Crizotinib inhibits the metabolism of tramadol by non-competitive suppressing the activities of CYP2D1 and CYP3A2.

Objectives: To investigate the interaction between tramadol and representative tyrosine kinase inhibitors, and to study the inhibition mode of drug-interaction. Methods: Liver microsomal catalyzing assay was developed. Sprague-Dawley rats were administrated tramadol with or without selected tyrosine kinase inhibitors. Samples were prepared and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for analysis. Besides, liver, kidney, and small intestine were collected and morphology was examined by hematoxyline-eosin (H&E) staining. Meanwhile, liver microsomes were prepared and carbon monoxide differential ultraviolet radiation (UV) spectrophotometric quantification was performed. Results: Among the screened inhibitors, crizotinib takes the highest potency in suppressing the metabolism of tramadol in rat/human liver microsome, following non-competitive inhibitory mechanism. In vivo, when crizotinib was co-administered, the AUC value of tramadol increased compared with the control group. Besides, no obvious pathological changes were observed, including cell morphology, size, arrangement, nuclear morphology with the levels of alanine transaminase (ALT) and aspartate transaminase (AST) increased after multiple administration of crizotinib. Meanwhile, the activities of CYP2D1 and CYP3A2 as well as the total cytochrome P450 abundance were found to be decreased in rat liver of combinational group. Conclusions: Crizotinib can inhibit the metabolism of tramadol. Therefore, this recipe should be vigilant to prevent adverse reactions.

Sonosynthetic Cyanobacteria Oxygenation for Self-Enhanced Tumor-Specific Treatment.

Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well-known low penetration depth of external light. Here, ultrasound-mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound-induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof-of-concept sonosynthesis (sonoafterglow-induced photosynthesis) in cancer therapy. Chlorin e6, a typical small-molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue-penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia-inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.

Calcium Hexacyanoferrate Nanozyme Enhances Plant Stress Resistance by Oxidative Stress Alleviation and Heavy Metal Removal.

Oxidative damage, exacerbated by the excessive accumulation of reactive oxygen species (ROS), profoundly inhibits both crop growth and yield. Herein, a biocompatible nanozyme, calcium hexacyanoferrate nanoparticles (CaHCF NPs), targeting ROS is developed, to mitigate oxidative damage and sequestrate heavy metal ions during plant growth. Uniquely, CaHCF NPs feature multifaced enzyme-like activities, involving superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase, thiol peroxidase, and ascorbate peroxidase, which enable them to neutralize excessive ROS. Furthermore, CaHCF NPs promote calcium-cadmium exchange process, diminishing the uptake of heavy metals. Importantly, 120 µg mL-1 of CaHCF NPs alleviate the inhibitory effects of hydrogen peroxide and cadmium chloride on Arabidopsis and tomato. The activities of SOD, POD, and CAT increase by 46.2%, 74.4%, and 48.3%, respectively, meanwhile the glutathione level rises by 72.4% in Arabidopsis under cadmium stress. Moreover, CaHCF NPs boost the expression of genes associated with antioxidation, heavy metal detoxification, nutrient transport, and stress resistance. These findings unveil the significant potential of nanoplatforms equipped with nanozymes in alleviating oxidative stress in plants, which not only regulate crop growth but also substantially ameliorate yield and quality, heralding a new era in agricultural nanotechnology.

Appropriate induction of TOC1 ensures optimal MYB44 expression in ABA signaling and stress response in Arabidopsis.

Plants possess the remarkable ability to integrate the circadian clock with various signalling pathways, enabling them to quickly detect and react to both external and internal stress signals. However, the interplay between the circadian clock and biological processes in orchestrating responses to environmental stresses remains poorly understood. TOC1, a core component of the plant circadian clock, plays a vital role in maintaining circadian rhythmicity and participating in plant defences. Here, our study reveals a direct interaction between TOC1 and the promoter region of MYB44, a key gene involved in plant defence. TOC1 rhythmically represses MYB44 expression, thereby ensuring elevated MYB44 expression at dawn to help the plant in coping with lowest temperatures during diurnal cycles. Additionally, both TOC1 and MYB44 can be induced by cold stress in an Abscisic acid (ABA)-dependent and independent manner. TOC1 demonstrates a rapid induction in response to lower temperatures compared to ABA treatment, suggesting timely flexible regulation of TOC1-MYB44 regulatory module by the circadian clock in ensuring a proper response to diverse stresses and maintaining a balance between normal physiological processes and energy-consuming stress responses. Our study elucidates the role of TOC1 in effectively modulating expression of MYB44, providing insights into the regulatory network connecting the circadian clock, ABA signalling, and stress-responsive genes.

