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Abstract Purpose Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity. Methods This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters. Results Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p

Abstract Accurate prediction of drug-target interactions (DTIs) is crucial for advancing drug discovery and repurposing. Computational methods have significantly improved the efficiency of experimental predictions for drug-target interactions in Western medicine. However, accurately predicting the complex relationships between Chinese medicine ingredients and targets remains a formidable challenge due to the vast number and high heterogeneity of these ingredients. In this study, we introduce the CWI-DTI method, which achieves high-accuracy prediction of DTIs using a large dataset of interactive relationships of drug ingredients or candidate targets. Moreover, we present a novel dataset to evaluate the prediction accuracy of both Chinese and Western medicine. Through meticulous collection and preprocessing of data on ingredients and targets, we employ an innovative autoencoder framework to fuse multiple drug (target) topological similarity matrices. Additionally, we employ denoising blocks, sparse blocks, and stacked blocks to extract crucial features from the similarity matrix, reducing noise and enhancing accuracy across diverse datasets. Our results indicate that the CWI-DTI model shows improved performance compared to several existing state-of-the-art methods on the datasets tested in both Western and Chinese medicine databases. The findings of this study hold immense promise for advancing DTI prediction in Chinese and Western medicine, thus fostering more efficient drug discovery and repurposing endeavors. Our model is available at https://github.com/WANG-BIN-LAB/CWIDTI .

Abstract Efficient extraction of uranium from seawater is expected to provide virtually infinite fuel sources to power nuclear reactors and thus enable sustainable development of nuclear energy. The extraction efficiency for uranium greatly depends on the availability of active adsorption sites on the adsorbents. Maximization of the utilization rate of the binding sites in the adsorbent is vital for improving adsorption capacity. Herein, micro-redox reactors functioned by Cu(I)/Cu(II) conversion are constructed internally in an adsorbent bearing both amidoxime and carboxyl groups to induce active regeneration of the inactivated binding sites to enhance uranium capture. This adsorbent has high adsorption capacity (962.40 mg-U/g-Ads), superior anti-fouling ability as well as excellent uranium uptake (14.62 mg-U/g-Ads) in natural seawater after 56 days, placing it at the top of high-performance sorbent materials for uranium harvest from seawater.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

PurposeTo explore the role of deep learning (DL) and radiomics-based integrated approach based on contrast enhanced magnetic resonance imaging (CEMRI) for predicting early recurrence (ER) in hepatocellular carcinoma (HCC) patients after curative resection.MethodsTotal 165 HCC patients (ER, n = 96 vs. non-early recurrence (NER), n = 69) were retrospectively collected and divided into a training cohort (n = 132) and a validation cohort (n = 33). From pretreatment CEMR images, a total of 3111 radiomics features were extracted, and radiomics models were constructed using five machine learning classifiers (logistic regression, support vector machine, k-nearest neighbor, extreme gradient Boosting, and multilayer perceptron). DL models were established via three variations of ResNet architecture. The clinical-radiological (CR), radiomics combined with clinical-radiological (RCR), and deep learning combined with RCR (DLRCR) models were constructed. Model discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. The best-performing model was compared with the widely used staging systems and preoperative prognostic indexes.ResultsThe RCR model (area under the curve (AUC): 0.841 and 0.811) and the optimal radiomics model (AUC: 0.839 and 0.804) achieved better performance than the CR model (AUC: 0.662 and 0.752) in the training and validation cohorts, respectively. The optimal DL model (AUC: 0.870 and 0.826) outperformed the radiomics model in the both cohorts. The DL, radiomics, and CR predictors (aspartate aminotransferase (AST) and tumor diameter) were combined to construct the DLRCR model. The DLRCR model presented the best performance over any model, yielding an AUC, an accuracy, a sensitivity, a specificity of 0.917, 0.886, 0.889, and 0.882 in the training cohort and of 0.844, 0.818, 0.800, and 0.846 in the validation cohort, respectively. The DLRCR model achieved better clinical utility compared to the clinical staging systems and prognostic indexes.ConclusionBoth radiomics and DL models derived from CEMRI can predict HCC recurrence, and DL and radiomics-based integrated approach can provide a more effective tool for the precise prediction of ER for HCC patients undergoing resection.

