The stable vertebra should be recommended as LIV for NF-1 non-dystrophic scoliosis.

Energy spectrum CT index-based machine learning model predicts the effect of intravenous thrombolysis in lower limbs.

To develop a noninvasive machine learning (ML) model based on energy spectrum computed tomography venography (CTV) indices for preoperatively predicting the effect of intravenous thrombolytic treatment in lower limbs. A total of 3492 slices containing thrombus regions from 58 veins in lower limbs in a cohort of 18 patients, divided in good and poor thrombolysis prognosis groups, were analyzed. Key indices were selected by univariate analysis and Pearson correlation coefficient test. A support vector machine classifier-based model was developed through ten-fold cross validation. Model performance was assessed in terms of discrimination, calibration, and clinical usefulness at both per-slice and per-vessel levels. Continuous variables and categorical variables were compared between good and poor thrombolysis prognosis group by Mann-Whitney U-test and chi-square test, respectively. A nomogram was built by integrating clinical factors and the energy spectrum CTV index-based score calculated by the model. Six indices selected from 192 indices were used to build the predictive model. The ML model achieved area under the curves (AUCs) of 0.838 and 0.767 [95% CI (confidence interval), 0.825-0.850, 0.752-0.781] in the training and validation datasets at the per-slice level, and the per-vessel level AUCs were 0.945 and 0.876 (95% CI, 0.852-0.988, 0.763-0.948) in the training and validation datasets, respectively. The nomogram showed better performance with the per-vessel level AUC, accuracy, sensitivity and specificity, yielding 0.901(95% CI, 0.793-0.964), 86.2%, 87.9% and 84.0% in the validation dataset, respectively. There was no significant difference in the vessel distribution between good and poor thrombolysis prognosis groups (chi-square test, p = 0.671). The energy spectrum CTV index-based ML model achieved favorable effectiveness in predicting the outcome of vessel-level intravenous thrombolysis. A nomogram integrating clinical factors, and risk score calculated by the developed model showed improved performance and had potential to be used as a noninvasive preoperative tool for clinicians.

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes.

BACKGROUND: The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known. METHODS: Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. RESULTS: EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. CONCLUSIONS: These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.

Quantitative Automated Segmentation of Lipiodol Deposits on Cone-Beam CT Imaging Acquired during Transarterial Chemoembolization for Liver Tumors: A Deep Learning Approach.

PURPOSE: To show that a deep learning (DL)-based, automated model for Lipiodol (Guerbet Pharmaceuticals, Paris, France) segmentation on cone-beam computed tomography (CT) after conventional transarterial chemoembolization performs closer to the "ground truth segmentation" than a conventional thresholding-based model. MATERIALS AND METHODS: This post hoc analysis included 36 patients with a diagnosis of hepatocellular carcinoma or other solid liver tumors who underwent conventional transarterial chemoembolization with an intraprocedural cone-beam CT. Semiautomatic segmentation of Lipiodol was obtained. Subsequently, a convolutional U-net model was used to output a binary mask that predicted Lipiodol deposition. A threshold value of signal intensity on cone-beam CT was used to obtain a Lipiodol mask for comparison. The dice similarity coefficient (DSC), mean squared error (MSE), center of mass (CM), and fractional volume ratios for both masks were obtained by comparing them to the ground truth (radiologist-segmented Lipiodol deposits) to obtain accuracy metrics for the 2 masks. These results were used to compare the model versus the threshold technique. RESULTS: For all metrics, the U-net outperformed the threshold technique: DSC (0.65 ± 0.17 vs 0.45 ± 0.22, P < .001) and MSE (125.53 ± 107.36 vs 185.98 ± 93.82, P = .005). The difference between the CM predicted and the actual CM was 15.31 mm ± 14.63 versus 31.34 mm ± 30.24 (P < .001), with lesser distance indicating higher accuracy. The fraction of volume present ([predicted Lipiodol volume]/[ground truth Lipiodol volume]) was 1.22 ± 0.84 versus 2.58 ± 3.52 (P = .048) for the current model's prediction and threshold technique, respectively. CONCLUSIONS: This study showed that a DL framework could detect Lipiodol in cone-beam CT imaging and was capable of outperforming the conventionally used thresholding technique over several metrics. Further optimization will allow for more accurate, quantitative predictions of Lipiodol depositions intraprocedurally.

