An efficient and accurate multi-level cascaded recurrent network for stereo matching.

With the advent of Transformer-based convolutional neural networks, stereo matching algorithms have achieved state-of-the-art accuracy in disparity estimation. Nevertheless, this method requires much model inference time, which is the main reason limiting its application in many vision tasks and robots. Facing the trade-off problem between accuracy and efficiency, this paper proposes an efficient and accurate multi-level cascaded recurrent network, LMCR-Stereo. To recover the detailed information of stereo images more accurately, we first design a multi-level network to update the difference values in a coarse-to-fine recurrent iterative manner. Then, we propose a new pair of slow-fast multi-stage superposition inference structures to accommodate the differences between different scene data. Besides, to ensure better disparity estimation accuracy with faster model inference speed, we introduce a pair of adaptive and lightweight group correlation layers to reduce the impact of erroneous rectification and significantly improve model inference speed. The experimental results show that the proposed approach achieves a competitive disparity estimation accuracy with a faster model inference speed than the current state-of-the-art methods. Notably, the model inference speed of the proposed approach is improved by 46.0% and 50.4% in the SceneFlow test set and Middlebury benchmark, respectively.

Intermolecular Interactions, Morphology, and Photovoltaic Patterns in p-i-n Heterojunction Solar Cells With Fluorine-Substituted Organic Photovoltaic Materials.

During the layer-by-layer (LBL) processing of polymer solar cells (PSCs), the swelling and molecule interdiffusion are essential for achieving precise, controllable vertical morphology, and thus efficient PSCs. However, the influencing mechanism of material properties on morphology and correlated device performance has not been paid much attention. Herein, a series of fluorinated/non-fluorinated polymer donors (PBDB-T and PBDB-TF) and non-fullerene acceptors (ITIC, IT-2F, and IT-4F) are employed to investigate the performance of LBL devices. The impacts of fluorine substitution on the repulsion and miscibility between the donor and acceptor, as well as the molecular arrangement of the donor/acceptor and the vertical distribution of the LBL devices are systematically explored by the measurement of donor/acceptor Flory-Huggins interaction parameters, spectroscopic ellipsometry, and neutron reflectivity, respectively. With efficient charge transfer due to the ideal vertical and horizon morphology properties, devices based on PBDB-TF/IT-4F exhibit the highest fill factors (FFs) as well as champion power conversion efficiencies (PCEs). With this guidance, high-performance LBL devices with PCE of 17.2%, 18.5%, and 19.1% are obtained by the fluorinated blend of PBDB-TF/Y6, PBDB-TF/L8-BO, and D18/L8-BO respectively.

Association Analysis of Gut Microbiota and Prognosis of Patients with Acute Ischemic Stroke in Basal Ganglia Region.

Previous studies have implied the potential impact of gut microbiota on acute ischemic stroke (AIS), but the relationships of gut microbiota with basal ganglia region infarction (BGRI) and the predictive power of gut microbiota in BGRI prognosis is unclear. The aim of this study was to ascertain characteristic taxa of BGRI patients with different functional outcomes and identify their predictive value. Fecal samples of 65 BGRI patients were collected at admission and analyzed with 16s rRNA gene sequencing. Three-month functional outcomes of BGRI were evaluated using modified Rankin Scale (mRS), and patients with mRS score of 0-1 were assigned to good-BGRI group while others were assigned to poor-BGRI group. We further identified characteristic microbiota using linear discriminant analysis effect size, and receiver operating characteristic (ROC) curve was used to determine the predictive value of differential bacteria. According to the mRS score assessed after 3 months of stroke onset, 22 patients were assigned to poor-BGRI group, while 43 patients were assigned to good-BGRI group. Short chain fatty acids-producing bacteria, Romboutsia and Fusicatenibacter, were characteristic microbiota of the good-BGRI group, while pro-inflammatory taxa, Acetanaerobacterium, were characteristic microbiota of the poor-BGRI group. Furthermore, the differential bacteria showed extensive associations with clinical indices. ROC curves, separately plotted based on Romboutsia and Fusicatenibacter, achieved area under the curve values of 0.7193 and 0.6839, respectively. This study identified the efficient discriminative power of characteristic microbiota in BGRI patients with different outcomes and provided novel insights into the associations of gut microbiota with related risk factors.