Abstract Background GAox is a key enzyme involved in GA biosynthesis pathway and plays an important role in regulating various processes in plant life cycle. However, it has not been systematic, studies have been conducted in potato, which is the world's fourth largest food crop. Methods In this work, we systematically identified GAox gene family (StGAox) in potato by analyzing the potato genome sequence using a set of bioinformatics approaches, and analyze their physical, chemical properties, distribution on chromosomes, gene structure, conserved motifs, gene duplication events and expression patterns were analyzed. Results The results showed that a total of 33 GAox proteins were identified and unevenly distributed on 10 chromosomes. Based on their protein structure and phylogenetic characteristics, these 33 StGAoxes were divided into 5 distinct subclasses. Collinearity analysis revealed that there were 5 pairs of duplicated genes in the StGAox gene family, and all of which evolved under purifying selection. Analysis of RNA-seq data of double haploid (DM) potatoes under different tissues, abiotic stresses and hormone treatments showed that PG0002068, PG0024249 and PG0027963 were higher expressed in leaves, PG009427, PG0026762, PG0009021 and PG0021095 were higher expressed in tubers, PG2003479, PG0024249, PG0005698, and PG0009021were higher expressed in shoots than those of other tissues. In addition, the expression of PG0002068, PG2003479, PG0032156, PG0024249, and PG0021292 were up-regulated under mannitol and drought stress. Conclusions Comparative genome-wide analysis of StGAox genes and their expression analyses revealed that members of this family may be involved in tissue-specific developmental and abiotic stress responses. Graphical Abstract

Abstract Introduction Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). Methods and analysis A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 μm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student’s t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. Ethics and dissemination The study has been approved by the Institutional Review Board of Nanjing Lishui People’s Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. Trial registration Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

Abstract Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein–protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.

The dysfunction of pancreatic β-cells plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite numerous studies demonstrating the anti-inflammatory and antioxidant properties of puerarin, the protective effects of puerarin on β-cells remain poorly understood. Hence, this study aimed to explore the effects of puerarin on β-cell dysfunction in a hyperglycemic environment via the PINK/Parkin-mediated mitochondrial autophagy pathway. The alterations in cell viability of MIN6 cells exposed to glucose concentrations of 5 mM, 10 mM, 20 mM, and 30 mM for 24 h, 48 h, and 72 h, respectively, were assessed using the CCK-8 assay to optimize the modeling conditions. Subsequently, cellular insulin secretion was measured using enzyme-linked immunosorbent assay (ELISA), apoptosis rate by flow cytometry, mitochondrial membrane potential alteration by JC-1, cellular ROS production by the DCFH-DA fluorescent probe, and fusion of cellular autophagosomes and lysosomes through adenoviral infection analysis. Furthermore, gene and protein expression levels of the PINK/Parkin-mediated mitochondrial autophagy pathway and mitochondrial apoptosis pathway were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results indicated a significant decrease in MIN6 cell viability following 48 h of exposure to 30 mM glucose concentration. Puerarin intervention markedly attenuated ROS production, restored mitochondrial membrane potential, induced PINK/Parkin-mediated mitochondrial autophagy, suppressed activation of the mitochondrial apoptotic pathway, mitigated apoptosis, and enhanced insulin secretion in a high glucose (HG) environment. The findings of this investigation contribute to a deeper understanding of the precise mechanism underlying the protective effects of puerarin on β-cells and offer a theoretical foundation for advancing puerarin-based therapeutics aimed at ameliorating T2DM.

