Gap junction protein connexin43 deregulation contributes to bladder carcinogenesis via targeting MAPK pathway.

High expression of connexins was found in a variety of cancers, but their role is still controversial. We investigated whether connexin43 (Cx43) contributed to bladder carcinogenesis through MAPK activation. In this study, we found that Cx43 expression was significantly increased in bladder cancer tissues and cell line. Overexpression of Cx43 in bladder cancer 5637 cells increased cell proliferation, promoted cell cycle progression, and inhibited apoptosis. Western blot showed that JNK and ERK pathways were dramatically activated in Cx43-overexpressed cells. Conversely, knockdown of Cx43 inhibited cell proliferation by increasing apoptosis and causing cell cycle arrest, concomitant with inhibition of JNK and ERK signaling. In addition, JNK and ERK pathways were also activated in bladder cancer tissues. In conclusion, abnormal high expression and cytoplasmic localization of Cx43 contributed to bladder cancer. Inhibition of Cx43 activity could be a potential therapeutic strategy for preventing the progression of bladder cancer.

MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma.

The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation by activation of the DNA repair machinery to preserve the cell, or by induction of apoptosis to eliminate the cell should the damage prove irrevocable. The gene encoding p53 frequently undergoes inactivating mutations in many human cancers, but WT p53 is often expressed at high levels in melanoma, which, as judged from the malignant nature of the disease, fails to act as an effective tumor suppressor. Here we show that p53 directly up-regulates microRNA-149* (miR-149*) that in turn targets glycogen synthase kinase-3α, resulting in increased expression of Mcl-1 and resistance to apoptosis in melanoma cells. Although deficiency in miR-149* undermined survival of melanoma cells and inhibited melanoma growth in a mouse xenograft model, elevated expression of miR-149* was found in fresh human metastatic melanoma isolates, which was associated with decreased glycogen synthase kinase-3α and increased Mcl-1. These results reveal a p53-dependent, miR-149*-mediated pathway that contributes to survival of melanoma cells, provides a rational explanation for the ineffectiveness of p53 to suppress melanoma, and identifies the expression of miR-149* as a mechanism involved in the increased expression of Mcl-1 in melanoma cells.

A chromosome-level genome for the flower thrips Frankliniella intonsa.

The flower thrips Frankliniella intonsa (Thysanoptera: Thripidae) is a common insect found in flowers of many plants. Sometimes, F. intonsa causes damage to crops through direct feeding and transmission of plant viruses. Here, we assembled a chromosomal level genome of F. intonsa using the Illumina, Oxford Nanopore (ONT), and Hi-C technologies. The assembled genome had a size of 209.09 Mb, with a contig N50 of 997 bp, scaffold N50 of 13.415 Mb, and BUSCO completeness of 92.5%. The assembled contigs were anchored on 15 chromosomes. A set of 14,109 protein-coding genes were annotated in the genome with a BUSCO completeness of 95.0%. The genome contained 491 non-coding RNA and 0.57% of interspersed repeats. This high-quality genome provides a valuable resource for understanding the ecology, genetics, and evolution of F. intonsa, as well as for controlling thrips pests.

A comprehensive assessment of insecticide resistance mutations in source and immigrant populations of the diamondback moth Plutella xylostella (L.).

BACKGROUND: The diamondback moth (DBM) Plutella xylostella has developed resistance to almost all insecticides used to control it. Populations of DBM in temperate regions mainly migrate from annual breeding areas. However, the distribution pattern of insecticide resistance of DBM within the context of long-distance migration remains unclear. RESULTS: In this study, we examined the frequency of 14 resistance mutations for 52 populations of DBM collected in 2010, 2011, 2017 and 2018 across China using a high-throughput KASP genotyping method. Mutations L1041F and T929I conferring pyrethroid resistance, and mutations G4946E and E1338D conferring chlorantraniliprole resistance were near fixation in most populations, whereas resistant alleles of F1020S, M918I, A309V and F1845Y were uncommon or absent in most populations. Resistance allele frequencies were relatively stable among different years, although the frequency of two mutations decreased. Principal component analysis based on resistant allele frequencies separated a southern population as an outlier, whereas the immigrants clustered with other populations, congruent with the migration pattern of northern immigrants coming from the Sichuan area of southwestern China. Most resistant mutations deviated from Hardy-Weinberg equilibrium due to a lower than expected frequency of heterozygotes. The deviation index of heterozygosity for resistant alleles was significantly higher than the index obtained from single nucleotide polymorphisms across the genome. These findings suggest heterogeneous selection pressures on resistant mutations. CONCLUSION: Our results provide a picture of resistant mutation patterns in DBM shaped by insecticide usage and migration of this pest, and highlight the widespread distribution of resistance alleles in DBM. © 2022 Society of Chemical Industry.

