Metabolic Resistance of Sogatella furcifera (Hemiptera: Delphacidae) toward Pymetrozine Involves the Overexpression of CYP6FJ3.

Sogatella furcifera (Horváth), which mainly threatens rice, shows various levels of pesticide resistance due to long-term overuse of pesticides. Our resistance monitoring of 20 field populations in Sichuan, China, revealed that they were susceptible to highly resistant toward pymetrozine (0.4-142.2 RR), and JL21 reached the highest level of resistance. The JL21 population exhibited cross-resistance to triflumezopyrim and dinotefuran but sensitivity to sulfoxaflor, acetamiprid, clothianidin, and nitenpyram. The increased P450 activity were support to involve in pymetrozine resistance by detoxification enzyme activities and synergist determination. Among 16 candidate P450 genes, CYP6FJ3 (5.25-fold) was the most up-regulated in JL21, while no significant change was found after LC25 pymetrozine treatment. Furthermore, the knockdown by RNAi and heterologous overexpression by the GAL4/UAS system confirmed that the CYP6FJ3 overexpression was involved in the pymetrozine resistance, and recombination in vitro confirmed that CYP6FJ3 could hydroxylate pymetrozine. Therefore, the overexpression of CYP6FJ3 promotes pymetrozine metabolic resistance in S. furcifera.

Corrigendum: Effects of chlorantraniliprole on the life history traits of fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae).

[This corrects the article DOI: 10.3389/fphys.2023.1155455.].

Effects of chlorantraniliprole on the life history traits of fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae).

Introduction: Spodoptera frugiperda is an important nomadic agricultural pest with a diverse host range and resistance against several insecticides. The current study investigated the life history traits of two strains of the field-collected population against chlorantraniliprole using an age-stage two-sex life table. Method: For this, we established the chlorantraniliprole-susceptible (Crp-SUS G12), and chlorantraniliprole-reduced susceptible (Crp-RES G12) strains derived from the sixth generation of the QJ-20 population having a resistance ratio (RR) of 10.39-fold, compared with the reported susceptible population. Results: The results showed that the chlorantraniliprole-reduced susceptible strain attained a 4.0-fold RR, while the chlorantraniliprole-susceptible strain attained an RR of 0.85-fold, having overlapped fiducial limits (FLs) with the referred susceptible baseline. Meanwhile, the present study revealed that the development time of the susceptible strain was significantly longer than that of the reduced susceptible strain. Similarly, the mean longevity, adult pre-oviposition period (APOP), and total pre-oviposition period (TPOP) of the female chlorantraniliprole-susceptible strain were considerably longer than those of the female chlorantraniliprole-reduced susceptible strain. Contrarily, the population parameters, including the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R), of the chlorantraniliprole-susceptible strain were considerably lower than those of the chlorantraniliprole-reduced susceptible strain, while the mean generation time (T) of the chlorantraniliprole-susceptible strain was substantially longer than the chlorantraniliprole-reduced susceptible strain. The age-stage characteristic survival rate (s xj ) and age-stage characteristic life expectancy (e xj ) of the chlorantraniliprole-susceptible strain were longer than those of the chlorantraniliprole-reduced susceptible strain, but the age-stage-specific reproductive value (v xj ) of the chlorantraniliprole-susceptible strain was shorter than that of the chlorantraniliprole-reduced susceptible strain. Moreover, the contents of vitellogenin (Vg) and VgR in the chlorantraniliprole-reduced susceptible strain were higher than those in the chlorantraniliprole-susceptible strain. Discussion: These findings showed that reducing susceptibility to chlorantraniliprole promoted population growth in S. frugiperda. Therefore, this study could provide conceptual support for the integrated pest management (IPM) approach to control S. frugiperda in the field.

Reproductive Outbreaks of Sogatella furcifera Mediated by Overexpression of the Nuclear Receptor USP under Pressure from Triflumezopyrim.