Thermal barrier coatings (TBCs) applications of yttria-stabilized (YSZ) are widely utilized on turbine blades of aviation engines due to its low thermal conductivity and high electrical conductivity. Predicting the infrared emissivity aids in monitoring blade operating temperatures, ensuring safe engine operation. This paper innovatively introduces a novel three-dimensional columnar EB-PVD coating model and utilizes the FDTD method to predict emissivity. The model exhibits strong consistency with experimental results for predicted emissivity in the short-wave infrared band (1.4–3 μm). The unique microstructure of the EB-PVD thermal barrier coatings significantly influence the infrared emissivity. The results indicate that vertically uniform arranged feathers exhibit higher emissivity levels compared to feathers with varying densities. Additionally, increasing the thickness of the ceramic top coating and reducing spherical closed porosity also enhance the emissivity levels. This research provides guidance for controlling emissivity at the microscale in the preparation of thermal barrier coatings.

Abstract BackgroundSexual transmission among men who have sex with men (MSM) has become the major HIV transmission route. However, limited research has been conducted to investigate the association between transactional sex (TS) and HIV incidence in China. ObjectiveThis study aims to investigate HIV incidence and distinguish sociodemographic and sexual behavioral risk factors associated with HIV incidence among MSM who engage in TS (MSM-TS) in China. MethodsWe conducted a prospective cohort study using a WeChat-based platform to evaluate HIV incidence among Chinese MSM, including MSM-TS in Ningbo, recruited from July 2019 until June 2022. At each visit, participants completed a questionnaire and scheduled an appointment for HIV counseling and testing on the WeChat-based platform before undergoing offline HIV tests. HIV incidence density was calculated as the number of HIV seroconversions divided by person-years (PYs) of follow-up, and univariate and multivariate Cox proportional hazards regression was conducted to identify factors associated with HIV incidence. ResultsA total of 932 participants contributed 630.9 PYs of follow-up, and 25 HIV seroconversions were observed during the study period, resulting in an estimated HIV incidence of 4.0 (95% CI 2.7-5.8) per 100 PYs. The HIV incidence among MSM-TS was 18.4 (95% CI 8.7-34.7) per 100 PYs, which was significantly higher than the incidence of 3.2 (95% CI 2.1-5.0) per 100 PYs among MSM who do not engage in TS. After adjusting for sociodemographic characteristics, factors associated with HIV acquisition were MSM-TS (adjusted hazard ratio [aHR] 3.93, 95% CI 1.29-11.93), having unprotected sex with men (aHR 10.35, 95% CI 2.25-47.69), and having multiple male sex partners (aHR 3.43, 95% CI 1.22-9.64) in the past 6 months. ConclusionsThis study found a high incidence of HIV among MSM-TS in Ningbo, China. The risk factors associated with HIV incidence include TS, having unprotected sex with men, and having multiple male sex partners. These findings emphasize the need for developing targeted interventions and providing comprehensive medical care, HIV testing, and preexposure prophylaxis for MSM, particularly those who engage in TS.

Abstract Background Plant U-box (PUB) E3 ubiquitin ligases have vital effects on various biological processes. Therefore, a comprehensive and systematic identification of the members of the U-box gene family in potato will help to understand the evolution and function of U-box E3 ubiquitin ligases in plants. Results This work identified altogether 74 PUBs in the potato (StPUBs) and examined their gene structures, chromosomal distributions, and conserved motifs. There were seventy-four StPUB genes on ten chromosomes with diverse densities. As revealed by phylogenetic analysis on PUBs within potato, Arabidopsis, tomato (Solanum lycopersicum), cabbage (Brassica oleracea), rice (Oryza sativa), and corn (Zea mays), were clustered into eight subclasses (C1-C8). According to synteny analysis, there were 40 orthologous StPUB genes to Arabidopsis, 58 to tomato, 28 to cabbage, 7 to rice, and 8 to corn. In addition, RNA-seq data downloaded from PGSC were utilized to reveal StPUBs’ abiotic stress responses and tissue-specific expression in the doubled-monoploid potato (DM). Inaddition, we performed RNA-seq on the ‘Atlantic’ (drought-sensitive cultivar, DS) and the ‘Qingshu NO.9’ (drought-tolerant cultivar, DT) in early flowering, full-blooming, along with flower-falling stages to detect genes that might be involved in response to drought stress. Finally, quantitative real-time PCR (qPCR) was carried out to analyze three candidate genes for their expression levels within 100 mM NaCl- and 10% PEG 6000 (w/v)-treated potato plantlets for a 24-h period. Furthermore, we analyzed the drought tolerance of StPUB25 transgenic plants and found that overexpression of StPUB25 significantly increased peroxidase (POD) activity, reduced ROS (reactive oxygen species) and MDA (malondialdehyde) accumulation compared with wild-type (WT) plants, and enhancing drought tolerance of the transgenic plants. Conclusion In this study, three candidate genes related to drought tolerance in potato were excavated, and the function of StPUB25 under drought stress was verified. These results should provide valuable information to understand the potato StPUB gene family and investigate the molecular mechanisms of StPUBs regulating potato drought tolerance.

