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The 2022 MW6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap, providing an opportunity to study the regional seismogenic characteristics and seismic hazards. Here we use interferometric synthetic aperture radar (InSAR) and seismic data to study the mainshock rupture, early afterslip and the second largest aftershock of the 2022 Menyuan earthquake sequences. Our modeling results show that the mainshock ruptured the Lenglongling fault and the Tuolaishan fault with a maximum slip of ∼3 m. Rapid postseismic transient deformation occurred at the center of the Lenglongling fault. Our afterslip modeling reveals that the majority of afterslip occurred in the deeper part of the Lenglongling fault. A high-angle conjugated faulting event is found at the middle section of the Lenglongling fault. We use the stress inversion to investigate the possible triggering mechanism of the conjugated rupture event. The results indicate the maximum principal stress direction is in ∼222°, forming a ∼22° angle between the conjugated fault of second largest aftershock and the mainshock. The calculated normal stress changes indicate the region is within a pull-apart stress field, which favors such a conjugated rupturing event. Our study will help understand the rupture behavior of such kind of conjugated fault in other regions.

Cloud cover is a significant factor affecting the effectiveness of satellite-based Earth observations. Existing cloud detection algorithms primarily rely on imaging data from satellite sensors in the visible to near-infrared spectral range, making it challenging to achieve day-and-night cloud monitoring. Convolutional neural networks have shown outstanding performance in previous cloud detection algorithms due to their robust ability to extract local information. However, their inherent inductive bias limits their capacity to learn long-range semantic information. To address these challenges, we proposed SwinCloud, a U-shaped semantic segmentation network based on an enhanced Swin Transformer for cloud detection in the thermal infrared spectral range. Specifically, we augment the Swin Transformer's window attention module with a CNN-based parallel pathway to effectively model global-local information. We employ a feature fusion module before the final upsampling module in the decoder to better integrate low-level spatial information and high-level semantic information. On the Landsat-8 cloud detection dataset, our model outperforms state-of-the-art methods. When transferred to the SDGSAT-TIS cloud detection dataset, the mIOU of experiment results reaches 69.9%, demonstrating the strong transferability of SwinCloud across different sensors. We also applied SwinCloud to cloud detection in the visible bands of Landsat-8. The results demonstrated SwinCloud's generalization capability across different bands.

Abstract Background Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance. Methods After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated. Results (1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%). Conclusions The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.

Binomials have been relatively understudied compared to other types of multiword expressions (MWEs) in second language research, such as collocations and idioms. This study investigated English as a Foreign Language (EFL) learners’ processing of English binomials and how it is influenced by interlexical factors (L1-L2 congruency and L1-lexicalization) and intralexical factors (word and binomial frequency, binomial reversibility, and binomial predictability). Forty Chinese EFL learners participated in a phrase acceptability judgment task of 64 target binomials (16 congruent L1-lexicalized, 16 congruent L1-nonlexicalized, and 32 incongruent) and 64 non-binomial controls. Results revealed that learners experienced difficulty judging the formulaicity of binomials. They processed binomial stimuli significantly faster than non-binomial baselines, demonstrating a binomial phrase effect. They also processed L1-L2 congruent items faster and more accurately than incongruent items, showing a robust congruency effect. The congruent items which are lexicalized in the L1 showed further processing advantage than the non-lexicalized items, indicating a graded congruency effect. Moreover, binomial reversibility and binomial predictability (measured with cloze probability) also showed significant effects. These findings highlight the need to distinguish and investigate different types of congruency, explore appropriate measures for MWE predictability, and to examine binomials focusing on their unique features.

Alismatis Rhizoma (AR) is a crucial substance for discovering new triterpenoids to address hyperlipidemia and obesity. Currently, approximately 120 triterpenoids have been identified in AR, making the discovery of new triterpenoids increasingly challenging. Thus, based on the advantages of HPLC-HRMS, it was utilized to identify both reported and new triterpenoids, and then in-silico analysis was employed to predict the functions of these new triterpenoids. Twenty reported triterpenoids and four new triterpenoids (25-methoxy-16-oxo-11-anhydroalisol A, 25-methoxy-16-oxo-alisol A, 25-methoxy-16-oxo-alisol A 23-acetate, and 25-methoxy-16-oxo-alisol A 24-acetate) from AR were identified using HPLC-HRMS, and then KEGG analysis suggested four new triterpenoids might be activated the PPAR signaling pathway to relieve hyperlipemia. The results of PPI and molecular docking indicated PPARA might be the key targets for anti-hyperlipidemia of four new triterpenoids, of which 25-methoxy-16-oxo-11-anhydroalisol A has better binding activity with PPARA. Additionally, 25-methoxy-16-oxo-11-anhydroalisol A has more potential as a candidate drug because of its better absorption, distribution, metabolism, excretion, and lower toxicity. Hence, our findings proved there are new triterpenoids with anti-hyperlipidemia medicinal potential in AR, thereby guiding the direction of future works and reducing the consumption of time and financial resources.