Long-term pesticide-driven selection pressure is one of the main causes of insect outbreaks. In this study, we found that low doses of triflumezopyrim could increase the fecundity of white-backed planthoppers (Sogatella furcifera). By continuously screening 20 generations with a low dose of triflumezopyrim, a triflumezopyrim-resistant strain (Tri-strain, resistance ratio = 20.9-fold) was obtained. The average oviposition quantity and longevity of the Tri-strain (208.77 eggs and 21.31 days, respectively) were significantly higher than those of the susceptible strain (Sus-strain) (164.62 eggs and 17.85 days, respectively). To better understand the mechanism underlying the effects on reproduction, we detected the expression levels of several reproduction-related transcription factors in both the Tri- and Sus-strains. Ultraspiracle (USP) was significantly overexpressed in the Tri-strain. Knockdown of USP by RNAi severely inhibited the moulting process of S. furcifera and disrupted the development of female adult ovaries. Among the potential downstream target genes of USP, Kr-h1 (0.19-fold), Cht8 (0.56-fold) and GPCR A22 (0.31-fold) showed downregulated expression after USP-RNAi. In contrast, the expression of EcR (2.55-fold), which forms heterodimers with USP, was significantly upregulated. Furthermore, RNAi was performed on Kr-h1 in the Tri-strain, and the results show that larval moulting and the development of female adult ovaries were inhibited, consistent with the USP-RNAi results in S. furcifera. These results suggest that the transcription factors USP and Kr-h1 play important roles in the reproductive development of S. furcifera, and overexpression of USP and Kr-h1 in the Tri-resistant strain may result in reproductive outbreaks of pests.

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.

Diagnosis of Early Cervical Cancer with a Multimodal Magnetic Resonance Image under the Artificial Intelligence Algorithm.

This research was conducted to explore the value of multimodal magnetic resonance imaging (MRI) based on the alternating direction algorithm in the diagnosis of early cervical cancer. 64 patients diagnosed with early cervical cancer clinicopathologically were included, and according to the examination methods, they were divided into A group with conventional multimodal MRI examination and B group with the multimodal MRI examination under the alternating direction algorithm. The diagnostic results of two types of multimodal MRI for early cervical cancer staging were compared with the results of clinicopathological examination to judge the application value in the early diagnosis of cervical cancer. The results showed that in the 6 randomly selected samples of early cervical cancer patients, the peak signal-to-noise ratio (PSNR) and structural similarity image measurement (SSIM) of multimodal MRI images under the alternating direction algorithm were significantly higher than those of conventional multimodal MRI images and the image reconstruction was clearer under this algorithm. By comparing MRI multimodal staging, statistical analysis showed that the staging accuracy of B group was 75%, while that of A group was only 59.38%. For the results of postoperative medical examinations, the examination consistency of B group was better than that of A group, with a statistically significant difference (P < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of B group was larger than that of A group; thus, sensitivity was improved and misdiagnosis was reduced significantly. Multimodal MRI under the alternating direction algorithm was superior to conventional multimodal MRI examination in the diagnosis of early cervical cancer, as the lesions were displayed more clearly, which was conducive to the detection rate of small lesions and the staging accuracy. Therefore, it could be used as an ideal MRI method for the assistant diagnosis of cervical cancer staging.

Risk assessment and resistance inheritance of triflumezopyrim resistance in Laodelphax striatellus.

BACKGROUND: Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae) is one of the most important insect pests of rice, and it has been able to develop strong resistance to many insecticides. Triflumezopyrim, a new type of mesoionic insecticide developed by Corteva Agriscience, showed high biological activity in controlling piercing-sucking insect pests such as planthopper and leafhopper. RESULTS: In this study, we continuously selected a susceptible laboratory stain (Unsel) of L. striatellus for 16 generations by exposing it to triflumezopyrim in the laboratory. A 45.1-fold triflumezopyrim-resistant strain (Tri-sel) was established, in which cross-resistance to nitenpyram and acetamiprid was not detected. The realized heritability (h2 ) of the Tri-sel strain was estimated at 0.13. The mortalities of the testing F1 (the offspring of a cross between Unsel and Tri-sel strains) suggested that the resistance of L. striatellus to triflumezopyrim was autosomal and incompletely dominant, as well as a polygenic inheritance. In addition, the results of synergist experiment showed that P450s potentially contributed to the triflumezopyrim resistance. The activities of detoxification enzymes in the Unsel and Tri-sel strains indicated that the activity of P450s in the Tri-sel strain was significantly increased, consistent with the results of synergist experiments. Furthermore, 12 P450 genes demonstrated significant up-regulation. CONCLUSIONS: L. striatellus has a certain risk of resistance to triflumezopyrim after continuous selection. Triflumezopyrim resistance did not result in cross-resistance to neonicotinoid insecticides. The up-regulation of multiple P450 genes may mediate triflumezopyrim resistance in L. striatellus. © 2022 Society of Chemical Industry.