Interspecific and intraspecific variation in susceptibility of two co-occurring pest thrips, Frankliniella occidentalis and Thrips palmi, to nine insecticides.

BACKGROUND: Field control of pest thrips mainly relies on insecticides, but the toxicity of insecticides can vary among thrips species and populations. In this study, we examined the susceptibility of multiple field populations of two thrips pests, Frankliniella occidentalis, and Thrips palmi, that often co-occur on vegetables, to nine insecticides belonging to seven subgroups. RESULTS: The highest level of variation in susceptibility among F. occidentalis populations was for spinetoram (73.92 fold difference between most resistant and most susceptible population), followed by three neonicotinoids (8.06-15.99 fold), while among T. palmi populations, it was also for spinetoram (257.19 fold), followed by emamectin benzoate, sulfoxaflor, and acetamiprid (23.64-45.50 fold). These findings suggest evolved resistance to these insecticides in some populations of the two thrips. One population of F. occidentalis had a particularly high level of resistance overall, being the most resistant for five of the nine insecticides tested. Likewise, a population of T. palmi had high resistance to all nine insecticides, again suggesting the evolution of resistance to multiple chemicals. For F. occidentalis, the LC95 values of most populations were higher than the field-recommended dosage for all insecticides except chlorfenapyr and emamectin benzoate. For several T. palmi populations, the LC95 values also tended to be higher than recommended dosages, except in the case of emamectin benzoate and spinetoram. CONCLUSIONS: Our study found interspecific and intraspecific variations in the susceptibility of two thrips to nine insecticides and multiple resistance in some populations, highlighting the need for ongoing monitoring and resistance management. © 2023 Society of Chemical Industry.

Toxicity and Control Efficacy of an Organosilicone to the Two-Spotted Spider Mite Tetranychus urticae and Its Crop Hosts.

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.

Proton Magnetic Resonance Spectroscopy for Diagnosis of Non-Motor Symptoms in Parkinson's Disease.

Background: The current diagnosis of Parkinson's disease (PD) is mainly based on the typical clinical manifestations. However, 60% dopaminergic neurons have died when the typical clinical manifestations occur. Predictive neurobiomarkers may help identify those PD patients having non-motor disorders or in different stage and achieving the aim of early diagnosis. Up to date, few if any neuroimaging techniques have been described useful for non-movement disorders diagnosis in PD patients. Here, we investigated the alteration of metabolites in PD patients in different stage of PD and non-motor symptoms including sleep, gastrointestinal and cognitive dysfunction, by using the 1H-MRS. Methods: A total of 48 subjects were included between 2017 and 2019: 37 PD (15 men, age 47-82 years) and 11 healthy people (8 men, age 49-74 years). All participants underwent MRI and multi-voxel 1H-MRS examination within 3 days in admission. Six kinds of metabolites, such as creatine (Cr), N-acetyl aspartate/creatine (NAA/Cr), N-acetyl aspartate/choline (NAA/Cho), choline/creatine (Cho/Cr), lipid/creatine (LL/Cr), and myo-Inositol/creatine ratio (mI/Cr) were tested among the PD group and the control groups. Statistical analyses and correlation analyses were performed by using SPSS. The p < 0.05 was considered statistically significant. Results: Compared late PD group with a control group or early group, higher Cr ratio and lower NAA/Cr ratio were observed in the late PD group (p < 0.05). The mI/Cr in the late PD group was also lower than that in the early PD group (p < 0.05). Regarding the relationship between metabolites and NMS, Cho/Cr was higher in the sleep disorder group, whereas mI/Cr was lower in the gastrointestinal dysfunction group in comparison with the non-symptom groups. Moreover, Cr, Cho/Cr, mI/Cr, and LL/Cr were identified to have higher concentrations in the cognitive group in thalamus. Conclusions: Proton magnetic resonance spectroscopy is an advanced tool to quantify the metabolic changes in PD. Three biomarkers (Cr, NAA/Cr, and mI/Cr) were detected in the late stage of PD, suggesting that these markers might be potential to imply the progression of PD. In addition, subgroups analysis showed that MRS of thalamus is a sensitive region for the detection of cognitive decline in PD, and the alteration of neurochemicals (involving Cr, Cho, mI, and LL) may be promising biomarkers to predict cognitive decline in PD.