Sentinel-1A/B data are crucial for retrieving numerical information about surface phenomena and processes. Coregistration of terrain observation by progressive scans (TOPS) data is a critical step in its application. TOPS data must be fundamentally co-registered with an accuracy of 0.001 pixels. However, various decorrelation factors due to natural vegetation and seasonal effects affect the coregistration accuracy of TOPS data. This paper proposed an enhanced spectral diversity coregistration method for dual-polarimetric (PolESD) Sentinel-1A/B TOPS data. The PolESD method suppresses speckle noise based on a unified non-local framework in dual-pol Synthetic Aperture Radar (SAR), and extracts the phase of the optimal polarization channel from the denoised polarimetric interferometric coherency matrix. Compared with the traditional ESD method developed for single-polarization data, the PolESD method can obtain more accurate coherence and phase and get more pixels for azimuth-offset estimation. In bare areas covered with low vegetation, the number of pixels selected by PolESD is more than the Boxcar method. It can also correct misregistration more effectively and eliminate phase jumps in the burst edge. Therefore, PolESD will help improve the application of TOPS data in low-coherence scenarios.

Abstract Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta‐analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta‐analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta‐analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa.

Pyriclobenzuron 11 PBU – pyriclobenzuron.(PBU) is a novel molluscicide developed to control Pomacea canaliculate, and little information on its environmental fate has been published. In this study, the photolysis of PBU in an aqueous environment was simulated using a xenon lamp. Results showed that the photolysis of PBU in water followed first-order kinetics, exhibiting a t0.5 of 95.1 h and 83.6 h in Milli-Q water and river water, respectively. Two main photolysis products 22 PPs – photolysis products.(PPs) were detected by HPLC-UV and identified by UPLC-Q/TOF MS, which were formed via the hydroxylation and photocatalytic hydro-dehalogenation of PBU, respectively. The initial relative abundance of photolysis product 1 33 PP-1 – photolysis product 1.(PP-1) in Milli-Q water was 1.55 times higher than that in river water. PP-1 was detected at 26.5 % and 76.8 % of the maximum relative abundance in the river water and Milli-Q water after 720 h, respectively. Photolysis product 2 44 PP-2 – photolysis product 2.(PP-2) was stable in water because of its weak hydrophilicity. The PP-2 detected after 720 h in Milli-Q water and river water was 93.7 % and 93.5 % of the maximum relative abundance, respectively. Finally, ECOSAR software was used to evaluate the acute aquatic toxicity of PBU and its PPs, revealing that the PPs had lower toxicity levels to non-target aquatic organisms.

Pymetrozine is used on potato (S. tuberosum) and Chrysanthemum morifolium (C. morifolium) to obtain greater yield and quality. However, pesticide use carries the potential for residues to remain and be detected on harvested crops. Therefore, the aim of this study was to estimate pesticide residues in S. tuberosum and C. morifolium products that are commercially available for human consumption and to assess the associated dietary risks. For this study, a total of 340 samples (200 S. tuberosum samples and 140 C. morifolium samples) were collected randomly from supermarkets and farmer’s markets. Residues of pymetrozine in S. tuberosum and C. morifolium were detected by using an established and validated QuECHERS-HPLC-MS / MS method, while a dietary risk assessment of pymetrozine in S. tuberosum and C. morifolium was performed using these data. The detection rates of pymetrozine in S. tuberosum and C. morifolium samples were 92.31% and 98.17%, respectively, with residues not more than 0.036 and 0.024 mg/kg, respectively. Based on these results, the dietary risk assessment indicated that the intake of pymetrozine residues in S. tuberosum and C. morifolium does not pose a health risk. This work improved our understanding of the potential exposure risk of pymetrozine in S. tuberosum and C. morifolium.