Irisin Activates M1 Macrophage and Suppresses Th2-Type Immune Response in Rats with Pelvic Inflammatory Disease.

OBJECTIVE: To investigate the mechanism of irisin to treat rats with acute pelvic inflammatory disease (APID). METHODS: Female rats were established as APID. Firstly, the content of IL-6, IL-8, TNF-α, and NF-kB was tested in rats' serum by enzyme linked immunosorbent assay (ELISA). Interferon-γ (IFN-γ) and IL-4 in the supernatant of pelvic homogenates were also detected. The mRNA expression of the inducible nitric oxide synthase (iNOS), TNF-α, chemokine ligand 1 (CXCL1), arginase-1(Arg1), and chitinase-3-like-3 (Chi313) genes in the pelvic cavity was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). IFN-γ and IL-4 secreted by spleen CD4+T cells and CD8+T cells were counted by flow cytometry, and the ratio of IFN-γ/IL-4 in CD4+T cells and CD8+T cells in the spleen was also detected by flow cytometry. RESULTS: Irisin reduced the levels of IL-6, IL-8, TNF-α, and NF-kB in serum. Compared with the APID group, the expression level of IL-4 in the APID + Irisin group was reduced in the homogenate. At the same time, Irisin promotes the activation of M1 macrophages in the uterus, ovaries, and uterine tubes of rats with APID. Irisin also inhibited Th2-type immune response. CONCLUSIONS: Irisin activates M1 macrophage and suppresses Th2-type immune response in APID rats.

Dysregulation of KIF14 regulates the cell cycle and predicts poor prognosis in cervical cancer: a study based on integrated approaches.

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.

The fitness advantages of bistrifluron resistance related to chitin synthase A in Spodoptera litura (Fab.) (Noctuidae: Lepidoptera).

BACKGROUND: Spodoptera litura is one of the major agricultural pests in China, and it has developed serious resistance to many traditional chemical insecticides. In the present study, the bistrifluron-resistant (Bis-SEL) strain accompanied by a higher oviposition, 113.8-fold RR compared to the bistrifluron-susceptible (Bis-UNSEL) strain, was obtained by bidirectional screening. A comparison of their gonad coefficiency and genes related to oviposition or resistance was used to elucidate the resurgence mechanism. RESULTS: The ovarian index, oviposition, and potential egg production in the Bis-SEL strain of female adults were significantly higher than those in the Bis-UNSEL strain, and the length of ovariole in the Bis-SEL strain was also significantly elongated. The protein contents of vitellogenin (Vg) and vitellogenin receptor (VgR) in the Bis-UNSEL strain were lower than those in the Bis-SEL strain, consistent with their gene expressions levels, and there was a significantly positive linear correlation between Vg and VgR protein contents, further confirming that resistant strains have high reproductive fitness. Moreover, the chitin synthase A in the Bis-SEL strain was clearly up-regulated, and a mutation (H866Y) near the QRRRW in the catalytic domain caused a rise in the hydrogen bond between UDP-GlcNAc and chitin synthase, and its chitin content was higher than that in the Bis-UNSEL strain. Nevertheless, the sensitivity of the Bis-SEL strain to bistrifluron was significantly recovered when it was knocked down though RNA interference. CONCLUSION: The fitness advantages of bistrifluron resistance may be related to the up-regulation and mution of chitin synthase A. © 2021 Society of Chemical Industry.

Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I-II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III-IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.

Characterization of genomic alterations in Chinese colorectal cancer patients.

