Search

Background: Acute hepatic dysfunction (AHD) is a common postoperative complication in patients with acute type A aortic dissection. The aim of this study was to identify risk factors for acute hepatic dysfunction after surgery for acute type A aortic dissection., Methods: We performed a retrospective study from March 1, 2019, to February 28, 2021. The primary endpoints of this study were morbidity due to AHD and risk factors for incidence. Univariate analysis and multivariate logistic regression analysis were used to analyse the related factors, and receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value., Results: Among 147 patients, 29 (19.73%) developed postoperative acute hepatic dysfunction, and 9 (6.12%) died. Univariate analysis revealed that the ALT (P = 0.042), Cr (P < 0.001), and BUN (P = 0.008) levels were significantly different between the two groups. Multivariate logistic regression analysis revealed that Cr (OR = 1.013, 95% CI = 1.003-1.023, P = 0.008) was an independent risk factor for postoperative hepatic dysfunction in overweight (BMI > 24) patients with ATAAD. The area under the ROC curve (AUC) for Cr was 0.745 > 0.7, indicating good predictive value., Conclusion: A high Cr concentration is an independent risk factor for postoperative AHD in overweight (BMI > 24) patients with ATAAD., (© 2024. The Author(s).)

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis., Patients & Methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model., Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908)., Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yu, Zhang, Xu, Lin, Guo, Li, Huang and Huang.)

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Acute mesenteric vein thrombosis (AMVT) is an acute abdominal disease with onset, rapid progression, and extensive intestinal necrosis that requires immediate surgical resection. The purpose of this study was to determine the risk factors for nosocomial intestinal resection in patients with AMVT., Methods: We retrospectively analysed 64 patients with AMVT diagnosed by CTA at the Affiliated Hospital of Kunming University of Science and Technology from January 2013 to December 2021. We compared patients who underwent intestinal resection (42 patients) with those who did not undergo intestinal resection (22 patients). The area under the ROC curve was evaluated, and a forest map was drawn., Results: Among the 64 patients, 6 (9.38%) had a fever, 60 (93.75%) had abdominal pain, 9 (14.06%) had a history of diabetes, 8 (12.5%) had a history of deep vein thrombosis (DVT), and 25 (39.06%) had ascites suggested by B ultrasound or CT after admission. The mean age of all patients was 49.86 ± 16.25 years. The mean age of the patients in the enterectomy group was 47.71 ± 16.20 years. The mean age of the patients in the conservative treatment group (without enterectomy) was 53.95 ± 15.90 years. In the univariate analysis, there were statistically significant differences in leukocyte count (P = 0.003), neutrophil count (P = 0.001), AST (P = 0.048), total bilirubin (P = 0.047), fibrinogen (P = 0.022) and DD2 (P = 0.024) between the two groups. The multivariate logistic regression analysis showed that admission white blood cell count (OR = 1.153, 95% CI: 1.039-1.280, P = 0.007) was an independent risk factor for intestinal resection in patients with AMVT. The ROC curve showed that the white blood cell count (AUC = 0.759 95% CI: 0.620-0.897; P = 0.001; optimal threshold: 7.815; sensitivity: 0.881; specificity: 0.636) had good predictive value for emergency enterectomy for AMVT., Conclusions: Among patients with AMVT, patients with a higher white blood cell count at admission were more likely to have intestinal necrosis and require emergency enterectomy. This study is helpful for clinicians to accurately determine whether emergency intestinal resection is needed in patients with AMVT after admission, prevent further intestinal necrosis, and improve the prognosis of patients., (© 2024. The Author(s).)

Objective: To analyze the clinical characteristics of patients with overweight acute type A aortic dissection, and to explore the risk factors of acute kidney injury in patients with overweight acute type A aortic dissection., Methods: From March 2019 to February 2022, the clinical data of 71 patients with acute type a aortic dissection diagnosed by CTA and undergoing surgical treatment with BMI > 24 in the First People's Hospital of Yunnan Province were retrospectively analyzed, and analyzed by univariate and logistic multivariate analysis methods., Results: The mean BMI of all included patients was 27.23, The mean surface area of all included human populations was 1.833. The mean age of all patients was (52.06 ± 10.71) years old, and 35 patients developed acute kidney injury after surgery. Multi-factor Logistics regression analysis confirmed the risk factors for postoperative acute kidney injury in overweight patients with acute type A aortic dissection, including gender, CPB transit time and intraoperative infusion of suspended red blood cells. Seven patients in the AKI group died in hospital after surgery and two patients died in the non-AKI group., Conclusions: Among patients with overweight acute Type A aortic dissection, the incidence of AKI is 49.30%. According to multi-factor Logistics regression analysis, gender, CPB transit time and intraoperative suspended red blood cell volume are independent risk factors for postoperative acute kidney injury in patients with overweight acute Type A aortic dissection., (© 2023. The Author(s).)