MR Imaging Biomarkers for the Prediction of Outcome after Radiofrequency Ablation of Hepatocellular Carcinoma: Qualitative and Quantitative Assessments of the Liver Imaging Reporting and Data System and Radiomic Features.

PURPOSE: To assess the Liver Imaging Reporting and Data System (LI-RADS) and radiomic features in pretreatment magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in patients with nodular hepatocellular carcinoma (HCC) treated with radiofrequency (RF) ablation. MATERIAL AND METHODS: Sixty-five therapy-naïve patients with 85 nodular HCC tumors <5 cm in size were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, retrospective study. All patients underwent RF ablation as first-line treatment and demonstrated complete response on the first follow-up imaging. Gadolinium-enhanced MR imaging biomarkers were analyzed for LI-RADS features by 2 board-certified radiologists or by analysis of nodular and perinodular radiomic features from 3-dimensional segmentations. A radiomic signature was calculated with the most informative features of a least absolute shrinkage and selection operator Cox regression model using leave-one-out cross-validation. The association between both LI-RADS features and radiomic signatures with PFS was assessed via the Kaplan-Meier analysis and a weighted log-rank test. RESULTS: The median PFS was 19 months (95% confidence interval, 16.1-19.4) for a follow-up period of 24 months. Multifocality (P = .033); the appearance of capsular continuity, compared with an absent or discontinuous capsule (P = .012); and a higher radiomic signature based on nodular and perinodular features (P = .030) were associated with poorer PFS in early-stage HCC. The observation size, presence of arterial hyperenhancement, nonperipheral washout, and appearance of an enhancing "capsule" were not associated with PFS (P > .05). CONCLUSIONS: Although multifocal HCC clearly indicates a more aggressive phenotype even in early-stage disease, the continuity of an enhancing capsule and a higher radiomic signature may add value as MR imaging biomarkers for poor PFS in HCC treated with RF ablation.

How to select the lowest instrumented vertebra in Lenke 5/6 adolescent idiopathic scoliosis patients with derotation technique.

PURPOSE: To introduce and evaluate our lowest instrumented vertebra (LIV) selection criteria for Lenke type 5/6 adolescent idiopathic scoliosis (AIS) patients with de-rotation technique. METHODS: There were 53 eligible Lenke 5/6 AIS patients with minimum 2-year follow-up enrolled in current study. The LIV selection criteria were: (1) the first vertebra touching the central sacral vertical line (CSVL) or the most cephalad vertebra which can return to stable zone under lateral bending position; (2) vertebral rotation no more than grade II by Nash-Moe rotation evaluation; (3) the lowest instrumented vertebra disc angle (LIVDA) could be reversed on lateral bending position. Demographic data, operation data and radiographic data were obtained and analyzed. RESULTS: Both clinical evaluation and radiographic data showed satisfactory outcome. The thoracolumbar/lumbar curve was improved from 53.4 ± 11.0° preoperatively to 6.9 ± 2.6° at the final follow-up. Two patients (3.8%) with adding on and two patients (3.8%) with coronal decompensation were identified at the final follow-up. LIV translation, LIV tilt and LIV disc angle were gradually improved after operation. The preoperative LIV tilt was positively correlated with Cobb angle (p = 0.010) and AVT (p = 0.030) at the final follow-up, and preoperative LIVDA was positively correlated with Cobb angle (p = 0.033) at the final follow-up. CONCLUSION: In Lenke 5/6 scoliosis, the current LIV selection criteria with de-rotation technique contribute to satisfactory correction rate of 87.1% and minimal alignment complications of 7.6%. LIV could be spontaneously and progressively improved after operation. Preoperative LIV tilt and LIVDA could predict postoperative correction and coronal balance.

Sulphur dioxide and fluoride co-exposure induce incisor hypomineralization and amelogenin upregulation via YAP/RUNX2 signaling pathway.

Sulphur dioxide (SO2) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO2 and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO2 and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO2 and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO2 and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO2 and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO2 and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO2 and fluoride may have an increased risk of developing enamel damage.

Quantitative determining of pre-operative osteotomy plan for severe spinal deformity: an analysis of 131 consecutive Yang's A type cases from single center.