Association analysis of the gut microbiota in predicting outcomes for patients with acute ischemic stroke and H-type hypertension.

Introduction: H-type hypertension (HHTN) is a subtype of hypertension that tends to worsen the prognosis of acute ischemic stroke (AIS). Recent studies have highlighted the vital role of gut microbiota in both hypertension and AIS, but there is little available data on the relationship between gut microbiota and the progression of AIS patients with HHTN. In this study, we investigated the microbial signature of AIS patients with HHTN and identified characteristic bacteria as biomarkers for predicting prognosis. Methods: AIS patients with HHTN (n = 150) and without HHTN (n = 50) were enrolled. All patients received a modified Rankin Scale (mRS) assessment at 3 months after discharge. Fecal samples were collected from the participants upon admission, including 150 AIS patients with HHTN, 50 AIS patients with non-HHTN, and 90 healthy subjects with HHTN. These samples were analyzed using 16S rRNA sequencing to characterize the bacterial taxa, predict functions, and conduct correlation analysis between specific taxa and clinical features. Results: Our results showed that the composition of the gut microbiota in HHTN patients differed significantly from that in non-HHTN patients. The abundance of the genera Bacteroides, Escherichia-Shigella, Lactobacillus, Bifidobacterium, and Prevotella in AIS patients with HHTN was significantly increased compared to AIS patients without HHTN, while the genus Streptococcus, Faecalibacterium, and Klebsiella were significantly decreased. Moreover, Bacteroides, Lactobacillus, Bifidobacterium, and Klebsiella in AIS patients with HHTN were more abundant than healthy subjects with HHTN, while Escherichia-Shigella, Blautia, and Faecalibacterium were less abundant. Moreover, the genera Butyricicoccus, Rothia, and Family_XIII_UCG-001 were negatively connected with the NIHSS score, and the genera Butyricicoccus and Rothia were observed to be negatively associated with the mRS score. The genera Butyricicoccus, Romboutsia, and Terrisporobacter were associated with a poor prognosis, whereas the increase in Butyricimonas and Odoribacter was correlated with good outcomes. Generated by eight genera and clinical indexes, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve achieved 0.739 to effectively predict the prognosis of AIS patients with HHTN. Conclusion: These findings revealed the microbial signature of AIS patients with HHTN and further provided potential microbial biomarkers for the clinical diagnosis of AIS patients with HHTN.

Functional analysis of UDP-glycosyltransferase genes conferring indoxacarb resistance in Spodoptera litura.

UDP-glycosyltransferase (UGT) is the major detoxification enzymes of phase II involved in xenobiotics metabolism, which potentially mediates the formation of insect resistance. Previous transcriptome sequencing studies have found that several UGT genes were upregulated in indoxacarb resistant strains of Spodoptera litura, but whether these UGT genes were involved in indoxacarb resistance and their functions in resistance were unclear. In this study, the UGTs inhibitor, 5-nitrouracil, enhanced the toxicity of indoxacarb against S. litura, preliminarily suggesting that UGTs were participated in indoxacarb resistance. Two UGT genes, UGT33J17 and UGT41D10 were upregulated in the resistant strains and could be induced by indoxacarb. Alignment of UGT protein sequences revealed two conserved donor-binding regions with several key residues that interact with catalytic sites and sugar donors. Further molecular modeling and docking analysis indicated that two UGT proteins were able to stably bind indoxacarb and N-decarbomethoxylated metabolite (DCJW). Furthermore, knockdown of UGT33J17 and UGT41D10 decreased viability of Spli-221 cells and enhanced susceptibility of larvae to indoxacarb. Transgenic overexpression of these genes reduced the toxicity of indoxacarb in Drosophila melanogaster. This work revealed that upregulation of UGT genes significantly contributes to indoxacarb resistance in S. litura, and is of great significance for the development of integrated and sustainable management strategies for resistant pests in the field.

A Sensitive Method for Detecting Beauveria bassiana, an Insecticidal Biocontrol Agent, Population Dynamics, and Stability in Different Substrates.