Global biodiversity decline and its cascading effects through trophic interactions pose a severe threat to human society. Establishing the impacts of biodiversity decline requires a more thorough understanding of multi-trophic interactions and, more specifically, the effects that loss of diversity in primary producers has on multi-trophic community assembly. Within a synthetic conceptual framework for multi-trophic beta-diversity, we tested a series of hypotheses on neutral and niche-based bottom-up processes in assembling herbivore and carnivore communities in a subtropical forest using linear models, hieratical variance partitioning based on linear mixed-effects models (LMMs) and simulation. We found that the observed taxonomic, phylogenetic and functional beta-diversity of both herbivorous caterpillars and carnivorous spiders were significantly and positively related to tree dissimilarity. Linear models and variance partitioning for LMMs jointly suggested that as a result of bottom-up effects, producer dissimilarities were predominant in structuring consumer dissimilarity, the strength of which highly depended on the trophic dependencies on producers, the diversity facet examined, and data quality. Importantly, linear models for standardized beta-diversities against producer dissimilarities implied a transition between niche-based processes such as environmental filtering and competitive exclusion, which supports the role of bottom-up effect in determining consumer community assembly. These findings enrich our mechanistic understanding of the 'Diversity Begets Diversity' hypothesis and the complexity of higher-trophic community assembly, which is fundamental for sustainable biodiversity conservation and ecosystem management., (© 2022 The Authors. Journal of Animal Ecology © 2022 British Ecological Society.)

Human-induced biodiversity loss negatively affects ecosystem function, but the interactive effects of biodiversity change across trophic levels remain insufficiently understood. We sampled arboreal spiders and lepidopteran larvae across seasons in 2 years in a subtropical tree diversity experiment, and then disentangled the links between tree diversity and arthropod predator diversity by deconstructing the pathways among multiple components of diversity (taxonomic, phylogenetic and functional) with structural equation models. We found that herbivores were major mediators of plant species richness effects on abundance, species richness, functional and phylogenetic diversity of predators, while phylogenetic, functional and structural diversity of trees were also important mediators of this process. However, the strength and direction differed between functional, structural and phylogenetic diversity effects, indicating different underlying mechanisms for predator community assembly. Abundance and multiple diversity components of predators were consistently affected by tree functional diversity, indicating that the variation in structure and environment caused by plant functional composition might play key roles in predator community assembly. Our study highlights the importance of an integrated approach based on multiple biodiversity components in understanding the consequences of biodiversity loss in multitrophic communities.

Background: Endoplasmic reticulum (ER) stress plays a pro-apoptotic role in colorectal adenocarcinoma (COAD). This study aimed to develop a novel ER-stress-related prognostic risk model for COAD and provide support for COAD cohorts with different risk score responses to immune checkpoint inhibitor therapies. Methods: TCGA-COAD and GSE39582 were included in this prospective study. Univariate and multivariate Cox analyses were performed to identify prognostic ER stress-related genes (ERSGs). Accordingly, the immune infiltration landscape and immunotherapy response in different risk groups were assessed. Finally, the expression of prognostic genes in 10 normal and 10 COAD tissue samples was verified using reverse transcription-quantitative polymerase chain reaction. Results: Eight prognostic genes were selected to establish an ERSG-based signature in the training set of the TCGA-COAD cohort. The accuracy of this was confirmed using a testing set of TCGA-COAD and GSE39582 cohorts. Gene set variation analysis indicated that differential functionality in high-low-risk groups was related to immune-related pathways. Corresponding to this, CD36 , TIMP1 , and PTGIS were significantly associated with 19 immune cells with distinct proportions between the different risk groups, such as central memory CD4T cells and central memory CD8T cells. Moreover, the risk score was considered effective for predicting the clinical response to immunotherapy, and the immunotherapy response was significantly and negatively correlated with the risk score of individuals with COAD. Furthermore, the immune checkpoint inhibitor treatment was less effective in the high-risk group, where the expression levels of PD-L1 and tumor immune dysfunction and exclusion scores in the high-risk group were significantly increased. Finally, the experimental results demonstrated that the expression trends of prognostic genes in clinical samples were consistent with the results from public databases. Conclusion: Our study established a novel risk signature to predict the COAD prognosis of patients and provide theoretical support for the clinical treatment of COAD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Organosilicone molecules represent important components of surfactants added to pesticides to improve pest control efficiency, but these molecules also have pesticidal properties in their own right. Here, we examined toxicity and control efficacy of Silwet 408, a trisiloxane ethoxylate-based surfactant, to the two-spotted spider mite (TSSM), Tetranychus urticae and its crop hosts. Silwet 408 was toxic to nymphs and adults of TSSM but did not affect eggs. Field trials showed that the control efficacy of 1000 mg/L Silwet 408 aqueous solution reached 96% one day after spraying but declined to 54% 14 days after spraying, comparable to 100 mg/L cyetpyrafen, a novel acaricide. A second spraying of 1000 mg/L Silwet 408 maintained control efficacy at 97% when measured 14 days after spraying. However, Silwet 408 was phytotoxic to eggplant, kidney bean, cucumber, and strawberry plants, although phytotoxicity to strawberry plants was relatively low and declined further seven days after application. Our study showed that while the organosilicone surfactant Silwet 408 could be used to control the TSSM, its phytotoxicity to crops should be considered.