PURPOSE: This study aimed to quantify osteotomy protocol for severe spinal deformity correction based on pre-operative demographic, clinical and radiologic parameters. METHODS: A total of 131 Yang's A type severe spinal deformity patients were included. All patients received one of following osteotomies: Ponte/2 (Ponte osteotomy/Grade 2 osteotomy, n = 30), PSO/3 (pedicle subtraction osteotomy/Grade 3 osteotomy, n = 19), BDBO/4 (bone-disc-bone osteotomy/Grade 4 osteotomy, n = 26), SVCR/5 (single-level vertebral column resection/Grade 5 osteotomy, n = 38) and MVCR/6 (multilevel vertebral column resection/Grade 6 osteotomy, n = 18). Demographic, clinical and radiologic characteristics were compared among groups. RESULTS: Tukey's test identified 6 significant variables between paired groups: age for MVCR/6 versus Ponte/2 + PSO/3 + BDBO/4 + SVCR/5 groups; bending Cobb angle for Ponte/2 versus MVCR/6; sagittal deformity angular ratio (S-DAR) for Ponte/2 + PSO/3 versus BDBO/3 + SVCR/5 versus MVCR/6; pre-operative scoliosis for Ponte/2 versus SVCR/5; total-DAR (T-DAR) and pre-operative kyphosis for Ponte/2 + PSO/3 versus BDBO/4 + SVCR/5 + MVCR/6. Receiver Operating Characteristic (ROC) analysis showed the Area under the Curve (AUC) for the 6 variables ranged from 0.69 to 0.839. Multivariate k-means clustering analysis showed that Ponte/2 + PSO/3, BDBO/4 + SVCR/5, and MVCR/6 were three comparatively significant clusters, which could be discriminated by pre-operative kyphosis, T-DAR, age and S-DAR. CONCLUSION: This study showed that osteotomy plan of severe spinal deformity could be determined as follows: Firstly, Ponte/2 + PSO/3 and BDBO/4 + SVCR/5 + MVCR/6 groups can be divided by either T-DAR (cutoff = 28) or the Cobb angle of pre-operative maximum kyphosis (cutoff = 100). Secondly, Ponte/2 + PSO/3 group could be further dichotomized into Ponte/2 and PSO/3 by age (cutoff = 18). Finally, BDBO/4 + SVCR/5 + MVCR/6 group could be divided into BDBO/4 + SVCR/5 and MVCR/6 groups by S-DAR (cutoff = 20).

The radiographic, pulmonary, and clinical outcomes of patients with severe rigid spinal deformities treated via halo-pelvic traction.

BACKGROUND: The severe rigid deformity patients with pulmonary dysfunction could not tolerate complicated corrective surgery. Preoperative traction are used to reduce the curve magnitude and improve the pulmonary function before surgery, including halo-gravity traction (HGT) and halo-pelvic traction (HPT). The present study aimed to retrospectively compare the radiographic, pulmonary and clinical outcomes of preoperative HGT and HPT in severe rigid spinal deformity with respiratory dysfunction. METHODS: 81 cases of severe rigid kyphoscoliosis treated with preoperative traction prior to corrective surgery for spinal deformity between 2016 and 2019 were retrospectively reviewed. Two patient groups were compared, HPT group (N = 30) and HGT group (N = 51). Patient demographics, coronal and sagittal Cobb angles and correction rates, pulmonary function, traction time, osteotomy grade, and postoperative neurological complications were recorded for all cases. RESULTS: The coronal Cobb angle was corrected from 140.67 ± 2.63 to a mean of 120.17 ± 2.93° in the HGT group, and from 132.32 ± 4.96 to 87.59 ± 3.01° in the HPT group (mean corrections 15.33 ± 1.53 vs. 34.86 ± 3.11 %) (P = 0.001). The mean major sagittal curve decreased from 134.28 ± 3.77 to 113.03 ± 4.57° in the HGT group and from 129.60 ± 8.45 to 65.61 ± 7.86° in the HPT group (P < 0.001); the mean percentage corrections were 16.50 ± 2.13 and 44.09 ± 9.78 % (P < 0.001). A significant difference in the pulmonary function test results was apparent between the two groups; the mean improvements in the FVC% of the HGT and HPT groups were 6.76 ± 1.85 and 15.6 ± 3.47 % (P = 0.024). The HPT group tended to exhibit more FEV% improvement than the HGT group, but the difference was not significant (5.15 ± 2.27 vs. 11.76 ± 2.22 %, P = 0.91). CONCLUSIONS: Patients with severe rigid kyphoscoliosis who underwent preoperative HPT exhibited better radiographic correction of the deformity, and pulmonary function, and required fewer osteotomies compared to the HGT group. Thus, HPT may be useful for severe rigid spinal deformity patients with pulmonary dysfunction.