OBJECTIVE: Colorectal cancer is one of the most prevalent types of cancer worldwide. Right-sided and left-sided colorectal cancer (RCC and LCC) patients respond differently to treatment. We aimed to identify the different mutational profile between RCC and LCC and provided evidence for future precision therapy. METHODS: A total of 630 Chinese colorectal cancer patients, including 467 (74.1%) LCC and 163 (25.9%) RCC, were enrolled in this cohort. Both formalin-fixed paraffin-embedded tumor tissues and matching blood samples were collected and deep sequenced targeting 450 cancer genes for genomic alteration analysis. Tumor mutational burden was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most common mutated genes were TP53 (77.0%), APC (71.7%), KRAS (50.0%), SMAD4 (19.8%), PIK3CA (18.3%), FBXW7 (17.5%), TCF7L2 (12.5%), SOX9 (11.3%), LRP1B (10.8%), ARID1A (10.3%) and FAT4 (10.3%). The mutation frequencies of TP53 and APC in LCC were significantly higher than that of RCC, while the mutation frequency of PIK3CA was lower than that of RCC. Six gene fusions were specifically detected in RCC patients. Colorectal cancer sites were associated with gender (P = 4.15 × 10-5) and tumor differentiation (P = 0.059). In LCC, the gender-associated genes were FAT4, EP300, FAT1, LRP1, ARID1B, AR, FYN and TAF1, while in RCC, they were ARID1A, SMARCA4, LRP1 and GRIN2A. The mutations of 18 genes were associated with tumor differentiation (8 for LCC and 10 for RCC). High tumor mutational burden was more common in RCC. Our results implied more potential targeted drug therapy opportunities for RCC. CONCLUSION: We describe the different molecular characteristics of LCC and RCC. Our result supported a better prognosis of RCC than LCC in Chinese colorectal cancer patients.

Dysregulation of KIF14 regulates the cell cycle and predicts poor prognosis in cervical cancer: a study based on integrated approaches

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.

Characteristics of genomic alterations in Chinese cholangiocarcinoma patients.

OBJECTIVE: Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. METHODS: The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55-65 years old. BAP1 and LRP2 mutations were associated with TMB. CONCLUSIONS: Most Chinese CCA patients were 50-70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.

Sublethal Effects of Triflumezopyrim on Biological Traits and Detoxification Enzyme Activities in the Small Brown Planthopper Laodelphax striatellus (Hemiptera: Delphacidae).

The small brown planthopper [Laodelphax striatellus (Fallén) (Hemiptera, Delphacidae)] is one of the most destructive insect pests of rice and has developed strong resistance to several kinds of chemical insecticides. Triflumezopyrim, a novel mesoionic insecticide developed by Corteva Agriscience (formerly DuPont Crop Protection), has efficient biological activity in controlling sucking insects, such as the planthopper. However, the effects of triflumezopyrim on the growth and reproduction of L. striatellus have not been reported. In this study, an F5 generation was obtained by conducting five rounds of insecticide screening on a sensitive L. striatellus strain (F0 generation). An age-stage life table procedure was used to evaluate the effects of a sublethal concentration (LC50) of triflumezopyrim on the biological parameters of L. striatellus. Compared with those of the F0 generation, the intrinsic rate of increase (r), the finite rate (λ), and the net reproductive rate (R 0) of the F5 generation were significantly decreased; nevertheless, the average duration of life (T) was not significantly affected. The results of detoxification enzyme activity assays indicated that the glutathione S-transferase and cytochrome P450 monooxygenase (P450) activities in the F5 generation were significantly higher than those in the F0 generation. The contents of vitellogenin (Vg) and vitellogenin receptor (VgR) were also detected, and the results indicated that the contents of Vg and VgR in the F5 generation were significantly decreased compared to those in the F0 generation. Furthermore, we detected the relative expression of ecdysone receptor (EcR), Vg, and VgR in the F0 and F5 generations and found that the relative expression levels of Vg and VgR in the F5 generation female adults were obviously lower than those in the F0 generation (P < 0.05), whereas the relative expression of EcR was slightly increased, although the difference was not significant (P > 0.05). Based on these results, a sublethal concentration (median lethal concentration, LC50) of triflumezopyrim may inhibit the generational growth and reproduction of L. striatellus. Moreover, our results may provide a reference for further studies of the suitability and resistance mechanisms of L. striatellus subjected to a sublethal dose of triflumezopyrim.

Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non­small cell lung cancer.