Clathrin-coated structures must assemble on cell membranes to internalize receptors, with the clathrin protein only linked to the membrane via adaptor proteins. These structures can grow surprisingly large, containing over 20 clathrin, yet they often fail to form productive vesicles, instead aborting and disassembling. We show that clathrin structures of this size can both form and disassemble spontaneously when adaptor protein availability is low, despite high abundance of clathrin. Here, we combine recent in vitro kinetic measurements with microscopic reaction-diffusion simulations and theory to differentiate mechanisms of stable vs unstable clathrin assembly on membranes. While in vitro conditions drive assembly of robust, stable lattices, we show that concentrations, geometry, and dimensional reduction in physiologic-like conditions do not support nucleation if only the key adaptor AP-2 is included, due to its insufficient abundance. Nucleation requires a stoichiometry of adaptor to clathrin that exceeds 1:1, meaning additional adaptor types are necessary to form lattices successfully and efficiently. We show that the critical nucleus contains ~25 clathrin, remarkably similar to sizes of the transient and abortive structures observed in vivo. Lastly, we quantify the cost of bending the membrane under our curved clathrin lattices using a continuum membrane model. We find that the cost of bending the membrane could be largely offset by the energetic benefit of forming curved rather than flat structures, with numbers comparable to experiments. Our model predicts how adaptor density can tune clathrin-coated structures from the transient to the stable, showing that active energy consumption is therefore not required for lattice disassembly or remodeling during growth, which is a critical advance towards predicting productive vesicle formation., Competing Interests: The authors have declared that no competing interests exist.

Exon back-splicing-generated circular RNAs, as a group, can suppress double-stranded RNA (dsRNA)-activated protein kinase R (PKR) in cells. We have sought to synthesize immunogenicity-free, short dsRNA-containing RNA circles as PKR inhibitors. Here, we report that RNA circles synthesized by permuted self-splicing thymidylate synthase (td) introns from T4 bacteriophage or by Anabaena pre-tRNA group I intron could induce an immune response. Autocatalytic splicing introduces ∼74 nt td or ∼186 nt Anabaena extraneous fragments that can distort the folding status of original circular RNAs or form structures themselves to provoke innate immune responses. In contrast, synthesized RNA circles produced by T4 RNA ligase without extraneous fragments exhibit minimized immunogenicity. Importantly, directly ligated circular RNAs that form short dsRNA regions efficiently suppress PKR activation 10 3 - to 10 6 -fold higher than reported chemical compounds C16 and 2-AP, highlighting the future use of circular RNAs as potent inhibitors for diseases related to PKR overreaction., Competing Interests: Declaration of interests L.-L.C., C.-X.L., S.-K.G., and Y.-F.X. are named as inventors on patents related to circular RNA held by the CAS CEMCS. L.-L.C. is a member of the Molecular Cell advisory board., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Circular RNAs are produced from back-splicing of exons of precursor mRNAs (pre-mRNAs). The sequences of exons in circular RNAs are identical to their linear cognate mRNAs, but the circular format may confer constraints on their folding and conformation, leading to potentially different functions from their linear RNA cognates. Here, we describe experimental and computational steps that optimize the selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) to probe circular RNA secondary structure at single-nucleotide resolution in living cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception., Methods: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses., Results: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis., Conclusion: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis., (© 2021 Royal Australasian College of Surgeons.)