Transcriptomic analysis reveals resistance mechanisms of Klebsiella michiganensis to copper toxicity under acidic conditions.

The aim of this study was to elucidate the effect of pH on bacterial resistance mechanisms to copper (Cu) stress by genomic and transcriptomic analysis. Klebsiella michiganensis cells were exposed to 0.5 mM CuCl2 at pH 4 and 5. Lower pH (pH < 4) strongly inhibited K. michiganensis growth, while Cu stress and higher pH (pH > 5) induced Cu precipitation in the medium. Transcriptomic analyses indicated that two groups of genes related to quorum sensing (QS) systems (lsrABCDFGKR) and type II secretion systems (T2SS) (gspCDEFGHIJKLM) were significantly up-regulated at pH 4 only. These results suggest that T2SS may be induced and controlled by QS, thereby contributing to the formation of extracellular polymeric substances (EPS) and the secretion of proteins to prevent Cu ions from entering cells. Six Cu resistance genes (cusABF, copA, cueO, and gene05308) were more significantly up-regulated at pH 4 than at pH 5. In addition, the relative expression (log2|FC=) of the sulfur assimilation genes cysHJIK was relatively higher at pH 4 than at pH 5, while the gene encoding organic sulfur metabolism, tauB, was also significantly up-regulated at only pH 4. These results indicate that the Cu efflux system can remove intracellular Cu ions from cells, and that the sulfur assimilation system is related to the detoxification of Cu ions. Furthermore, increased free Cu ions at lower pH (4) could induce communication signals among cells, thereby stimulating the response of T2SS-related genes in K. michiganensis to tolerate Cu stress. Consequently, the resistance of K. michiganensis to Cu stress is a multisystem collaborative process composed of intracellular and extracellular components.

Stage-specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord.

Elucidation of signaling pathways that control oligodendrocyte (OL) development is a prerequisite for developing novel strategies for myelin repair in neurological diseases. Despite the extensive work outlining the importance of Hedgehog (Hh) signaling in the commitment and generation of OL progenitor cells (OPCs), there are conflicting reports on the role of Hh signaling in regulating OL differentiation and maturation. In the present study, we systematically investigated OPC specification and differentiation in genetically modified mouse models of Smoothened (Smo), an essential component of the Hh signaling pathway in vertebrates. Through conditional gain-of-function strategy, we demonstrated that hyperactivation of Smo in neural progenitors induced transient ectopic OPC generation and precocious OL differentiation accompanied by the co-induction of Olig2 and Nkx2.2. After the commitment of OL lineage, Smo activity is not required for OL differentiation, and sustained expression of Smo in OPCs stimulated cell proliferation but inhibited terminal differentiation. These findings have uncovered the stage-specific regulation of OL development by Smo-mediated Hh signaling, providing novel insights into the molecular regulation of OL differentiation and myelin repair.

Immune-related prognosis biomarkers associated with osteosarcoma microenvironment.

BACKGROUND: Osteosarcoma is a highly aggressive bone tumor that most commonly affects children and adolescents. Treatment and outcomes for osteosarcoma have remained unchanged over the past 30 years. The relationship between osteosarcoma and the immune microenvironment may represent a key to its undoing. METHODS: We calculated the immune and stromal scores of osteosarcoma cases from the Target database using the ESTIMATE algorithm. Then we used the CIBERSORT algorithm to explore the tumor microenvironment and analyze immune infiltration of osteosarcoma. Differentially expressed genes (DEGs) were identified based on immune scores and stromal scores. Search Tool for the Retrieval of Interacting Genes Database (STRING) was utilized to assess protein-protein interaction (PPI) information, and Molecular Complex Detection (MCODE) plugin was used to screen hub modules of PPI network in Cytoscape. The prognostic value of the gene signature was validated in an independent GSE39058 cohort. Gene set enrichment analysis (GSEA) was performed to study the hub genes in signaling pathways. RESULTS: From 83 samples of osteosarcoma obtained from the Target dataset, 137 DEGs were identified, including 134 upregulated genes and three downregulated genes. Functional enrichment analysis and PPI networks demonstrated that these genes were mainly involved in neutrophil degranulation and neutrophil activation involved in immune response, and participated in neuroactive ligand-receptor interaction and staphylococcus aureus infection. CONCLUSIONS: Our study established an immune-related gene signature to predict outcomes of osteosarcoma, which may be important targets for individual treatment.