Timely response to earthquake characterization can facilitate earthquake emergency rescue and further scientific investigations. On June 1, 2022, MW 5.9 earthquake occurred in the southern area of the Longmenshan fault zone. This event also happened at the south end of the Dayi seismic gap and is the largest earthquake that has occurred in this seismic gap since the 1970 M 6.2 event. The slip-distribution model constrained by the seismic waveforms suggests a thrust-dominated faulting mechanism. The main slip occurs at a depth of ∼14 ​km, and the cumulative energy is released in the first 6 ​s. The variations of Coulomb stress caused by the mainshock show a positive change in the southwest area of the Dayi seismic gap, indicating possible activation of future earthquakes. In addition, we emphasize the importance of rapid estimation of deformation for near-field hazard delineation, especially when interferometric radar fails to image coseismic deformation in a high relief terrain.

In this study, the fate of two pesticides commonly used on cowpeas, thiamethoxam and pyraclostrobin, during the preparation of home-made pickled cowpeas was investigated using an improved QuEChERS method combined with UHPLC-MS/MS. Although pesticide residues were primarily distributed on cowpea samples, some were transferred to brine. The dissipation half-life of thiamethoxam on cowpea samples was significantly shorter than that of pyraclostrobin due to thiamethoxam’s higher water solubility. Thiamethoxam demonstrated a half-life of 5.12 ± 0.66 days, whereas pyraclostrobin exhibited a longer half-life of 71.46 ± 7.87 days. In addition, the degradation half-lives of these two pesticides in the whole system (cowpea and brine) were 45.01 ± 4.99 and 70.51 ± 5.91 days, respectively. This result indicates that the pickling did not effectively promote the degradation of thiamethoxam and pyraclostrobin. The metabolite clothianidin of thiamethoxam was not produced throughout the pickling process, but the metabolite BF 500-3 of pyraclostrobin was detected in cowpea samples. The detection rates for thiamethoxam, pyraclostrobin, and BF 500-3 in the 20 market samples were 10%, 70%, and 45%, respectively. However, the risk quotient analysis indicated that the risk of dietary intake of thiamethoxam and pyraclostrobin in pickled cowpeas by Chinese consumers was negligible.

Abstract Background Noninvasive prenatal diagnosis (NIPD) based on cell‐free DNA (cfDNA) has been introduced into the clinical application for some monogenic disorders but not for tuberous sclerosis (TSC) yet, which is an autosomal dominant disease caused by various variations in TSC1 or TSC2 gene. We aimed to explore the feasibility of NIPD on TSC. Methods We recruited singleton pregnancies at risk of TSC from 14 families with a proband child. Definitive NIPD for TSC was performed using targeted next‐generation sequencing of cfDNA in parallel with maternal white blood cell DNA (wbcDNA). The NIPD results were validated by amniocentesis or postnatal gene testing and follow‐up of the born children. Results Missense mutations, nonsense mutations, frameshift mutations, and splice‐site variants which were obtained through de‐novo, maternal, or paternal inheritance were included. The mean and minimum gestational weeks of NIPD were 17.18 ± 5.83 and 8 weeks, respectively. The NIPD results were 100% consistent with the amniocentesis or postnatal gene testing and follow‐up of the born children. Conclusion This study demonstrates that NIPD based on cfDNA is feasible for TSC, but required to be confirmed with more samples. Studies on TSC can contribute to the application and promotion of NIPD for monogenic disorders.

Comprehensive profiles of tumour and microenvironment are critical to understand heterogeneity in non-small cell lung cancer (NSCLC). Here, the authors profile 42 late-stage NSCLC patients with single-cell RNA-seq, revealing immune landscapes that are associated with cancer subtype or heterogeneity.

As device fabrication reach atomic scales, assembly of atomically defined components becomes crucial. Here, the authors demonstrate a low contamination transfer technique, using single-crystalline anthracene as medium, for placement of structure-specific carbon nanotubes with submicron accuracy.

Abstract Background The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML). Methods We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Results FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT 3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3 wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup. Conclusions Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.