The peach fruit moth (PFM), Carposina sasakii Matsumura, is a major phytophagous orchard pest widely distributed across Northeast Asia. Here, we report the chromosome-level genome for the PFM, representing the first genome for the family Carposinidae, from the lepidopteran superfamily Copromorphoidea. The genome was assembled into 404.83 Mb sequences using PacBio long-read and Illumina short-read sequences, including 275 contigs, with a contig N50 length of 2.62 Mb. All contigs were assembled into 31 linkage groups assisted by the Hi-C technique, including 30 autosomes and a Z chromosome. BUSCO analysis showed that 98.3% of genes were complete and 0.4% of genes were fragmented, while 1.3% of genes were missing in the assembled genome. In total, 21,697 protein-coding genes were predicted, of which 84.80% were functionally annotated. Because of the importance of diapause triggered by photoperiod in PFM, five circadian genes in the PFM as well as in the other related species were annotated, and potential genes related to diapause and photoperiodic reaction were also identified from transcriptome sequencing. In addition, manual annotation of detoxification gene families was undertaken and showed a higher number of glutathione S-transferase (GST) gene in PFM than in most other lepidopterans, in contrast to a lower number of uridine diphosphate (UDP)-glycosyltransferase (UGT) gene, carboxyl/cholinesterases (CCE) gene and cytochrome P450 monooxygenase (P450) gene, suggesting different detoxication pathways in this moth. The high-quality genome provides a resource for comparative evolutionary studies of this moth and its relatives within the context of radiations across Lepidoptera., (© 2020 John Wiley & Sons Ltd.)

Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are required to improve its antifungal activity. Our work in this paper focused on the replacement of oxazole ring in streptochlorin with the imidazole ring, to discover novel analogues. Based on this design strategy, three series of streptochlorin analogues were efficiently synthesized through sequential Vilsmeier-Haack reaction, Van Leusen imidazole synthesis and halogenation reaction. Some of the analogues displayed excellent activity in the primary assays, and this is highlighted by compounds 4g and 4i, the growth inhibition against Alternaria Leaf Spot and Rhizoctorzia solani under 50 μg/mL are 97.5% and 90.3%, respectively, even more active than those of streptochlorin, pimprinine and Osthole. Molecular docking models indicated that streptochlorin binds with Thermus thermophiles Leucyl-tRNA Synthetase in a similar mode to AN2690, offering a perspective on the mode of action study for antifungal activities of streptochlorin derivatives. Further study is still ongoing with the aim of discovering synthetic analogues, with improved antifungal activity and clear mode of action., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Putative mechanisms underlying spinosyn resistance have been identified in controlled studies on many species; however, mechanisms underlying field-evolved resistance and the development of a molecular diagnostic method for monitoring field resistance have lagged behind. Here, we examined levels of resistance of melon thrips, Thrips palmi Karny (Thysanoptera:Thripidae), to spinetoram as well as target site mutations in field populations across China to identify potential mechanisms and useful molecular markers for diagnostic and quantifying purposes. In resistant populations, we identified the G275E mutation, which has previously been linked to spinosyns resistance, and F314V mutation, both located in the α6 subunit of the nicotinic acetylcholine receptor. There was a strong correlation between levels of spinetoram resistance and allele frequency of G275E mutation in field-collected populations (r2 = 0.84) and those reared under laboratory conditions for two to five generations (r2 = 0.91). LC50 ranged from 0.12 to 0.66 mg/liter in populations without G275E mutation, whereas it ranged from 33.12 to 39.91 mg/liter in most populations with a G275E mutation frequency more than 90%. Our results indicate that the field-evolved resistance of T. palmi to spinetoram in China is mainly conferred by the G275E mutation. The frequency of the G275E mutation provides a useful diagnostic for quantifying resistance levels in field populations of T. palmi., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized through diversity-oriented synthesis strategy under the optimized conditions. Biological assays showed the designed derivatives exhibited potential activity.

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR-RfxCas13d can effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type-specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation by preventing the mRNA for family with sequence similarity 120A (FAM120A) from binding the translation inhibitor IGF2BP2. Further application of RfxCas13d-BSJ-gRNA screening has uncovered circMan1a2, which has regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR-RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.

Orphan and conventional kinesin dimers represent two families of the kinesin superfamily molecular motors. Conventional kinesin, having a 14-residue neck linker (NL) in each head, can step processively on microtubule (MT), with an ATP hydrolysis being coupled with a mechanical stepping under no load. Orphan kinesin phragmoplast-associated kinesin-related protein 2 (PAKRP2) dimer, despite having a NL of 32 residues in each head, can also step processively on MT and exhibits tight chemomechanical coupling under no load. However, the dynamic properties of the wild type PAKRP2 and the mutant one with each NL truncated to 14 residues are very different from those of the wild type conventional kinesin and the mutant one with each NL being replaced by the 32-residue NL from PAKRP2. Here, based on a common chemomechanical coupling model we study computationally the dynamics of the two families of the kinesin dimers, with the simulated results explaining quantitatively the available experimental data. The large differences in the dynamics between the two families of kinesin dimers arise mainly from different rate constants of NL docking and ATPase activity and different weak affinities of the head in ADP state for MT. The studies indicate that both the orphan kinesin PAKRP2 and conventional kinesin use the same mechanism for processive motility., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS., Methods and Analysis: We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.