Beauveria bassiana is a well-known insecticidal biocontrol agent. Despite its broad field applications, its survival, colonization, and stability under field conditions remained unclear, mainly due to the lack of a quick and reliable detection method. In this study, we developed a quantitative real-time PCR technology to monitor the stability and population dynamics of B. bassiana in different substrates (water, soil, and on the cotton leaves surface), different spores of B. bassiana applied on Chinese cabbage leaves surface, and the lethality of Pieris rapae spraying with different spores of B. bassiana. Our results showed a decreased concentration of B. bassiana DNA in all three substrates from the 1st day till 9th day of post inoculation (dpi) period, possibly due to the death of B. bassiana. After this decrease, a quick and significant rebound of B. bassiana DNA concentration was observed, starting from the 11th dpi in all three substrates. The B. bassiana DNA concentration reached the plateau at about 13th dpi in water and 17th dpi in the soil. On cotton leaves surface, the B. bassiana DNA concentration reached the highest level at the 17th dpi followed by a small decline and then stabilized. This increase of DNA concentration suggested recovery of B. bassiana growth in all three substrates. We found that the most suitable killing effectiveness of P. rapae was the 1.0 × 107 spores/mL of B. bassiana. In summary, we have established a detection technology that allows a fast and reliable monitoring for the concentration and stability of B. bassiana under different conditions. This technology can benefit and help us in the development of proper management strategies for the application of this biocontrol agent in the field.

Peripheral Neuropathy in Older People Is Associated with Reduced Life Expectancy.

INTRODUCTION: We analyzed data from a prospective cohort of older primary care patients to determine whether the presence of peripheral neuropathy (PN) was associated with premature mortality and to investigate potential mechanisms. METHODS: PN was defined as the presence of 1 or more bilateral lower extremity sensory deficits detectable by physical examination. Mortality was determined from key contacts and Internet sources. Statistical models were used to evaluate the association between PN and mortality. RESULTS: Bilateral lower extremity neurological deficits were common, reaching 54% in those 85 and older. PN was strongly associated with earlier mortality. Mean survival time for those with PN was 10.8 years, compared with 13.9 years for subjects without PN. PN was also indirectly associated through impaired balance. CONCLUSIONS: In this relatively healthy cohort of older primary care patients, PN detectable by physical examination was extremely common and strongly associated with earlier mortality. One possible mechanism involves loss of balance, though our data were insufficient to determine whether poor balance led to injurious falls or to less-specific declines in health. These findings may warrant further studies to determine the causes of age-associated PN and potential impact of early detection and balance improvement and other fall prevention strategies.

Predatory Capacity and Reproduction of Cyrtorhinus lividipennis (Hemiptera: Miridae) Adults Exposed to Low-Temperature Storage and Fitness of the F1 Generation.

Low-temperature storage (LTS) is a way to adjust natural enemy development to meet field release needs and to protect natural enemies from the odds of long-distance transportation. The mirid bug Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important predator of planthoppers and leafhoppers in rice fields. In this study, the LTS effects were measured on the predatory capacity and reproduction of the mirid adults (provided with 20% honey solution and stored at 13 °C for 12 days), and the fitness of the F1 generation of these adults. Higher predation of the eggs of the brown planthopper Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) was observed in the post-storage females than in the control females. The functional responses of C. lividipennis adults, either exposed to LTS or not, to planthopper eggs fitted well with Holling type II functional responses. Longevity was not affected by LTS, whereas the number of offspring nymphs was 55.6% lower in the post-storage females than in the control females. The fitness of the offspring generation was not affected by the LTS of parental adults. The findings are discussed with their relevance to biological control.

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System.

Purpose: Gastrointestinal perforation (GIP) is a fatal adverse event (AE). The AE of GIP induced by novel antineoplastic agents has attracted attention recently. We aimed to explore the AE signals of GIP related to novel antineoplastic agents comprehensively based on the FDA Adverse Event Reporting System (FAERS). Methods: The FAERS database containing 71 quarters of records was used for analysis. Reporting odds ratio (ROR), information component (IC), and empirical Bayesian geometric mean (EBGM) were utilized to evaluate the signals of GIP associated with novel antineoplastic drugs. Standardization of drug names was by employing MedEx-UIMA software and Python. Data analysis and visualization were performed using MySQL Workbench and R software. Results: After cleaning and handling the data, 5226 GIP cases were identified that were associated with new antineoplastic medications, where these agents were the main suspected contributors. A total of 37 novel antineoplastic drugs were detected with signals of GIP for ROR and IC. Only 22 drugs showed statistically significant signals for EBGM. We found the GIP signals of 22 novel antineoplastic drugs overlapped for the 3 indicators, including anti-vascular endothelial growth factor/vascular endothelial growth factor receptor, anti-endothelial growth factor receptor, immune checkpoint inhibitors, and so on. Conclusion: The potential risk of GIP associated with several novel antineoplastic agents was identified through data mining, which provided valuable information on the safety risks associated with GIP among these drugs. The potential threat of GIP should be recognized and managed properly when using these novel antineoplastic agents.

