Nomogram for predicting venous thromboembolism after spinal surgery.

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

Identification of inducible CYP3 and CYP4 genes associated with abamectin tolerance in the fat body and Malpighian tubules of Spodoptera litura.

Abamectin, as a broad-spectrum bioinsecticide, has been widely used for the control of Lepidoptera insects, resulting in different levels of resistance to abamectin in Spodoptera litura. Cytochrome P450 monooxygenases (P450s) are known for their important roles in insecticide detoxification. In this study, the expression of SlCYP6B40, SlCYP4L12 and SlCYP9A32 in the fat body, and SlCYP4S9, SlCYP6AB12, SlCYP6AB58, SlCYP9A75a and SlCYP9A75b in Malpighian tubules was found to be significantly upregulated after abamectin exposure. SlCYP6AE44 and SlCYP6AN4 were simultaneously upregulated in these two tissues after abamectin exposure. Ectopically overexpressed SlCYP6AE44, SlCYP9A32 and SlCYP4S9 in transgenic Drosophila conferred tolerance to abamectin. In addition, homology modeling and molecular docking results suggested that SlCYP6AE44, SlCYP9A32 and SlCYP4S9 may be capable of binding with abamectin. These results demonstrate that upregulation of CYP3 and CYP4 genes may contribute to abamectin detoxification in S. litura and provide information for evidence-based insecticide resistance management strategies.

ATRX loss induces telomere dysfunction and necessitates induction of alternative lengthening of telomeres during human cell immortalization.

Loss of the histone H3.3-specific chaperone component ATRX or its partner DAXX frequently occurs in human cancers that employ alternative lengthening of telomeres (ALT) for chromosomal end protection, yet the underlying mechanism remains unclear. Here, we report that ATRX/DAXX does not serve as an immediate repressive switch for ALT. Instead, ATRX or DAXX depletion gradually induces telomere DNA replication dysfunction that activates not only homology-directed DNA repair responses but also cell cycle checkpoint control. Mechanistically, we demonstrate that this process is contingent on ATRX/DAXX histone chaperone function, independently of telomere length. Combined ATAC-seq and telomere chromatin immunoprecipitation studies reveal that ATRX loss provokes progressive telomere decondensation that culminates in the inception of persistent telomere replication dysfunction. We further show that endogenous telomerase activity cannot overcome telomere dysfunction induced by ATRX loss, leaving telomere repair-based ALT as the only viable mechanism for telomere maintenance during immortalization. Together, these findings implicate ALT activation as an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction.

CeO2 Promotes CO2 Electroreduction to Formate on Bi2S3 via Tuning of the *OCHO Intermediate.

Formate is identified as economically viable chemical fuel from electrochemical carbon dioxide reduction. However, the selectivity of current catalysts toward formate is limited by the competitive reaction such as HER. Herein, we propose a CeO2 modification strategy to improve the selectivity of catalysts for formate through tuning of the *OCHO intermediate, which is important for formate production.

Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes. METHODS: The records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing. RESULTS: Twenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid. CONCLUSIONS: NPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Endoscopic submucosal dissection training: evaluation of an ex vivo training model with continuous perfusion (ETM-CP) for hands-on teaching and training in China.

BACKGROUND: The existing ex vivo models of endoscopic submucosal dissection (ESD) cannot simulate intraoperative hemorrhage well. We aimed to establish an ESD training method by applying an ex vivo training model with continuous perfusion (ETM-CP). METHODS: Four training sessions were conducted for 25 novices under the guidance of 2 experts. Eventually, 10 novices completed ESD operations on a total of 89 patients after the training. The resection effectiveness, resection speed, complication rate, and novice performance before and after the training were compared. The data regarding the effects of the training and the model were gathered through a questionnaire survey. RESULTS: In terms of the simulation effect of the model, ETM-CP was evaluated as similar to the live pig in all aspects (P > 0.05). The questionnaire analysis revealed that the ESD theoretical knowledge, skill operation, and self-confidence of novices were improved after the training (P < 0.05). The resection time per unit area had a correlation with the number of training periods (rs = - 0.232). For novice performance, the resection time per unit area was shortened (P < 0.05). There was no difference in patient performance between the novice group and the expert group after the training in terms of en bloc resection, R0 resection, complication rate, endoscopic resection bleeding (ERB) score, muscularis propria injury (MPI) score, and resection time per unit area (P > 0.05). CONCLUSION: The ETM-CP is effective for ESD training.