The widespread use of pesticides poses significant risks to food and environmental safety. Imidacloprid is one of the most effective neuroactive neonicotinoid insecticides and is effective against a broad spectrum of piercing–sucking pests. A rapid, efficient, and high-throughput analysis method for the determination of imidacloprid was developed in four minor crops with six matrices (bamboo shoot, winter jujube, fresh and dry D. officinale, and fresh and dry Fritillaria) by solid-phase extraction and HPLC-MS/MS. The procedure showed satisfying recoveries (72~111%) and RSDs (1~13%). A total of 288 samples were tested in China (Aba and Luan). Imidacloprid residues were 100% detected in fresh and dry D. officinale and winter jujube, with concentrations ranging from 0.048 to 1.550 mg·kg−1. Imidacloprid residues were also abundant in fresh and dry Fritillaria (maximal concentration of 0.021 and 0.063 mg·kg−1, respectively), followed by bamboo shoot, which had the lowest detection rate of imidacloprid (6%). Using the risk quotient (RQ) method, the long-term (RQc) and short-term (RQa) dietary risks of imidacloprid in bamboo shoot, winter jujube, fresh and dry D. officinale, and fresh and dry Fritillaria were further monitored. Based on the imidacloprid residues in this paper, the RQc and RQa were 15.03% and 0.0008~1.7604%, respectively. The RQ values were far less than 100%, showing that Chinese consumers face little health risk as a result of imidacloprid intake.

Abstract Background With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues. Methods Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining. Results A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples. Conclusion We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

Metalaxyl is frequently used to protect a variety of crops from fungal diseases. This study aims to establish a method for the determination of metalaxyl in Chinese bayberry, fresh Dendrobium officinale (D. officinale), and dried D. officinale by gas chromatography-tandem mass spectrometry (GC-MS/MS) and further assess dietary risk. The samples were extracted with acetonitrile and purified by the dispersed solid phase extraction method. Chinese bayberry, fresh D. officinale, and dried D. officinale samples were collected from Hangzhou and Zhangzhou in 2021 to clarify metalaxyl residue levels. The metalaxyl was quantitated by the external standard method. In the range of 0.001–0.1 mg L−1, there was good linearity under the optimal conditions. The recoveries ranged from 83.90% to 110.47%, with relative standard deviations ranging from 0.86% to 5.81%. The detection rates in Chinese bayberry, fresh D. officinale, and dried D. officinale were 97.92%, 49.29%, and 50.71%, respectively. The dietary risk of metalaxyl residues in Chinese bayberry, fresh D. officinale, and dried D. officinale was acceptable for consumers.

The massive use of pesticides has brought great risks to food and environmental safety. It is necessary to develop reliable analytical methods and evaluate risks through monitoring studies. Here, a method was used for the simultaneous determination of flupyradifurone (FPF) and its two metabolites in fresh ginseng, dried ginseng, ginseng plants, and soil. The method exhibited good accuracy (recoveries of 72.8–97.5%) and precision (relative standard deviations of 1.1–8.5%). The field experiments demonstrated that FPF had half-lives of 4.5–7.9 d and 10.0–16.9 d in ginseng plants and soil, respectively. The concentrations of total terminal residues in soil, ginseng plants, dried ginseng, and ginseng were less than 0.516, 2.623, 2.363, and 0.641 mg/kg, respectively. Based on these results, the soil environmental risk assessment shows that the environmental risk of FPF to soil organisms is acceptable. The processing factors for FPF residues in ginseng were 3.82–4.59, indicating that the concentration of residues increased in ginseng after drying. A dietary risk assessment showed that the risk of FPF residues from long-term and short-term dietary exposures to global consumers were 0.1–0.4% and 12.07–13.16%, respectively, indicating that the application of FPF to ginseng at the recommended dose does not pose a significant risk to consumers.

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

In this study, an analytical method was developed for the rapid determination of 21 pesticides used in ginseng cultivation. All pesticides covered by this method have been registered by 2020 in China for use on ginseng. The extracts were cleaned up using zirconium-oxide-modified silica (Z-Sep) and primary secondary amine (PSA). The combination of Z-Sep and PSA provided good recovery for all analytes and the cleanest matrix background out of a number of PSA-based sorbent combinations, as indicated by high-performance liquid chromatography (HPLC) and gas chromatography (GC). Instrumental analysis was completed in 5 min using the ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The linearity (r > 0.99) for all analytes was satisfactory over the calibration range of 0.002–0.1 μg mL−1. Intraday recoveries (n = 5) at ginseng-spiked levels of 0.02, 0.05, 0.1, and 1 mg kg−1 ranged between 72% and 119%, with the corresponding relative standard deviations (RSDs), were less than 19%, while the interday recoveries (n = 15) ranged between 77% and 103%, and RSDs were less than 22%. Limits of quantitation (LOQs) ranged between 0.02 and 0.05 mg kg−1 for all 21 pesticides. This is a seminal study using Z-Sep for the efficient cleanup of ginseng samples, and it could present a practical method for future monitoring of pesticide residues in ginseng produced in China.