Thrips are tiny insects from the order Thysanoptera (Hexapoda: Condylognatha), including many sap-sucking pests that are causing increasing damage to crops worldwide. In contrast to their closest relatives of Hemiptera (Hexapoda: Condylognatha), including numerous sap-sucking species, there are few genomic resources available for thrips. In this study, we assembled the first thrips genome at the chromosomal level from the melon thrips, Thrips palmi, a notorious pest in agriculture, using PacBio long-read and Illumina short-read sequences. The assembled genome was 237.85 Mb in size, with 1,324 contigs and a contig N50 of 567 kb. All contigs were assembled into 16 linkage groups assisted by the Hi-C technique. In total, 16,333 protein-coding genes were predicted, of which 88.13% were functionally annotated. Among sap-sucking insects, polyphagous species (e.g., T. palmi and Bemisia tabaci) usually possess more detoxification genes than oligophagous species (e.g., Diaphorina citri). The polyphagous thrips genomes characterized so far have relatively more detoxification genes in the GST and CCE families than polyphagous aphids, but they have fewer UGTs. HSP genes, especially from the Hsp70s group, have expanded in thrips compared to other hemipterans. These differences point to different genetic mechanisms associated with detoxification and stress responses in these two groups of sap-sucking insects. The expansion of these gene families may contribute to the rapid development of pesticide resistance in thrips, as supported by a transcriptome comparison of resistant and sensitive populations of T. palmi. The high-quality genome developed here provides an invaluable resource for understanding the ecology, genetics, and evolution of thrips as well as their relatives more generally., (© 2020 John Wiley & Sons Ltd.)

The melon thrips, Thrips palmi , is an increasingly important pest of vegetables in northern China. Some populations have developed resistance in the field to the insecticide spinetoram. Understanding the origin and dispersal of insecticide-resistant populations can shed light on resistance management strategies. In this study, we tested susceptibility of seven greenhouse populations of T. palmi to spinetoram collected from a small area of about 300 km 2 in Shandong Province and examined population genetic structure across the area based on a segment of mitochondrial cox1 gene and 22 microsatellite loci to infer the possible origin and dispersal of insecticide resistance. Levels of resistance to spinetoram differed among seven populations, which included one population with high resistance (LC 50  = 759.34 mg/L), three populations with medium resistance (LC 50 ranged from 28.69 to 34.79 mg/L), and three populations with low resistance (LC 50 ranged from 7.61 to 8.97 mg/L). The populations were genetically differentiated into two groups unrelated to both levels of resistance and geographic distance. The molecular data indicated high levels of gene flow between populations with different levels of resistance to spinetoram and low gene flow among populations with the same level of resistance, pointing to a likely separate history of resistance evolution. Resistance levels of two tested populations to spinetoram decreased 23 and 4.6 times after five generations without any exposure to the pesticide. We therefore suspect that resistance of T. palmi most likely evolved in response to local applications of the insecticide. Our study suggests that the development of resistance could be avoided or resistance even reversed by reducing usage of spinetoram., Competing Interests: None declared., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand-over-hand manner, transiting alternately between one-head-bound (1HB) and two-heads-bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all-atom molecular dynamics simulations we determined the position and orientation of the detached ADP-head relative to the MT-bound head in 1HB state. We showed that in 1HB state when the MT-bound head is in ADP or nucleotide-free state, with its neck linker being undocked, the detached ADP-head and the MT-bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT-bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head-head interaction in 1HB state were identified., (© 2019 Wiley Periodicals, Inc.)

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily. It has been experimentally revealed that in monomeric state kinesin-3 is inactive in motility and cargo-mediated dimerization results in superprocessive motion, with an average run length being more than 10-fold longer than that of kinesin-1. In contrast to kinesin-1 showing normally single-exponential distribution of run lengths, dimerized kinesin-3 shows puzzlingly Gaussian distribution of run lengths. Here, based on our proposed model, we studied computationally the dynamics of kinesin-3 and compared with that of kinesin-1, explaining quantitatively the available experimental data and revealing the origin of superprocessivity and Gaussian run length distribution of kinesin-3. Moreover, predicted results are provided on ATP-concentration dependence of run length distribution and force dependence of mean run length and dissociation rate of kinesin-3.