[Water-soluble Inorganic Ion Content of PM2.5 and Its Change Characteristics in Urban Area of Beijing in 2022].

To explore the content and variation characteristics of water-soluble ions of atmospheric fine particles (PM2.5) in a Beijing urban area and put forward the pollution prevention and control scheme, the water-soluble ions, gaseous precursors (SO2, NO2), and meteorological factors (temperature, RH) of PM2.5 in 2022 were analyzed and determined. The results showed that the water-soluble ions with the highest proportion in PM2.5 in the Beijing City urban area were NO3-, NH4+, and SO42-, accounting for 52.7% of PM2.5. The mass concentrations of PM2.5 and SNA were lower than the historical results, whereas the proportion of SNA, SOR, and NOR was higher than the historical results. This showed that the fine particulate matter pollution in Beijing has been significantly improved, but it still has strong secondary pollution characteristics. NO3-/SO42-(2.2) was higher than those of historical and nearby provinces and cities, reflecting the expanding influence of mobile sources. In terms of seasonal variation, PM2.5 showed the characteristic of high in autumn and low in summer. The proportion of NO3- was the highest in autumn, spring, and winter; the proportion of SO42- was the highest in summer; and the proportion of NH4+ changed little in each season. The seasonal variation rules of NOR and SOR were almost opposite, which reflected the difference in transformation factors between NOR and SOR. The main forms of SNA in the Beijing urban area were NH4NO3 and (NH4)2SO4. The neutralization degree of cations and anions was the highest in winter, the cation NH4+ was slightly insufficient in summer, and NH4+ was in excess in spring and autumn. The Beijing urban area was an ammonia-rich environment. In terms of pollution level, RH, particulate matter moisture, and water-soluble ions mass concentration all increased with the increase in pollution level, and SNA increased fastest, with its proportion in PM2.5 increasing first and then stabilizing, whereas the contribution rate of other water-soluble ions decreased gradually. In terms of spatial distribution, the mass concentration relationship of SNA at the central urban area and suburbs was NO3- > SO42- > NH4+, which reflected the pollution characteristics dominated by NO3-. The highest contribution rate of SNA to PM2.5 occurred in the eastern region, the central urban area, and the transmission point, indicating that the secondary reaction was relatively active in the central urban area and the eastern region, and the regional transport was also an important source of secondary ions.

The global, regional, and national burden of stomach cancer attributed to smoking in 204 countries, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

INTRODUCTION: Understanding the current burden of stomach cancer linked to smoking and the variations in trends across different locations, is crucial for developing effective prevention strategies. In this study, we present findings on the age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate attributed to smoking in 204 countries and territories spanning 21 regions from 1990 to 2019. METHODS: The data for this study were obtained from the Global Burden of Disease Study (GBD) 2019, which assessed 369 diseases and injuries, as well as 87 risk factors in 204 countries and 21 regions. To assess the trend in ASDR and age-standardized DALYs rate, the estimated annual percentage change (EAPC) was utilized. RESULTS: Between 1990 and 2019, smoking was found to be associated with a decrease in ASDR (EAPC = -2.20) and age-standardized DALYs (EAPC = -2.42) rates for gastric cancer. As the sociodemographic index (SDI) increased, the decline in rates also increased gradually. However, the decline was smallest in regions with low SDI (EAPCASDR = -1.34; EAPCage-standardized DALYs rate = -1.38). In 21 regions, both ASDR and DALYs rates experienced a decline. The smallest decline in ASDR was observed in Western Sub-Saharan Africa, with an EAPC of -0.80, while the smallest decline in DALYs rate was found in Oceania, with an EAPC of -0.81. Among the 204 countries analyzed, the Dominican Republic showed the highest increase in ASDR and age-standardized DALYs rate (EAPCASDR = 1.19; EAPCage-standardized DALYs rate = 1.21), followed by Afghanistan (EAPCASDR = 1.09; EAPCage-standardized DALYs rate = 1.09) and Sao Tome and Principe (EAPCASDR = 1.05; EAPCage-standardized DALYs rate = 1.03). In the year 2019, the highest ASDR and age-standardized DALYs rate was observed in East Asia, with the highest rates occurring in Mongolia. CONCLUSIONS: The burden of stomach cancer worldwide, adjusted for age, and related to smoking, has shown a decline from 1990 to 2019. However, regional disparities have been identified, with some areas experiencing an increase in this burden. These regions with a higher burden emphasize the necessity for the implementation of strong tobacco control measures.