Genomic Identification of CCCH-Type Zinc Finger Protein Genes Reveals the Role of HuTZF3 in Tolerance of Heat and Salt Stress of Pitaya (Hylocereus polyrhizus).

Pitaya (Hylocereus polyrhizus) is cultivated in a broad ecological range, due to its tolerance to drought, heat, and poor soil. The zinc finger proteins regulate gene expression at the transcriptional and post-transcriptional levels, by interacting with DNA, RNA, and proteins, to play roles in plant growth and development, and stress response. Here, a total of 81 CCCH-type zinc finger protein genes were identified from the pitaya genome. Transcriptomic analysis showed that nine of them, including HuTZF3, responded to both salt and heat stress. RT-qPCR results showed that HuTZF3 is expressed in all tested organs of pitaya, with a high level in the roots and stems, and confirmed that expression of HuTZF3 is induced by salt and heat stress. Subcellular localization showed that HuTZF3 is targeted in the processing bodies (PBs) and stress granules (SGs). Heterologous expression of HuTZF3 could improve both salt and heat tolerance in Arabidopsis, reduce oxidative stress, and improve the activity of catalase and peroxidase. Therefore, HuTZF3 may be involved in post-transcriptional regulation via localizing to PBs and SGs, contributing to both salt and heat tolerance in pitaya.

Activated Ni-O-Ir Enhanced Electron Transfer for Boosting Oxygen Evolution Reaction Activity of LaNi1-x Irx O3.

Tuning the structure of the active center of catalysts to atomic level provides the most efficient utilization of the active component, which plays an especially important role for precious metals. In this study, the liquid phase ion exchange method is used to introduce atomic Ir into LaNiO3 perovskite oxide, which shows excellent catalytic performance in the oxygen evolution reaction (OER). The catalyst, LaNi0.96 Ir0.04 O3 , with the optimal concentration of Ir, displays an overpotential of just 280 mV at 10 mA cm-2 . The introduced Ir enriches the surface electron density significantly, which not only improves site-to-site electron transfer between O and Ni sites but also allows stable adsorption of the intermediates. The results of cyclic voltammetry tests reveal the superior overpotential and remarkable efficiency of the OER process because of the strong interactions in Ni-O-Ir. Moreover, the Ir atom inhibits the participation of a lattice oxygen oxidation mechanism (LOM) in LaNiO3 that guarantees the stability of the catalyst in alkaline conditions. It is anticipated that this work will be instrumental for the preparation and study of a broad range of atomic metal-doped perovskite oxides for water splitting.

Clinical benefit of tunnel endoscopic submucosal dissection for esophageal squamous cancer: a multicenter, randomized controlled trial.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is widely accepted as a primary treatment modality for dysplastic and early cancerous lesions of the GI tract. However, prolonged procedure time and life-threatening adverse events remain obstacles to the successful treatment of esophageal cancer. This study aimed to compare the efficacy and safety of tunnel ESD (T-ESD) with conventional ESD (C-ESD) for superficial esophageal squamous neoplasms. METHODS: A prospective, multicenter trial was conducted at 5 hospitals in China. Patients with esophageal squamous neoplasms were enrolled and randomly assigned to undergo C-ESD or T-ESD. Randomization was stratified by tumor location and circumference extent (<1/2 or ≥1/2). The primary endpoint was procedure time. RESULTS: Between January and July 2018, 160 patients were enrolled. One hundred fifty-two patients (76 in the C-ESD group and 76 in the T-ESD group) were included in the final analysis. The median procedure time was 47.3 minutes (interquartile range, 31.7-81.3) for C-ESD and 40.0 minutes (interquartile range, 30.0-60.0) for T-ESD (P = .095). However, T-ESD specifically reduced the median procedure time 34.5% (29.5 minutes) compared with C-ESD for lesions ≥1/2 circumference (P < .001). Among the multiple secondary outcomes, muscular injury was less frequent in the T-ESD group compared with the C-ESD group (18.4% vs 38.2%, P = .007), but complete healing of artificial mucosal defect in 1-month follow-up was more common in the T-ESD group than the C-ESD group (95.9% vs 84.7%, P =.026). CONCLUSIONS: Our study suggests that T-ESD results in shorter procedure time, specifically for lesions ≥1/2 circumference of the esophagus. In addition, T-ESD has a better safety profile indicated by less frequent muscular injury and improved healing of artificial mucosal defects caused by ESD procedures. (Clinical trial registration number: NCT03404921.).