Pesticides are one of the abiotic stresses that have had an impact on the quality of agricultural products, especially in China. This study was the first to explore the soluble protein (SP) accumulation, peroxidase (POD) activity, and superoxide dismutase (SOD) activity variations in the stem and leaf of celery plants in the field after 2 h, 1, 3, 5, 8, 10, 14, 21, 28-day of spraying imidacloprid (IMI) and fenpyroximate (FEN) at various doses. The findings demonstrated that there was no notable difference in ultimate residues between 1 F and 10 F, and even with the 10 F treatment, the residues were not a concern. The SP accumulation alterations were mainly provoked by residues, which dramatically boosted in stem and eventually declined in leaf. The POD activity in celery was a dynamic process with a marked shift (enhanced and declined) when compared with non-pesticide treatment after 28 days. The field trial exhibited that the SOD was principally positioned in leaf whether pesticides were applied or not, which might be due to the distinctive structure of the celery leaf compared with the stem. No obvious linear relation between application dose and SOD activity was observed.

On 17 June 2019, an Ms6.0 earthquake occurred in Changning, Sichuan, China (Changning event), which was the largest earthquake on record within 50 km of the area. It attracted great attention as the area has the largest shale gas production in China as well as significant mineral salt production. Using the Interferometric Synthetic Aperture Radar (InSAR), we extract the coseismic deformation of the Changning event and two earlier Ms > 5.0 earthquakes which occurred in the same region (16 December 2018 Ms5.7 and 3 January 2019 Ms5.3) from the Sentinel-1 and ALOS2 data. We use nonlinear and linear methods to invert the fault models of the three earthquakes based on the deformation fields. The final model shows that the Changning event was caused by a fault with left-lateral strike and thrust slip. The strike is 124.3° with a dip angle of 43.4°. The seismic moment obtained by inversion is 5.28 × 1017 Nm, corresponding to Mw 5.78. Based on the fault models, we analyze the cause of the Changning earthquake considering the local tectonic setting, Coulomb stress change, mining, and fluid injection. We consider that the event may be related to salt mining. The two earlier Ms > 5.0 earthquakes may also play an important role in advancing the Changning earthquake.

In this study, an analytical method for the simultaneous determination of the novel insecticide flupyradifurone and its two metabolites in a variety of traditional Chinese herbal medicines was developed for the first time using high-performance liquid chromatography-tandem mass spectrometry. A simple and efficient method using dispersive solid-phase extraction was employed for the pretreatment of the samples. Several extractions and cleanup strategies were evaluated. The recoveries (n = 15) of flupyradifurone and its metabolites at three spiking levels were in the range 71.3%–101.7%, with corresponding intraday and interday relative standard deviations of 1.1%–14.8%. The limits of quantitation were 0.01 mg/kg for flupyradifurone and 0.1 mg/kg for its two metabolites. Overall, our developed method was sensitive and reliable for the fast screening of flupyradifurone and its two metabolites in traditional Chinese herbal medicine samples.

Abstract Although clinical antibiotic-resistant bacteria have attracted tremendous attention in the microbiology community, the resistant bacteria that persist in natural environments have been overlooked for a longtime. We previously proposed a new species Paramesorhizobium desertii, isolated from the soil of the Taklimakan Desert in China that is highly resistant to most β-lactam antibiotics. To identify potential β-lactamase(s) in this bacteria, we first confirmed the carbapenemase activity in the freeze–thawed supernatant of a P. desertii A-3-ET culture using the modified Hodge assay. We then identified a novel chromosome-encoded carbapenemase (PAD-1) in strain A-3-ET, using a shotgun proteomic analysis of the supernatant and genomic information. The bioinformatics analysis indicated that PAD-1 is a class A carbapenemase. Subsequent enzyme kinetic assays with purified PAD-1 confirmed its carbapenemase activity, which is similar to that of clinically significant class A carbapenemases, including BKC-1 and KPC-2. Because the location in which A-3-ET was isolated is not affected by human activity, PAD-1 is unlikely to be associated with the selection pressures exerted by modern antibiotics. This study confirmed the diversity of antibiotic-resistant determinants in the environmental resistome.