Semi-Supervised Medical Image Segmentation Guided by Bi-Directional Constrained Dual-Task Consistency.

BACKGROUND: Medical image processing tasks represented by multi-object segmentation are of great significance for surgical planning, robot-assisted surgery, and surgical safety. However, the exceptionally low contrast among tissues and limited available annotated data makes developing an automatic segmentation algorithm for pelvic CT challenging. METHODS: A bi-direction constrained dual-task consistency model named PICT is proposed to improve segmentation quality by leveraging free unlabeled data. First, to learn more unmarked data features, it encourages the model prediction of the interpolated image to be consistent with the interpolation of the model prediction at the pixel, model, and data levels. Moreover, to constrain the error prediction of interpolation interference, PICT designs an auxiliary pseudo-supervision task that focuses on the underlying information of non-interpolation data. Finally, an effective loss algorithm for both consistency tasks is designed to ensure the complementary manner and produce more reliable predictions. RESULTS: Quantitative experiments show that the proposed PICT achieves 87.18%, 96.42%, and 79.41% mean DSC score on ACDC, CTPelvic1k, and the individual Multi-tissue Pelvis dataset with gains of around 0.8%, 0.5%, and 1% compared to the state-of-the-art semi-supervised method. Compared to the baseline supervised method, the PICT brings over 3-9% improvements. CONCLUSIONS: The developed PICT model can effectively leverage unlabeled data to improve segmentation quality of low contrast medical images. The segmentation result could improve the precision of surgical path planning and provide input for robot-assisted surgery.

Autonomous path planning for robot-assisted pelvic fracture closed reduction with collision avoidance.

BACKGROUND: Robot-assisted pelvic fracture closed reduction (RPFCR) positively contributes to patient treatment. However, the current path planning suffers from incomplete obstacle avoidance and long paths. METHOD: A collision detection method is proposed for applications in the pelvic environment to improve the safety of RPFCR surgery. Meanwhile, a defined orientation planning strategy (OPS) and linear sampling search (LSS) are coupled into the A* algorithm to optimise the reduction path. Subsequently, pelvic in vitro experimental platform is built to verify the augmented A*algorithm's feasibility. RESULTS: The augmented A* algorithm planned the shortest path for the same fracture model, and the paths planned by the A* algorithm and experience-based increased by 56.12% and 89.02%, respectively. CONCLUSIONS: The augmented A* algorithm effectively improves surgical safety and shortens the path length, which can be adopted as an effective model for developing RPFCR path planning.

Gut microbiota alterations are associated with functional outcomes in patients of acute ischemic stroke with non-alcoholic fatty liver disease.

Introduction: Patients with acute ischemic stroke (AIS) with non-alcoholic fatty liver disease (NAFLD) frequently have poor prognosis. Many evidences suggested that the changes in gut microbiota may play an important role in the occurrence and development of AIS patients with NAFLD. The purpose of this study was to explore microbial characteristics in patients of AIS with NAFLD, and the correlation between gut microbiota and functional outcomes. Methods: The patients of AIS were recruited and divided into NAFLD group and non-NAFLD group. The stool samples and clinical information were collected. 16 s rRNA sequencing was used to analyze the characteristics of gut microbiota. The patients of AIS with NAFLD were followed-up to evaluate the functional outcomes of disease. The adverse outcomes were determined by modified Rankin scale (mRS) scores at 3 months after stroke. The diagnostic performance of microbial marker in predicting adverse outcomes was assessed by recipient operating characteristic (ROC) curves. Results: Our results showed that the composition of gut microbiota between non-NAFLD group and NAFLD group were different. The characteristic bacteria in the patients of AIS with NAFLD was that the relative abundance of Dorea, Dialister, Intestinibacter and Flavonifractor were decreased, while the relative abundance of Enorma was increased. Moreover, the characteristic microbiota was correlated with many clinical parameters, such as mRS scores, mean arterial pressure and fasting blood glucose level. In addition, ROC models based on the characteristic microbiota or the combination of characteristic microbiota with independent risk factors could distinguish functional dependence patients and functional independence patients in AIS with NAFLD (area under curve is 0.765 and 0.882 respectively). Conclusion: These findings revealed the microbial characteristics in patients of AIS with NAFLD, and further demonstrated the predictive capability of characteristic microbiota for adverse outcomes in patients of AIS with NAFLD.