Risk factors for neurological complications in severe and rigid spinal deformity correction of 177 cases.

BACKGROUND: Difficult procedures of severe rigid spinal deformity increase the risk of intraoperative neurological injury. Here, we aimed to investigate the preoperative and intraoperative risk factors for postoperative neurological complications when treating severe rigid spinal deformity. METHODS: One hundred seventy-seven consecutive patients who underwent severe rigid spinal deformity correction were assigned into 2 groups: the neurological complication (NC, 22 cases) group or non-NC group (155 cases). The baseline demographics, preoperative spinal cord functional classification, radiographic parameters (curve type, curve magnitude, and coronal/sagittal/total deformity angular ratio [C/S/T-DAR]), and surgical variables (correction rate, osteotomy type, location, shortening distance of the osteotomy gap, and anterior column support) were analyzed to determine the risk factors for postoperative neurological complications. RESULTS: Fifty-eight patients (32.8%) had intraoperative evoked potentials (EP) events. Twenty-two cases (12.4%) developed postoperative neurological complications. Age and etiology were closely related to postoperative neurological complications. The spinal cord functional classification analysis showed a lower proportion of type A, and a higher proportion of type C in the NC group. The NC group had a larger preoperative scoliosis angle, kyphosis angle, S-DAR, T-DAR, and kyphosis correction rate than the non-NC group. The results showed that the NC group tended to undergo high-grade osteotomy. No significant differences were observed in shortening distance or anterior column support of the osteotomy area between the two groups. CONCLUSIONS: Postoperative neurological complications were closely related to preoperative age, etiology, severity of deformity, angulation rate, spinal cord function classification, intraoperative osteotomy site, osteotomy type, and kyphosis correction rate. Identification of these risk factors and relative development of surgical techniques will help to minimize neural injuries and manage postoperative neurological complications.

Fiber Type-Specific Morphological and Cellular Changes of Paraspinal Muscles in Patients with Severe Adolescent Idiopathic Scoliosis.

BACKGROUND Paraspinal muscle (PSM) has been suggested to have a role in adolescent idiopathic scoliosis (AIS). Few studies have investigated the fiber type-specific changes of PSM in detail. MATERIAL AND METHODS Bilateral multifidus muscles were harvested from the apical vertebra level (T7-T10) of 12 AIS patients and 6 control individuals. Immunohistological staining was performed to evaluate the muscle fiber type composition, fiber type-specific cross-sectional area (CSA), myonuclei density, and the total and activated satellite cell (SC) density. The correlations between these characteristics and curve initiation/severity were analyzed. RESULTS In comparison with the PSM in convexity and the control group, PSM in concavity showed a significant reduction of CSA (concavity, 2601.1±574.1 µm²; convexity, 3732.1±545.1 µm²; control, 3426.5±248.4 µm²), myonuclei density (concavity, 2.0±0.3 myonuclei/fiber; convexity, 2.5±0.4 myonuclei/fiber; control, 2.2±0.2 myonuclei/fiber), and activated SC density (concavity, 0.7±0.4 cells/100 fibers; convexity, 1.5±0.7 cells/100 fibers; control, 1.2±0.3 cells/100 fibers) for fiber type I. The Cobb angle was positively correlated with the bilateral ratio of CSA (convexity/concavity) for both fiber types. The apical vertebral translation was positively correlated with bilateral difference of myonuclei density (type I), total SC density (types I and II), and activated SC density (type I). CONCLUSIONS The fiber type-specific pathological changes on the concave side seemed to be more severe. Some fiber type-specific characteristics (CSA, myonuclei density, total/activated SC density) were closely associated with curve severity. More attention should be paid to PSM physiotherapy treatment on the concave side.

A Retrospective Study of Surgical Correction for Spinal Deformity with and without Osteotomy to Compare Outcome Using Intraoperative Neurophysiological Monitoring with Evoked Potentials.