Aims/Introduction. The present study estimated the cost-effectiveness of bariatric surgery versus medication therapy for the management of recently diagnosed type 2 diabetes mellitus (T2DM) in obese patients from a Chinese health insurance payer perspective. Materials and Methods. A Markov model was established to compare the 40-year time costs and quality-adjusted life-years (QALYs) between bariatric surgery and medication therapy. The health-care costs in the bariatric surgery group, proportion of patients in each group with remission of diabetes, and state transition probabilities were calculated based on observed resource utilization from the hospital information system (HIS). The corresponding costs in the medication therapy group were derived from the medical insurance database. QALYs were estimated from previous literature. Costs and outcomes were discounted 5% annually. Results. In the base case analysis, bariatric surgery was more effective and less costly than medication therapy. Over a 40-year time horizon, the mean discounted costs were 86,366.55 RMB per surgical therapy patient and 113,235.94 CNY per medication therapy patient. The surgical and medication therapy patients lived 13.46 and 10.95 discounted QALYs, respectively. Bariatric surgery was associated with a mean health-care savings of 26,869.39 CNY and 2.51 additional QALYs per patient compared to medication therapy. Uncertainty around the parameter values was tested comprehensively in sensitivity analyses, and the results were robust. Conclusions. Bariatric surgery is a dominant intervention over a 40-year time horizon, which leads to significant cost savings to the health insurance payer and increases in health benefits for the management of recently diagnosed T2DM in obese patients in China.

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

Game theory—the scientific study of interactive, rational decision making—describes the interaction of two or more players from macroscopic organisms to microscopic cellular and subcellular levels. Life based on molecules is the highest and most complex expression of molecular interactions. However, using simple molecules to expand game theory for molecular decision-making remains challenging. Herein, we demonstrate a proof-of-concept molecular game-theoretical system (molecular prisoner’s dilemma) that relies on formation of the thymine⁻Hg2+⁻thymine hairpin structure specifically induced by Hg2+ and fluorescence quenching and molecular adsorption capacities of cobalt oxyhydroxide (CoOOH) nanosheets, resulting in fluorescence intensity and distribution change of polythymine oligonucleotide 33-repeat thymines (T33). The “bait„ molecule, T33, interacted with two molecular players, CoOOH and Hg2+, in different states (absence = silence and presence = betrayal), regarded as strategies. We created conflicts (sharing or self-interest) of fluorescence distribution of T33, quantifiable in a 2 × 2 payoff matrix. In addition, the molecular game-theoretical-system based on T33 and CoOOH was used for sensing Hg2+ over the range of 20 to 600 nM with the detection limit of 7.94 nM (3σ) and for determination of Hg2+ in pond water. Inspired by the proof-of-concept for molecular game theory, various molecular decision-making systems could be developed, which would help promote molecular information processing and generating novel molecular intelligent decision systems for environmental monitoring and molecular diagnosis and therapy.

BACKGROUND: Yersinia pestis synthesizes the attached biofilms in the flea proventriculus, which is important for the transmission of this pathogen by fleas. The hmsHFRS operons is responsible for the synthesis of exopolysaccharide (the major component of biofilm matrix), which is activated by the signaling molecule 3', 5'-cyclic diguanylic acid (c-di-GMP) synthesized by the only two diguanylate cyclases HmsT, and YPO0449 (located in a putative operonYPO0450-0448). METHODOLOGY/PRINCIPAL FINDINGS: The phenotypic assays indicated that the transcriptional regulator Fur inhibited the Y. pestis biofilm production in vitro and on nematode. Two distinct Fur box-like sequences were predicted within the promoter-proximal region of hmsT, suggesting that hmsT might be a direct Fur target. The subsequent primer extension, LacZ fusion, electrophoretic mobility shift, and DNase I footprinting assays disclosed that Fur specifically bound to the hmsT promoter-proximal region for repressing the hmsT transcription. In contrast, Fur had no regulatory effect on hmsHFRS and YPO0450-0448 at the transcriptional level. The detection of intracellular c-di-GMP levels revealed that Fur inhibited the c-di-GMP production. CONCLUSIONS/SIGNIFICANCE: Y. pestis Fur inhibits the c-di-GMP production through directly repressing the transcription of hmsT, and thus it acts as a repressor of biofilm formation. Since the relevant genetic contents for fur, hmsT, hmsHFRS, and YPO0450-0448 are extremely conserved between Y. pestis and typical Y. pseudotuberculosis, the above regulatory mechanisms can be applied to Y. pseudotuberculosis.