A general kinetic model is presented for the chemomechanical coupling of dimeric kinesin molecular motors with and without extension of their neck linkers (NLs). A peculiar feature of the model is that the rate constants of ATPase activity of a kinesin head are independent of the strain on its NL, implying that the heads of the wild-type kinesin dimer and the mutant with extension of its NLs have the same force-independent rate constants of the ATPase activity. Based on the model, an analytical theory is presented on the force dependence of the dynamics of kinesin dimers with and without extension of their NLs at saturating ATP. With only a few adjustable parameters, diverse available single molecule data on the dynamics of various kinesin dimers, such as wild-type kinesin-1, kinesin-1 with mutated residues in the NLs, kinesin-1 with extension of the NLs and wild-type kinesin-2, under varying force and ATP concentration, can be reproduced very well. Additionally, we compare the power production among different kinesin dimers, showing that the mutation in the NLs reduces the power production and the extension of the NLs further reduces the power production.

Kinesin is a biological molecular motor that can move continuously on microtubule until it unbinds. Here, we studied computationally the force dependence of the unbinding rate of the motor. Our results showed that while the unbinding rate under the forward load has the expected characteristic of "slip bond", with the unbinding rate increasing monotonically with the increase of the forward load, the unbinding rate under the backward load shows counterintuitive characteristic of "slip-catch-slip bond": as the backward load increases, the unbinding rate increases exponentially firstly, then drops rapidly and then increases again. Our calculated data are in agreement with the available single-molecule data from different research groups. The mechanism of the slip-catch-slip bond was revealed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Circular RNAs (circRNAs) produced from back-splicing of exons of pre-mRNAs are widely expressed, but current understanding of their functions is limited. These RNAs are stable in general and are thought to have unique structural conformations distinct from their linear RNA cognates. Here, we show that endogenous circRNAs tend to form 16-26 bp imperfect RNA duplexes and act as inhibitors of double-stranded RNA (dsRNA)-activated protein kinase (PKR) related to innate immunity. Upon poly(I:C) stimulation or viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients with autoimmune disease systemic lupus erythematosus (SLE). Importantly, overexpression of the dsRNA-containing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Intracellular transport is performed often by multiple motor proteins bound to the same cargo. Here, we study theoretically collective transport of the cargo by two kinesin motors. We propose that the motor has only the elastic interaction with the cargo via the linker connecting them and has no interaction with another motor. With parameters values for single motors from the available single-molecule data, we show that at linker's elastic strength [Formula: see text] pN/nm the theoretical data of both velocity and run length of the two-motor assembly under no load are identical to the available experimental data. The run length distribution is single exponential. The single-motor-bound state of the assembly dominates the transport. Both the force dependence of the velocity of the cargo driven by single load-bearing motor and that by two load-bearing motors in the assembly are consistent with the experimental data. The stall force of the assembly is larger than the sum of stall forces of two uncoupled motors. Moreover, we predict that the stall force increases with the increase of K and becomes saturated at large K, with the saturated value being 1.5-fold larger than the sum of stall forces of the two uncoupled motors.

A model is presented for the chemomechanical coupling of kinesin motors, which proposes that the rate constants of the chemical reaction are independent of the external force. On the basis of the model, we study theoretically the movement dynamics of the motors under varying external force and ATP concentration, such as the forward to backward stepping ratio, velocity, dwell time between two mechanical steps, stall force, and so on. The theoretical results reproduce quantitatively the diverse and even contradictory available single-molecule experimental data for different species of the motors. Furthermore, we study the dependence of the chemomechanical coupling ratio on ATP concentration and external force, with both ATP concentration and external force having large effects on the chemomechanical coupling.

Kinesin-1, kinesin-2 and kinesin-5 are three families of a superfamily of motor proteins; which can walk processively on microtubule filaments by hydrolyzing ATP. It was experimentally shown that while the three kinesin dimers show similar feature on the force dependence of velocity, they show rather different features on the force dependence of run length. However, why the three families of kinesins show these rather different features is unclear. Here, we computationally studied the movement dynamics of the three dimers based on our proposed model. The simulated results reproduce well the available experimental data on the force dependence of velocity and run length. Moreover, the simulated results on the velocity and run length for the three dimers with altered neck linker lengths are also in quantitative agreement with the available experimental data. The studies indicate that the three families of kinesins show much similar movement mechanism and the rather different features on the force dependence of run length arise mainly from the difference in rate constants of the ATPase activity and neck linker docking. Additionally, the asymmetric (limping) movement dynamics of the three families of homodimers with and without altered neck linker lengths are studied, providing predicted results., Competing Interests: The authors declare no conflict of interest.