Management of a multiple endocrine neoplasia type 1 during pregnancy: a case with primary hypertension.

Multiple endocrine neoplasia type 1 (MEN 1) is a rare hereditary disease which transmitted as autosomal dominant disorder with high penetrance. MEN1 includes vary combinations of more than 20 endocrine and non-endocrine tumors. Clinically, MEN1 is characterized by tumor or hyperplasia in two or more endocrine tissues (parathyroid, pituitary, pancreas, adrenal glands). Since it is a rare condition, there are no guidelines with respect to the follow-up of pregnant women with MEN 1, here we the first Asian case of a 32-year-old primigravida with a confirmed diagnosis of MEN1 and primary hypertension prior to conception, cesarean section was performed at 34+2 weeks for severe preeclampsia and potential risks, both the patient and fetus recovered well.

Antibiotic-loaded calcium sulfate beads in spinal surgery for patients with spondylodiscitis: a clinical retrospective study.

BACKGROUND: Various surgical techniques for treating spondylodiscitis have been proposed, but the optimal surgical treatment remains controversial. In this study, we propose a new procedure that is implanting antibiotic-loaded calcium sulfate (CS) beads into the disc after debridement using the Quadrant channel combined with percutaneous fixation through a single-stage posterolateral approach for the treatment of spondylodiscitis. Thus, the purpose of this study is to assess the safety and efficacy of this procedure. METHODS: This study collected the data of 32 patients with spine spondylodiscitis and was surgically treated in our department from July 2015 to August 2020. The Demographic data included age, gender, involved segment, and complications were collected. The intra-operative details, results of culture, functional outcome, radiologic outcome, and length of hospital stay, laboratory examination were recorded. RESULTS: The mean age of the 32 patients was 61.1 ± 9.7 years old. The mean operative time was 135.0 ± 30.6 minutes, and the mean blood loss was 243.4 ± 92.1 ml. The positive rate of culture was 72%. The mean Visual analogue scale (VAS) and Oswestry Disability Index (ODI) score significantly improved from 7.5 to 1.6 and from 65% to 10%. Cobb angle was significantly improved and could be maintained at final follow-up. New bone formation was observed in all patients. There were no recurrences of infection in our study. CONCLUSIONS: The posterolateral debridement and percutaneous fixation combined with antibiotic-loaded calcium sulfate beads filling are effective in the treatment of spondylodiscitis in terms of infection control, early mobilization, and recovery.

Chemosensory proteins confer adaptation to the ryanoid anthranilic diamide insecticide cyantraniliprole in Aphis gossypii glover.

Chemosensory proteins (CSPs) are a class of small transporter proteins expressed only in arthropods with various functions beyond chemoreception. Previous studies have been reported that CSPs are involved in the insecticide resistance. In this study, we found that AgoCSP1, AgoCSP4, and AgoCSP5 were constitutively overexpressed in an insecticide-resistant strain of Aphis gossypii and showed higher expression in broad body tissue (including fat bodies) than in the midgut but without tissue specificity. However, the function of these three upregulated AgoCSPs remains unknown. Here, we investigated the function of AgoCSPs in resistance to the diamide insecticide cyantraniliprole. Suppression of AgoCSP1, AgoCSP4 and AgoCSP5 transcription by RNAi significantly increased the sensitivity of resistant aphids to cyantraniliprole. Molecular docking and competitive binding assays indicated that these AgoCSPs bind moderate with cyantraniliprole. Transgenic Drosophila melanogaster expressing these AgoCSPs in the broad body or midgut showed higher tolerance to cyantraniliprole than control flies with the same genetic background; AgoCSP4 was more effective in broad body tissue, and AgoCSP1 and AgoCSP5 were more effective in the midgut, indicating that broad body and midgut tissues may be involved in the insecticide resistance mediated by the AgoCSPs examined. The present results strongly indicate that AgoCSPs participate in xenobiotic detoxification by sequestering and masking toxic insecticide molecules, providing insights into new factors involved in resistance development in A. gossypii.

Functional analysis of cyantraniliprole tolerance ability mediated by ATP-binding cassette transporters in Aphis gossypii glover.