Torsade de Pointes/QT Prolongation Associated with Antifungal Triazoles: A Pharmacovigilance Study Based on the U.S. FDA Adverse Event Reporting System（FAERS）.

PURPOSE: Torsade de pointes (TdP)/QT prolongation is a fatal adverse event (AE) when using antifungal triazoles. We aimed to compare the AE signals of TdP/QT prolongation and onset time among different drugs of this kind comprehensively. METHODS: This retrospective research was to analyze the U.S. FDA Adverse Event Reporting System (FAERS) database containing 71 quarters of reports through online retrieval. We calculated the strength of signals of TdP/QT prolongation related to 4 drugs of triazoles by using the following indicators: reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). The onset time to the AE of TdP/QT prolongation among different antifungal triazoles were compared by using nonparametric tests. Management and visualization of the data were performed by employing MySQL Workbench and R software. The data information including clinical features, AE onset time, and outcomes were extracted for analysis as well. RESULTS: After filtering the FAERS database, 448 reports were identified that were associated with TdP/QT prolongation when 4 triazoles played the primary suspected role.  The AE signals of TdP/QT prolongation for any involved antifungal triazoles were detected by using the 4 detection indicators, and the signals of fluconazole are the strongest. This AE mostly occurred within 0-14 days after triazoles therapy. CONCLUSIONS: The AE signals of TdP/QT prolongation associated with antifungal triazoles were very intense. Attention must be paid to the TdP/QT prolongation of various triazoles, particularly at the early stages of antifungal triazoles treatment.

Effects of Four Cropping Patterns of Lilium brownii on Rhizosphere Microbiome Structure and Replant Disease.

Replant disease caused by continuous cropping obstacles commonly occurs in a Lilium brownii consecutive monoculture. To reveal the mechanisms contributing to the continuous cropping obstacles of L. brownii, four cropping patterns (fallow, L. brownii-rice rotation, newly planted L. brownii, and 2-year L. brownii consecutive monoculture) were designed, and Illumina MiSeq (16S rDNA and ITS) was utilized to detect shifts in the microbial community in the rhizosphere. Our result showed that planting of L. brownii significantly reduced soil pH. Consecutive monoculture of L. brownii can significantly decrease the diversity and abundance of soil bacteria, but markedly increase the diversity and abundance of soil fungi. Under the four planting pattern treatments, the changes in soil pH were consistent with the changes in the Shannon diversity index of soil bacterial communities, whereas we observed a negative correlation between soil pH and Shannon diversity index for fungi. The relative abundance of Lactobacillales significantly increased in soils of L. brownii consecutive monoculture, while Acidobacteriales, Solibacterales, and Xanthomonadales increased in soils of L. brownii-rice rotation and newly planted L. brownii. Collectively, this work aimed to elucidate the relationship between the L. brownii planting patterns and soil microbiome, thereby providing a theoretical basis for screening new biological agents that may contribute to resolving continuous cropping obstacles of L. brownii.

Systematic identification and functional analysis of long noncoding RNAs involved in indoxacarb resistance in Spodoptera litura.