Changes of affinity of kinesin head to microtubule regulated by changes in the nucleotide state are essential to processive movement of kinesin on microtubule. Here, using all-atom molecular dynamics simulations we show that besides the nucleotide state, large conformational changes of microtubule-tubulin heterodimers induced by strong interaction with the head in strongly binding state are also indispensable to regulate the affinity of the head to the tubulin. In strongly binding state the high affinity of the head to microtubule arises largely from mutual conformational changes of the microtubule and head induced by the specific interaction between them via an induced-fit mechanism. Moreover, the ADP-head has a much weaker affinity to the local microtubule-tubulin, whose conformation is largely altered by the interaction with the head in strongly binding state, than to other unperturbed tubulins. This indicates that upon Pi release the ADP-head temporarily has a much weaker affinity to the local tubulin than to other tubulins., (© 2018 Wiley Periodicals, Inc.)

Kinesin-1 is a homodimeric motor protein that can move along microtubule filaments by hydrolyzing ATP with a high processivity. How the two motor domains are coordinated to achieve such high processivity is not clear. To address this issue, we computationally studied the run length of the dimer with our proposed model. The computational data quantitatively reproduced the puzzling experimental data, including the dramatically asymmetric character of the run length with respect to the direction of external load acting on the coiled-coil stalk, the enhancement of the run length by addition of phosphate, and the contrary features of the run length for different types of kinesin-1 with extensions of their neck linkers compared with those without extension of the neck linker. The computational data on other aspects of the movement dynamics such as velocity and durations of one-head-bound and two-head-bound states in a mechanochemical coupling cycle were also in quantitative agreement with the available experimental data. Moreover, predicted results are provided on dependence of the run length upon external load acting on one head of the dimer, which can be easily tested in the future using single-molecule optical trapping assays.

Background/aims: Transforming growth factor beta-induced protein (TGFBI) is an extracellular matrix protein induced by TGF-β. Previous studies have reported that the abnormal expression of TGFBI is related to the occurrence and development of some types of cancers, while the role of TGFBI in glioma is uncertain., Methods: The association between TGFBI expression and the prognosis of patients with glioma was analyzed based on data obtained from The Cancer Genome Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57 cases of human gliomas by immunohistochemistry followed by an evaluation of the relationships between TGFBI expression and clinic-pathological features. Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and transfected into U87 and U251 cells to explore the effect of short hairpin RNA against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis. Western blot analysis was performed to examine the expression of proteins related to apoptosis and proteins in the PI3K/Akt signaling pathway., Results: High TGFBI expression was found to be associated with poor prognosis in patients with glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was significantly higher in glioma tissue than in normal human brain tissues. The expression level of TGFBI showed no significant correlation with age, sex, lymph-node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation, invasion and migration and induce apoptosis in U87 and U251 cells in vitro. Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in sh-TGFBI transfected U81 and U251 cells when compared with control., Conclusion: TGFBI was up-regulated in glioma cells and played a promoting role in the growth and motility of U87 and U251 cells. These results suggested that TGFBI has the potential to be a diagnostic marker and to serve as a target for the treatment of gliomas., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Treatments for osteoarthritis (OA) seek to restore chondrocyte function and inhibit cell apoptosis. Panax quinquefolium saponin (PQS) is the major active ingredient of Radix panacis quinquefolii (American ginseng), and has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in various diseases. However, any potential effect of PQS on the pathological process of OA remains unclear. This work aimed to explore the role of PQS in chondrocytes and to clarify its potential mechanisms. We showed that PQS treatment could protect chondrocytes against endoplasmic reticulum (ER) stress and associated apoptosis induced by interleukin (IL)-1β. Also, PQS further attenuated triglyceride (TG)-induced ER stress and associated apoptosis. Moreover, PQS may inhibit the ER stress-activated NF-κB pathway and associated inflammatory response in chondrocytes. Finally, PQS abolished rat cartilage degeneration in an in-vivo OA model of the knee joint. Our results indicate that PQS may be a potential novel treatment for OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Conventional kinesin (kinesin-1) can walk on microtubule filaments in an asymmetric hand-over-hand manner, exhibiting a marked alternation in the mean dwell time in successive steps. Here, we study computationally the asymmetric stepping dynamics of the kinesin-1 homodimer, revealing its origin and providing quantitative explanations of the available experimental data. The alternation in the mean dwell time in successive steps arises from the alternation in the mechanochemical coupling ratio, which is in turn caused by the alternation in the slight variation of the stretched neck linker length. Both the vertical and backward longitudinal forces can enhance the asymmetric ratio. Additionally, other aspects of the stepping dynamics of the dimer such as the velocity versus longitudinal force, extended neck linker, etc., are also studied. In particular, the conflicting experimental data, with some showing that the velocity does not change with the forward longitudinal load while others showing that the velocity increases largely with the forward longitudinal load, are explained quantitatively and consistently. The intriguing experimental data showing that cysteine-light Drosophila and human kinesin-1 mutants have different load-dependent velocity from the wild-type cases as well as that kinesin-2 dimers have different load-dependent velocity from the kinesin-1 are also explained consistently and quantitatively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