BACKGROUND This study aimed to evaluate the effects of different combined evoked potentials monitoring modes for non-osteotomy and osteotomy surgery of spinal deformity, and to select individualized modes for various surgeries. MATERIAL AND METHODS We retrospectively reviewed a total of 188 consecutive cases undergoing spinal deformity correction. All patients were classified into 2 cohorts: non-osteotomy (Group A) and osteotomy (Group B). According to intraoperative evoked potential monitoring mode, Group A was divided into 2 sub-groups: A1 [spinal somatosensory evoked potential (SSEP)/motor evoked potential (MEP), n=67)] and A2 [SSEP/MEP/descending neurogenic evoked potential (DNEP), n=52]. Group B was classified as B1 (SSEP/MEP, n=27) and B2 (SSEP/MEP/DNEP, n=42). The demographics, surgical parameters, and evoked potential events of different combined monitoring modes were analyzed within each group. RESULTS The baselines of SSEP/MEP/DNEP in all cases were elicited successfully. Three cases with evoked potential (EP) events (2 with MEP changes and 1 with SSEP/MEP change) were noted in Group A1 and 1 with SSEP change in Group A2, with no neurological complications. Thirteen cases in Group B1 were positive for MEP intraoperatively, including 16 EP events (13 with MEP change and 3 with both SSEP+MEP changes), with no neural complications. In Group B2, 15 cases had 21 EP events, including 12 with MEP change and 2 with SSEP+MEP changes, with no complications. Postoperative neurological complications were observed in 5 of the 7 cases with SS4EP/DNEP changes. CONCLUSIONS Intraoperative simultaneous SSEP/MEP can effectively reflect neurological function in non-osteotomy spinal surgery patients. Simultaneous SSEP/MEP/DNEP can effectively avoid the unnecessary interference by false-positive results of MEP during osteotomy.

Molecular and Genetic Evidence for the PDGFRα-Independent Population of Oligodendrocyte Progenitor Cells in the Developing Mouse Brain.

PDGFRα, specifically expressed by immature oligodendrocyte progenitor cells (OPCs) in the CNS, plays a critical role in OPC proliferation and migration. However, it has been uncertain whether all cells of oligodendrocyte lineage are derived from the PDGFRα-expressing OPCs. In the present study, we uncovered a PDGFRα-independent oligodendrocyte lineage in the developing cortex. This OPC subpopulation originates from the local ventricular/subventricular zone after birth and contributes to the earliest mature oligodendrocytes in the cortex. PDGFRα signaling does not regulate the generation and differentiation of cortical OPCs. Fate-mapping studies in the PDGFRαCreER; Sox10-GFP/tdTom double-transgenic mice of either sex have further corroborated the PDGFRα-independent oligodendrocyte lineage. This study provides additional missing genetic evidence for PDGFRα-independent oligodendrocyte lineage in the developing hindbrain.SIGNIFICANCE STATEMENT This is the first report of a subpopulation of oligodendrocyte lineage in the developing mouse cortex independent of PDGFRα signaling. These oligodendrocyte progenitor cells are generated from the local ventral ventricular zone/subventricular zone after birth, and contribute to the earliest mature oligodendrocytes in the cortex.

Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection.

Aortic dissection (AD) is the circumferential or transversal tear of the aorta wall that allows blood to infiltrate the layers. MicroRNA (miR) analyses have demonstrated a correlation between miR-320 family and AD. The underlying mechanism is yet unclear. The matrix metalloproteinases (MMPs) are a group of proteolytic enzymes that could catalyze the degeneration of the extracellular matrix and the destruction of the vasculature. In this study, we investigated whether miR-320 presented a role in regulating the production of MMPs in aortic dissection. In a cohort of 30 CE patients and 30 healthy controls, the transcription and secretion of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12 by monocytes were investigated. The monocyte from AD patients presented significantly elevated capacity of MMP expression than those from healthy controls. In contrast, the monocyte/macrophage expression of miR-320 was significantly lower in AD patients than in controls. In both AD patients and healthy controls, LPS-activation of macrophages resulted in MMP upregulation and miR-320 downregulation, in which the MMP expression was significantly higher while the miR-320 expression was significantly lower in AD patients than in healthy controls. Transfection of miR-320 mimic did not affect MMP gene transcription but significantly reduced the protein production in some MMPs, demonstrated that miR-320 were involved in the post-transcriptional regulation of MMPs. Together, these results demonstrated that miR-320 could regulate the expression of MMPs by macrophages, through which miR-320 may interfere with AD development.