Long noncoding RNAs (lncRNAs) are noncoding transcripts that are more than 200 nucleotides long. They play essential roles in regulating a variety of biological processes in many species, including insects, and some lncRNAs have been found to be associated with insecticide resistance. However, the characteristics and biological functions of lncRNAs involved in indoxacarb resistance are unknown in Spodoptera litura. We performed RNA sequencing in the SS, InRS, and FInRS of S. litura and identified 11 978 lncRNAs, including 3 136 intergenic lncRNAs, 7 393 intronic lncRNAs, and 1 449 anti-sense lncRNAs. Compared with the SS, 51 lncRNAs were upregulated and 134 lncRNAs were downregulated in the two resistant strains, and 908 differentially expressed mRNAs were predicted as the target genes of the 185 differentially expressed lncRNAs. Further analysis showed that 112 of differentially expressed lncRNAs may be associated with indoxacarb resistance by regulating the expression of 14 P450s, seven CCEs, one GST, six UGTs, five ABC transporters, and 24 cuticle protein genes, and 79 of differentially expressed lncRNAs may regulate the expression of 14 detoxification genes and 19 cuticle protein genes to participate in indoxacarb resistance by sponging 10 microRNAs. Interestingly, 47 of differentially expressed lncRNAs may mediate indoxacarb resistance through both lncRNA-mRNA and lncRNA-miRNA-mRNA regulatory pathways. Furthermore, quantitative PCR, RNA interference, and indoxacarb bioassay analyses indicated that overexpressed LNC_004867 and LNC_006576 were involved in indoxacarb resistance. This study provides comprehensive information for lncRNAs of S. litura, and presents evidence that lncRNAs have key roles in conferring insecticide resistance in S. litura.

Contribution of multiple overexpressed carboxylesterase genes to indoxacarb resistance in Spodoptera litura.

BACKGROUND: As an important family of detoxification enzymes, carboxylesterases (CarEs) have important roles in the development of insecticide resistance in almost all agricultural pests. Previous studies have suggested that enhancement of CarE activity is an important mechanism mediating indoxacarb resistance in Spodoptera litura, and several CarE genes have been found to be overexpressed in indoxacarb-resistant strains. However, the functions of these CarE genes in indoxacarb resistance needs to be further investigated. RESULTS: The synergist triphenyl phosphate effectively reduced the resistance of S. litura to indoxacarb, suggesting an involvement of CarEs in indoxacarb resistance. Among seven identified S. litura CarE genes (hereafter SlituCOE), six were overexpressed in two indoxacarb-resistant strains, but there were no significant differences in gene copy number. Knockdown of SlituCOE009 and SlituCOE050 enhanced indoxacarb sensitivity in both susceptible and resistant strains, whereas knockdown of SlituCOE090, SlituCOE093 and SlituCOE074 enhanced indoxacarb sensitivity in only the resistant strain. Knockdown of the sixth gene, SlituCOE073, did not have any effect. Furthermore, simultaneous knockdown of the five SlituCOE genes had a greater effect on increasing indoxacarb sensitivity than silencing them individually. By contrast, overexpression of the five SlituCOE genes individually in Drosophila melanogaster significantly decreased the toxicity of indoxacarb to transgenic fruit flies. Furthermore, modeling and docking analysis indicated that the catalytic pockets of SlituCOE009 and SlituCOE074 were ideally shaped for indoxacarb and N-decarbomethoxylated metabolite (DCJW), but the binding affinity for DCJW was stronger than for indoxacarb. CONCLUSION: This study reveals that multiple overexpressed CarE genes are involved in indoxacarb resistance in S. litura.

Thyroid dysfunction related to vascular endothelial growth factor receptor tyrosine kinase inhibitors: A real-world study based on FAERS.

WHAT IS KNOWN AND OBJECTIVE: The adverse events of thyroid dysfunction caused by the use of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have not been confirmed in a real-world investigation. The aim of this study was to evaluate the relationship between thyroid dysfunction and treatment using Food and Drug Administration (FDA)-approved VEGFR-TKIs. METHODS: Four data-mining algorithms were employed to detect thyroid dysfunction signals for VEGFR-TKIs, using data in the FDA Adverse Event Reporting System (FAERS) database from 68 quarters. MySQL Workbench and R were used to conduct statistical analysis. RESULTS AND DISCUSSION: We identified 32679 reports of thyroid dysfunction, of which 1567 listed VEGFR-TKIs as the primary suspected drugs. All four algorithms showed that the strength of the signals for hypothyroidism were greater than those for hyperthyroidism, for all the VEGFR-TKIs. In most cases, the median appearance time was within 100 days of initiation of VEGFR-TKIs therapy, except in the case of ponatinib. This indicated the need to actively identify and manage thyroid dysfunction during the early stages of VEGFR-TKIs treatment. WHAT IS NEW AND CONCLUSIONS: This study systematically identified the pharmacovigilance signals of thyroid dysfunction associated with the use of VEGFR-TKIs, using the FAERS database.