Chromosome-level genome assembly of the Japanese sawyer beetle Monochamus alternatus.

The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors.

Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect.

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Selection and validation of optimal reference genes for RT-qPCR analyses in Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae).

Aphidoletes aphidimyza is a predator that is an important biological agent used to control agricultural and forestry aphids. Although many studies have investigated its biological and ecological characteristics, few molecular studies have been reported. The current study was performed to identify suitable reference genes to facilitate future gene expression and function analyses via quantitative reverse transcription PCR. Eight reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RPS13, RPL8, RPS3, α-Tub, ß-actin, RPL32, and elongation factor 1 alpha (EF1-α) were selected. Their expression levels were determined under four different experimental conditions (developmental stages, adult tissues, sugar treatment, and starvation treatment) using qRT-PCR technology. The stability was evaluated with five methods (Ct value, geNorm, NormFinder, BestKeeper, and RefFinder). The results showed that GAPDH, RPL32, and EF1-α were ranked as the best reference gene combinations for measuring gene expression levels among different developing stages and in various starvation treatments. RPL8 and RPS3 were recommended to normalize the gene expression levels among different adult tissues. RPL32, ß-actin, and EF1-α were recommended sugar-feeding conditions. To validate the utility of the selected reference pair, RPL8, and RPS3, we estimated the tissue-biased expression level of a chemosensory protein gene (AaphCSP1). As expected, AaphCSP1 is highly expressed in the antennae and lowly expressed in the abdomen. These findings will lay the foundation for future research on the molecular physiology and biochemistry of A. aphidimyza.

Testing for adaptive changes linked to range expansion following a single introduction of the fall webworm.

Adaptive evolution following colonization can affect the impact of invasive species. The fall webworm (FWW) invaded China 40 years ago through a single introduction event involving a severe bottleneck and subsequently diverged into two genetic groups. The well-recorded invasion history of FWW, coupled with a clear pattern of genetic divergence, provides an opportunity to investigate whether there is any sign of adaptive evolution following the invasion. Based on genome-wide SNPs, we identified genetically separated western and eastern groups of FWW and correlated spatial variation in SNPs with geographical and climatic factors. Geographical factors explained a similar proportion of the genetic variation across all populations compared with climatic factors. However, when the two population groups were analysed separately, environmental factors explained more variation than geographical factors. SNP outliers in populations of the western group had relatively stronger response to precipitation than temperature-related variables. Functional annotation of SNP outliers identified genes associated with insect cuticle protein potentially related to desiccation adaptation in the western group and genes associated with lipase biosynthesis potentially related to temperature adaptation in the eastern group. Our study suggests that invasive species may maintain the evolutionary potential to adapt to heterogeneous environments despite a single invasion event. The molecular data suggest that quantitative trait comparisons across environments would be worthwhile.

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.

A high-throughput KASP assay provides insights into the evolution of multiple resistant mutations in populations of the two-spotted spider mite Tetranychus urticae across China.

BACKGROUND: The two-spotted spider mite (TSSM), Tetranychus urticae (Acari: Tetranychidae), is a cosmopolitan phytophagous pest in agriculture and horticulture. It has developed resistance to many acaricides by target-site mutations. Understanding the status and evolution of resistant mutations in the field is essential for resistance management. Here, we applied a high-throughput Kompetitive allele-specific polymerase chain reaction (KASP) method for detecting six mutations conferring resistance to four acaricides of the TSSM. We genotyped 3274 female adults of TSSM from 43 populations collected across China in 2017, 2020, and 2021. RESULTS: The KASP genotyping of 24 testing individuals showed 99% agreement with Sanger sequencing results. KASP assays showed that most populations had a high frequency of mutations conferring avermectin (G314D and G326E) and pyridaben (H92R) resistance. The frequency of mutation conferring bifenazate (A269V and G126S) and etoxazole (I1017F) resistance was relatively low. Multiple mutations were common in the TSSM, with 70.2% and 24.6% of individuals having 2-6 and 7-10 of 10 possible resistant alleles, respectively. No loci were linked in most populations among the six mutations, indicating the development of multiple resistance is mainly by independent selection. However, G314D and I1017F on the nuclear genome deviated from Hardy-Weinberg equilibrium in most populations, indicating significant selective pressure on TSSM populations by acaricides or fitness cost of the mutations in the absence of acaricide selection. CONCLUSION: Our study revealed that the high frequency of TSSMs evolved multiple resistant mutations in population and individual levels by independent selection across China, alarming for managing multiple-acaricides resistance. © 2023 Society of Chemical Industry.