Cyantraniliprole, a second-generation anthranilic diamide insecticide, is widely used to control chewing and sucking pests. ATP-binding cassette transporters (ABCs) are a ubiquitous family of membrane proteins that play important roles in insect detoxification mechanisms. However, the potential effects of ABCs on cyantraniliprole-resistance remain unclear. In the present study, synergism bioassays revealed that verapamil, an ABC inhibitor, increased the toxicity of cyantraniliprole by 2.00- and 12.25-fold in the susceptible and cyantraniliprole-resistant strains of Aphis gossypii. Based on transcriptome data, the expression levels of ABCB4, ABCB5, ABCD1, ABCG4, ABCG7, ABCG13, ABCG16, ABCG17, ABCG26 and MRP12 were upregulated 1.56-, 1.32-, 1.51-, 2.03-, 1.65-, 1.50-, 4.18-, 6.07-, 4.68- and 4.69-fold, respectively, in the cyantraniliprole-resistant strain (CyR) compared to the susceptible strain (SS), as determined using RT-qPCR. Drosophila melanogaster ectopically overexpressing ABCB5, ABCG4, ABCG7, ABCG16, ABCG17, ABCG26 and MRP12 exhibited significantly increased tolerance to cyantraniliprole by 11.71-, 2.39-, 4.85-, 2.06-, 3.75-, 4.20- and 3.50-fold, respectively, with ABCB5 and ABCG family members being the most effective. Furthermore, the suppression of ABCB5, ABCG4, ABCG7, ABCG16, ABCG17, ABCG26 and MRP12 significantly increased the sensitivity of the CyR strain to cyantraniliprole. These results indicate that ABCs may play crucial roles in cyantraniliprole resistance and may provide information for shaping resistance management strategies.

Functional characterization of ABC transporters mediates multiple neonicotinoid resistance in a field population of Aphis gossypii Glover.

The ATP-binding cassette (ABC) transporters C and G subfamilies have been reported to be involved in insecticide detoxification, with most studies showing increased gene transcript levels in response to insecticide exposure. Our previous studies have suggested that ABCC and G transporters participate in cyantraniliprole and thiamethoxam resistance of Aphis gossypii. In this study, we focused on the potential roles of the ABCC and G transporters of an A. gossypii field population (SDR) in neonicotinoid detoxification. The results of leaf dip bioassays showed 629.17- and 346.82-fold greater resistance to thiamethoxam and imidacloprid in the SDR strain, respectively, than in the susceptible strain (SS). Verapamil, an ABC inhibitor, was used for synergism bioassays, and the results showed synergistic effects with thiamethoxam, with synergistic ratios (SRs) of 2.07 and 6.68 in the SS and SDR strains, respectively. In addition to thiamethoxam, verapamil increased imidacloprid toxicity by 1.68- and 1.62-fold in the SS and SDR strains respectively. Then, the expression levels of several ABCC and G transporters were analyzed in different treatments. We found that the transcript levels of AgABCG4, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 were higher in the SDR strain than in the SS strain. The mRNA expression of AgABCG4, AgABCG7, AgABCG13, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 in the SDR strain was increased after thiamethoxam and imidacloprid exposure. The results of transgenic Drosophila melanogaster bioassays suggested that overexpression of AgABCG4, AgABCG7, AgABCG13, AgABCG17, AgABCG26, AgMRP8 and AgMRP12 in transgenic flies was sufficient to confer thiamethoxam and imidacloprid resistance, and AgABCG4, AgABCG7, AgABCG13, AgABCG26 and AgMRP12 may be related to α-cypermethrin cross-resistance with weak effects. In addition, the knockdown of AgABCG4, AgABCG13, AgABCG26, AgMRP8 and AgMRP12, and the knockdown of AgABCG7 and AgABCG26 increased thiamethoxam and imidacloprid mortality in the SDR strain, respectively. Our results suggest that changes in the expression levels of ABCC and G transporters may contribute to neonicotinoid detoxification in the SDR strain, and provide a foundation for clarify the potential roles of ABCC and G transporters in insecticide resistance.

Chemosensory Proteins Are Associated with Thiamethoxam and Spirotetramat Tolerance in Aphis gossypii Glover.