NADPH-cytochrome P450 reductase potentially involved in indoxacarb resistance in Spodoptera litura.

NADPH-cytochrome P450 reductase (CPR) plays a central role in the metabolism of insecticides. Numerous studies have shown that CPR is associated with insecticide resistance in insect. In this study, two transcripts of Spodoptera litura CPR (SlCPR-X1 and SlCPR-X2) were identified and cloned, and the deduced protein of SlCPR-X1 contains all the conserved CPR structural features (N-terminal membrane anchor, FMN, FAD and NADP binding domains, FAD binding motif, and catalytic residues). However, no N-terminal member anchor and a shorter FMN binding region have been identified in the deduced protein of SlCPR-X2. The specific expression patterns showed that SlCPR-X1 and SlCPR-X2 were detected in all tested developmental stages and tissues, but highly expressed in third-, fourth-, and fifth-instar larvae, and in midgut and fat body. In addition, compared with the susceptible strain, SlCPR-X1 and SlCPR-X2 were up-regulated and more inducible when treated with indoxacarb in the indoxacarb-resistant strain. However, the relative expression, up-regulation and induction of SlCPR-X1 were all higher than those of SlCPR-X2 in the indoxacarb-resistant strain. Furthermore, RNA interference and baculovirus expression system combined with MTT cytotoxicity assay demonstrated that only SlCPR-X1 with the N-terminal membrane anchor as the major CPR potentially involved in S. litura indoxacarb resistance. The outcome of this study further expands our understanding of the important role of insect CPR in xenobiotics detoxification and resistance development, and CPR could be a potential target for insecticide resistance management mediated by RNAi or CRISPR/Cas.

Transcription factor CncC potentially regulates the expression of multiple detoxification genes that mediate indoxacarb resistance in Spodoptera litura.

The xenobiotic transcription factor cap 'n' collar isoform C (CncC) is considered the central regulator of antioxidant and detoxification genes. Previous research indicated that CncC regulates three-phase enzymes responsible for insecticide resistance. In this study, the SlituCncC gene from Spodoptera litura was obtained and characterized. Quantitative polymerase chain reaction (qPCR) analysis showed that SlituCncC was expressed in all developmental stages and tissues, but was highly expressed in 3rd- and 4th-instar larvae, and in the Malpighian tubule, fat body, and midgut. In addition, SlituCncC was up-regulated and more highly induced with indoxacarb treatment in the indoxacarb-resistant strains compared with the susceptible strain. RNA interference-mediated gene silencing of SlituCncC significantly increased mortality of S. litura when exposed to indoxacarb. Furthermore, comparative transcriptome analysis showed that 842 genes were down-regulated and 127 genes were up-regulated in SlituCncC knockdown S. litura. Further analysis indicated that 18 three-phase enzymes were identified in the down-regulated genes, of which seven were associated with indoxacarb resistance in S. litura. qPCR analysis confirmed that expression of six of these seven genes was consistent with RNA sequencing data. All six detoxification genes were induced by indoxacarb, and the expression patterns were similar to that of SlituCncC. Finally, the CncC-Maf binding site was predicted in all six gene promoters. This study indicates that the transcription factor SlituCncC may regulate multiple detoxification genes that mediate indoxacarb resistance in S. litura.

Molecular characterization of a novel mitovirus from the plant­pathogenic fungus Botryosphaeria dothidea.

Here, a novel mycovirus, Botryosphaeria dothidea mitovirus 1 (BdMV1), was isolated from a phytopathogenic fungus, Botryosphaeria dothidea, and its molecular characteristics were determined. BdMV1 has a genome of 2,667 nt that contains a single large open reading frame (ORF) using the fungal mitochondrial genetic code. The ORF encodes an RNA-dependent RNA polymerase (RdRp) of 727 amino acids with a molecular mass of 81.64 kDa. BLASTp analysis revealed that the RdRp domain of BdMV1 has 39.59% and 39.18% sequence identity to Plasmopara viticola associated mitovirus 43 and Setosphaeria turcica mitovirus 1, respectively. Phylogenetic analysis further suggested that BdMV1 is a new member of the genus Mitovirus within the family Mitoviridae. To the best of our knowledge, this is the first report of a mitovirus in B. dothidea.