BACKGROUND This study aimed to compare the efficacy and prognostic value of partial sensory rhizotomy (PSR) and microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). MATERIAL AND METHODS From June 2010 to June 2012, 117 patients with PTN were recruited for the study, of which 52 cases were treated with MVD (the MVD group) and 65 cases were treated with PSR (the PSR group). Visual Analog Scoring (VAS) was performed at 1 and 2 weeks, and at 1, 3, and 6 month after surgery. The overall response rate (ORR) was determined 1 month after surgery. Barrow Neurological Institute score was adopted to value the reoccurrence at 6, 12, 24, and 36 months after surgery. A 3-year follow-up was conducted and the complications were recorded. RESULTS The ORR 2 weeks after surgery in the MVD and PSR groups was 98.08% and 84.62%, respectively. One and 2 weeks after surgery, the VAS was lower in the MVD group than in the PSR group, but there was no significant difference in VAS between the 2 groups at 1, 3, and 6 months after surgery. Three years after surgery, the recurrence rate was significantly lower in the MVD group than in the PSR group. The recurrence-free survival time was longer in the MVD group than in the PSR group. The occurrence rates of herpes and total postoperative complications were significantly higher in the PSR group than in the MVD group. CONCLUSIONS Compared with PSR, MVD is more suitable for PTN treatment, with less disturbance, lower recurrence rate, and better efficacy.

Dimeric kinesin can move processively on microtubule filaments by hydrolyzing ATP. Diverse aspects of its movement dynamics have been studied extensively by using various experimental methods. However, the detailed molecular mechanism of the processive movement is still undetermined and a model that can provide a consistent and quantitative explanation of the diverse experimental data is still lacking. Here, we present such a model, with which we study the movement dynamics of the dimer under variations of solution viscosity, external load, ATP concentration, neck linker length, effect of neck linker docking, effect of a large-size particle attached to one kinesin head, etc., providing consistent and quantitative explanations of the available diverse experimental data. Moreover, predicted results are also provided., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines.

Objective: To determine the feasibility and accuracy of detecting numerical chromosomal abnormalities by high-flux sequencing analysis of free fetal DNA from maternal plasma., Methods: High-flux sequencing was applied to analyze fetal chromosome sequence copy numbers in 153 pregnant women. Fetal karyotyping was also carried out on amniocentesis samples., Results: Six cases were detected with fetal chromosomal abnormalities by high-flux sequencing analysis, among which five were confirmed by karyotyping to be chromosomal aneuploidies (47,XYY; 45,X; 47,XY,+18; 47,XY,+21 and 47,XY,+13), 1 case was confirmed to be structural rearrangement, i.e., 46,XY,der(13;21)(q10;q10),+21. Furthermore, 3 chromosomal polymorphisms (one 46,XY,21p+ and two 46,XY,Yqh-) were identified. The two methods yielded similar results on fetal chromosome copy number detection., Conclusion: High-flux sequencing analysis of free DNA derived from maternal plasma is efficient for detecting fetal chromosomal aneuploidies, and is non-invasive, highly sensitive and specific. It therefore has a broad application in antenatal diagnosis.

The use of the microwave tissue coagulator was studied on 20 consecutive elective hepatic resections carried out for symptomatic hepatocellular carcinoma with liver cirrhosis. The mean operative blood loss (excluding one patient with hepatic vein injury) was 1132 mL. Five patients required no blood transfusion. The average time taken to coagulate the anticipated liver transection plane was less than 15 min. Apart from the complications similar to those occurring in hepatic resections for cirrhotic patients, higher incidences of intra-abdominal sepsis (20%), sympathetic pleural effusion in the absence of chest or intra-abdominal sepsis (20%), and persistent fever lasting more than 1 week (40%) were encountered. It was considered that these complications were related to the coagulated tissue present in the liver remnants (mean depth of tissue coagulation = 3.8 mm) and concluded that although the hospital mortality rate of 10% and the mean operative blood loss of 1132 mL were acceptably low, microwave liver surgery carried a high morbidity rate which is a drawback in major hepatic resectional surgery.