Lung cancer is the most prevalent cancer worldwide and non­small cell lung cancer (NSCLC) is the most common subtype and accounts for 75% of all lung cancer cases. Although programmed death­1/programmed death­ligand­1 (PD­1/PD­L1) blockade has shown good results in the clinic, numerous NSCLC patients still fail to respond to this therapy. In the current study, formalin­fixed, paraffin­embedded tumor and matched blood samples from 1,984 Chinese NSCLS patients were collected for detection of genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations and gene rearrangements. The most common mutated genes were tumor protein p53 (55.70%; 1,105/1,984), epidermal growth factor receptor (52.47%; 1,041/1,184), KRAS proto­oncogene GTPase (13.36%, 265/1084), cyclin dependent kinase inhibitor 2A (12.30%; 244/1,984), LDL receptor related protein 1B (11.09%; 220/1,984) and telomerase reverse transcriptase (10.58%; 210/1,984). Tumor mutational burden was calculated and results revealed that it was associated with PI3K/mTOR pathway gene mutations, and patient's gender, age, smoking status, and tumor stage. In addition, mutations of phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit α or F­box and WD repeat domain containing 7 were detected in 3 patients with NSCLC who were resistant to PD­1 inhibitors nivolumab and pembrolizumab. Disease stabilization and tumor shrinkage were observed in these patients after mTOR inhibitor everolimus treatment. The current data showed that NSCLC with PI3K/mTOR mutations are sensitive to mTOR inhibitors.

Comprehensive genomic profile of cholangiocarcinomas in China.

Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as locally advanced or metastatic. Previous studies have revealed genomic characteristics of CCA in Western patients, however comprehensive genomic features of CCA in Chinese patients have not been well understood. To explore the specific genomic characteristics of Chinese patients with CCA, a total of 66 patients with CCA, including 44 intrahepatic CCA (iCCA) and 22 extrahepatic CCA (exCCA) cases, were studied. The most commonly altered genes in CCAs were TP53 (62.12%, 41/66), KRAS (36.36%, 24/66), SMAD4 (24.24%, 16/66), TERT (21.21%, 14/66), ARID1A (19.70%, 13/66), CDKN2A (19.70%, 13/66), KMT2C (9.09%, 6/66) and RBM10 (9.09%, 6/66), ERBB2 (7.58%, 5/66) and BRAF (7.58%, 5/66). Many gene mutations, including STK11, CCND1 and FGF19, were only found in iCCA. RBM10 mutations were found to be significantly higher in exCCA. The gene mutations of neurofibromin 1, STK11, CCND1 and FBXW7 specifically occurred in males, whereas gene mutations of ERBB2, AXIN2 and CREBBP specifically occurred in females. ERBB2 mutations were significantly associated with the sex of patients with CCA. Mutations in PIK3CA, FGFR2 and ZNF750 were significantly associated with the age of patients with CCA and TERT mutations were significantly associated with tumor differentiation. Alterations in KMT2C, PBRM1, AXIN2, MAGI2, BRCA2 and SPTA1 were associated with tumor mutational burden. The findings of the present study suggest that targeted sequencing, using next-generation sequencing technology, provides comprehensive and accurate information on genomic alterations, which will provide novel potential biomarkers for the diagnosis of CCA and may guide precise therapeutic strategies for Chinese patients with CCA.

The population growth, development and metabolic enzymes of the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae) under the sublethal dose of triflumezopyrim.

Triflumezopyrim, a new nicotinic acetylcholine receptor (nAChR) inhibition, can effectively control piercing-sucking insect pests such as white-backed planthopper (Sogatella furcifera). At present, there has been no reports on the effects of triflumezopyrim on the population growth and development of S. furcifera. In this experiment, an age-stage two-sex life table was used to evaluate the impact of triflumezopyrim on the biological parameters of S. furcifera. The results showed that the adult preoviposition period (APOP) and total preoviposition period (TPOP) of the F1 generation were significantly higher than those of the F0 and F4 generations, on the contrary the average fecundity, intrinsic rate of increase (r) and finite rate of increase (λ) of the F4 generation were higher than those of the F0 and F1 generations. The results of synergists and enzyme activities indicated that the CarE and P450 activities in the F4 generation were significantly higher than those in the F0 generation (P < 0.05). The protein contents of vitellogenin (Vg) and vitellogenin receptor (VgR) and relative expression quality of VgR in the F4 female adults were also significantly higher than those in the F0 generation (P < 0.05). These results showed that triflumezopyrim at a low concentration could promote the growth and reproduction of S. furcifera, and that may provide a reference for the rational use of triflumezopyrim in the future.