Chemosensory proteins (CSPs) are a class of transporters in arthropods. Deeper research on CSPs showed that CSPs may be involved in some physiological processes beyond chemoreception, such as insect resistance to pesticides. We identified two upregulated CSPs in two resistant strains of Aphis gossypii Glover. To understand their role in the resistance of aphids to pesticides, we performed the functional verification of CSP1 and CSP4 in vivo and in vitro. Results showed that the sensitivity of the thiamethoxam-resistant strain to thiamethoxam increased significantly with the silencing of CSP1 and CSP4 by RNAi (RNA interference), and the sensitivity of the spirotetramat-resistant strain to spirotetramat increased significantly with the silencing of CSP4. Transgenic Drosophila melanogaster expressing CSPs exhibited stronger resistance to thiamethoxam, spirotetramat, and alpha-cypermethrin than the control did. In the bioassay of transgenic Drosophila, CSPs showed different tolerance mechanisms for different pesticides, and the overexpressed CSPs may play a role in processes other than resistance to pesticides. In brief, the present results prove that CSPs are related to the resistance of cotton aphids to insecticides.

Current status of cancer starvation therapy.

Conventional therapies for malignant tumors have limitations and disadvantages. In recent years, the cancer starvation therapy has emerged which intends to deprive cancer cells of nutritional supply. There are several approaches to"starve" cancer cells: to intervene tumor angiogenesis by targeted inhibition of angiogenic factors or their receptors and integrins; to block the blood supply of cancer cells by embolizing or compressing blood vessels; to intervene metabolic process of cancer cells by inhibition of the signal pathways of mitochondrial serine-glycine-one earbon metabolism, glycolysis and amino acid metabolism; cancer starvation therapy can be employed with oxidation therapy, chemotherapy, sonodynamic therapy, anti-autophagy therapy or other therapies to achieve synergistic effects. This article reviews the research progress of cancer starvation therapy in recent years and discusses the existing problems.

Surface Activation and Ni-S Stabilization in NiO/NiS2 for Efficient Oxygen Evolution Reaction.

Manipulating the active species and improving the structural stabilization of sulfur-containing catalysts during the OER process remain a tremendous challenge. Herein, we constructed NiO/NiS2 and Fe-NiO/NiS2 as catalyst models to study the effect of Fe doping. As expected, Fe-NiO/NiS2 exhibits a low overpotential of 270 mV at 10 mA cm-2 . The accumulation of hydroxyl groups on the surface of materials after Fe doping can promote the formation of highly active NiOOH at a lower OER potential. Moreover, we investigated the level of corrosion of M-S bonds and compared the stability variation of M-S bonds with Fe at different locations. Interestingly, Fe bonded with S in the bulk as the sacrificial agent can alleviate the oxidation corrosion of partial Ni-S bonds and thus endow Fe-NiO/NiS2 long-term durability. This work could motivate the community to focus more on resolving the corrosion of sulfur-containing materials.

Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients.

BACKGROUND: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. METHODS: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. RESULTS: In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. CONCLUSION: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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).

Functional validation of key cytochrome P450 monooxygenase and UDP-glycosyltransferase genes conferring cyantraniliprole resistance in Aphis gossypii Glover.

Cytochrome P450 monooxygenases (P450s) and UDP-glycosyltransferases (UGTs) are major detoxifying enzymes that metabolize plant toxins and insecticides. In the present study, the synergists of piperonyl butoxide, sulfinpyrazone and 5-nitrouracil significantly increased cyantraniliprole and α-cypermethrin toxicity against the resistant strain. The transcripts of UGT341A4, UGT344B4, UGT344D6, UGT344J2 and UGT344M2 increased significantly in the CyR strain compared with the susceptible strain. Among these upregulated genes (including P450s), CYP6CY7 and UGT344B4 were highly expressed in the midgut. Transgenic expression of the P450 and UGT genes in broad body tissues in Drosophila melanogaster indicated that the expression of CYP380C6, CYP4CJ1, UGT341A4, UGT344B4 and UGT344M2 is sufficient to confer cyantraniliprole resistance, and CYP380C6, CYP6CY7, CYP6CY21, UGT341A4 and UGT344M2 are related to α-cypermethrin cross-resistance. The midgut-specific overexpression of CYP380C6, CYP6CY7, CYP6CY21, CYP4CJ1, UGT341A4, UGT344B4 and UGT344M2 significantly increased insensitivity to cyantraniliprole, and CYP380C6, CYP6CY7, CYP6CY21, UGT344B4 and UGT344M2 confer α-cypermethrin cross-resistance. The expression of CYP380C6, CYP4CJ1, UGT341A4 and UGT344M2 in broad tissues or in midgut has similar effects on insensitivity to insecticides; however, CYP6CY7, CYP6CY21 and UGT344B4 are more effective in the midgut. This result indicates that broad body tissues and midgut tissue are involved in insecticide resistance mediated by the candidate P450s and UGTs examined.