KASP genotyping and semi-quantitation of G275E mutation in the α6 subunit of Thrips palmi nAChR gene conferring spinetoram resistance.

BACKGROUND: Pesticide resistance is a long-standing and growing problem in the chemical control of invertebrate pests. Molecular diagnostic methods can facilitate pesticide resistance management by accurately and efficiently detecting resistant mutations and their frequency. In this study, the kompetitive allele specific PCR (KASP) approach, a technology for high-throughput single nucleotide polymorphism (SNP) genotyping, is validated as a useful method for characterizing genotypes at a pesticide-resistance locus for the first time. We focus on the spinetoram resistance mutation of G275E in the nicotinic acetylcholine receptor alpha 6 (nAChR α6) subunit gene of Thrips palmi. RESULTS: Of the 341 individuals of Thrips palmi tested, 98.24% were successfully genotyped, with 100% concordance with Sanger sequencing results. We then quantitatively mixed genomic DNA of known genotypes to establish 21 DNA mixtures with a resistant allele frequency ranging from 0 to 100% at steps of 5%. The linear discriminant analysis (LDA) showed that 75.8% of original grouped cases were correctly classified; six groups had no overlap in membership (resistant allele frequency: 0%, 5%, 10-75%, 80-85%, 90-95%, and 100%). When we chose 11 pooled samples with 10% steps for LDA, 84.4% of original grouped cases were correctly classified; seven groups had no overlap in membership (0%, 10%, 20-30%, 40-70%, 80%, 90%, 100%). The results indicated that KASP applied to pooled samples may provide a semi-quantitative estimate of resistance. CONCLUSIONS: Our study points to the suitability of KASP for high-throughput genotyping of genotypes affecting pesticide resistance and semi-quantitative assessments of resistance allele frequencies in populations. © 2023 Society of Chemical Industry.

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.

Vacciniumusneoides (Ericaceae), a new species from Yunnan, China.

Vacciniumusneoides (Ericaceae), a new species from Fugong County of Yunnan Province, China is described and illustrated. This new species belongs to Vacciniumsect.Calcicolus and is most similar to V.brachyandrum, but differs in its branches hanging down, much smaller leaf blades, shorter inflorescences and pedicels, non-glandular tomentellate or densely pubescent inflorescence rachis and pedicels, densely white-pubescent hypanthium and pilose filaments.

The burden of cervical cancer in China.

Objective: Trends in the incidence, disability-adjusted life-years (DALYs), and mortality rate of cervical cancer remain unknown. Methods: The average annual percent changes (AAPCs) and relative risks (RR) in the incidence, DALYs, and mortality rate were determined using a joinpoint regression analysis; the net age, period, and cohort effects on above rates were evaluated. Results: A significant increase in age-standardized incidence (AAPC, 0.9%; 95CI: 0.8, 1.1) but significant decreases in age-standardized DALYs (AAPC, -0.4%; 95%CI: -0.60, -0.20) and the mortality rate (AAPC, -0.4%; 95CI: -0.6, -0.3) were observed. As for age-specific rates, the incidence was higher in younger age groups, and the DALYs and mortality rate were lower in older age groups. The effects of age included a slight but significant increase in the RR with advancing age from 35 to 94 years; the period effect included a significant increase in the incidence over the 2005-2019 periods; and the cohort effect included a substantial increase in the incidence from earlier to later birth cohorts. Conclusions: The incidence of cervical cancer increased from 1990 to 2019, particularly in younger age groups, and the DALYs and mortality rate decreased in the older age groups. Furthermore, the incidence increased with age, period, and cohort.

Natural borneol enhances the anti-cerebral ischaemia efficacy of formononetin in MCAO/R rats by promoting its delivery in the brain.

Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.

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.