Variation in the toxicity of a novel meta-diamide insecticide, broflanilide, among thrips pest species and developmental stages.

BACKGROUND: Thrips pests cause increasing damage to crops around the world. Widespread usage of some insecticides against thrips has now led to the evolution of resistance to several active ingredients, and new insecticides are required. This study examined the toxicity of the novel insecticide broflanilide to multiple populations of several thrips pests. RESULTS: Bioassays showed that thrips populations had LC50 values ranging from 0.5 to almost 300 mg·L-1 . A population of Frankliniella occidentalis had the highest LC50 value at 290.63 mg·L-1 , while a population of Echinothrips americanus had the lowest LC50 value at 0.51 mg L-1 . LC50 values among seven populations of Thrips palmi ranged from 2.5689 to 23.6754 mg·L-1 , indicating intraspecific variation in toxicity. In this species, the toxicity of broflanilide was relatively higher in adults than in larvae. More than 90% of eggs of T. palmi could not develop into larvae when treated with 5-50 mg L-1 broflanilide. Compared to five commonly used insecticides, broflanilide showed relatively high toxicity to T. palmi. Field control tests with T. palmi showed that control efficacy (from 90.44% to 93.14%) was maintained from day three to day 14 after treatment with 22.5 and 45 ga.i hm-1 broflanilide. CONCLUSION: Broflanilide is potentially a useful insecticide for controlling Thrips hawaiiensis, Frankliniella intonsa, Megalurothrips usitatus. E. americanus, and some populations of T. palmi. However, the variation in toxicity of this insecticide to different species, populations, and developmental stages indicates that target species and life stages may need to be carefully considered. © 2022 Society of Chemical Industry.

Construction of a prognostic immune signature for lower grade glioma that can be recognized by MRI radiomics features to predict survival in LGG patients.

BACKGROUND: This study aimed to identify a series of prognostically relevant immune features by immunophenoscore. Immune features were explored using MRI radiomics features to prediction the overall survival (OS) of lower-grade glioma (LGG) patients and their response to immune checkpoints. METHOD: LGG data were retrieved from TCGA and categorized into training and internal validation datasets. Patients attending the First Affiliated Hospital of Harbin Medical University were included in an external validation cohort. An immunophenoscore-based signature was built to predict malignant potential and response to immune checkpoint inhibitors in LGG patients. In addition, a deep learning neural network prediction model was built for validation of the immunophenoscore-based signature. RESULTS: Immunophenotype-associated mRNA signatures (IMriskScore) for outcome prediction and ICB therapeutic effects in LGG patients were constructed. Deep learning of neural networks based on radiomics showed that MRI radiomic features determined IMriskScore. Enrichment analysis and ssGSEA correlation analysis were performed. Mutations in CIC significantly improved the prognosis of patients in the high IMriskScore group. Therefore, CIC is a potential therapeutic target for patients in the high IMriskScore group. Moreover, IMriskScore is an independent risk factor that can be used clinically to predict LGG patient outcomes. CONCLUSIONS: The IMriskScore model consisting of a sets of biomarkers, can independently predict the prognosis of LGG patients and provides a basis for the development of personalized immunotherapy strategies. In addition, IMriskScore features were predicted by MRI radiomics using a deep learning approach using neural networks. Therefore, they can be used for the prognosis of LGG patients.

Determination of isoform-specific RNA structure with nanopore long reads.

Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. We show that shared sequences in different transcript isoforms of the same gene can fold into different structures, highlighting the importance of long-read sequencing for obtaining phase information. We also demonstrate that structural differences between transcript isoforms of the same gene lead to differences in translation efficiency. By revealing isoform-specific RNA structure, PORE-cupine will deepen understanding of the role of structures in controlling gene regulation.