A flexible and stable optical fiber sensor based on the Sagnac loop is proposed and experimentally demonstrated for the measurement of salinity and temperature, simultaneously. The sensing unit consists of a tapered polarization maintaining fiber (tPMF) and a fiber Bragg grating (FBG) connected in series in the Sagnac loop. The temperature response comes from the high birefringence of PMF inside Sagnac loop, and the salinity response is enabled by the high-order modes excited in the tapered area of PMF. Besides, the FBG is for temperature compensation. We have succeeded in implementing dual-parameter measurements with the sensitivities of 0.356 nm/‰ for salinity and 0.616 nm/°C for temperature, respectively. The designed sensor has the potential for long-term monitoring of real ocean states.

This paper presents an innovative and comprehensive methodology for loaded tooth contact analysis (LTCA) of spiral bevel gears, integrating ease-off surface computation with high-precision virtual generating tooth surfaces. The methodology integrates an error-sensitivity analysis model with a semi-analytical LTCA model for spiral bevel gears based on ease-off surfaces, developed using a Universal Generation Model. By leveraging sophisticated corrections in the machining process, the desired ease-off surfaces are obtained, ensuring the accuracy of the generated tooth surfaces. This simulation ensures minimal errors between theoretical and virtual generating tooth surfaces, providing a reliable basis for LTCA. The LTCA model is formulated using CNC-generated tooth surfaces, focusing on misalignments such as pinion offset, adjustment errors, and angular position errors along the pinion and gear axis. The feasibility and effectiveness of the proposed method are verified through comparisons with LTCA software analysis results, demonstrating its high accuracy in predicting the impact of misalignments on contact patterns and load distribution. This integrated approach offers significant advancements in the design and analysis of spiral bevel gears, providing a robust tool for predicting and analyzing gear performance under various misalignment conditions. The combined methodology enhances the reliability and accuracy of LTCA, ensuring optimal performance and durability of spiral bevel gears in practical applications.

Pyrabactin resistance 1-like (PYL) proteins are abscisic acid (ABA) receptors that play a crucial role in the plant’s response to adverse environmental conditions. However, as of yet, there is limited research on the role of PYL proteins in potato. In this study, a potato PYL gene, StPYL8-like, was identified through transcriptome analysis under drought stress. Molecular characterization revealed that the StPYL8-like protein possesses a highly conserved PYL family domain. Evolutionary analysis demonstrated that StPYL8-like protein clusters with various PYL proteins are involved in stress responses across different species. Functional assays showed that StPYL8-like robustly responds to different abiotic stresses, including drought and ABA treatment. Furthermore, the transient and stable expressions of StPYL8-like in tobacco enhanced their drought resistance, leading to increased plant height, leaf number, and fresh weight, as well as an improved root system. Transgenic tobacco carrying the StPYL8-like gene exhibited lower malondialdehyde (MDA) levels and higher proline accumulation and antioxidant enzyme activity compared to wild-type plants under drought conditions. Moreover, StPYL8-like upregulated the expression of stress-responsive genes (NtRD29A, NtLEA5, NtP5CS, NtPOD, NtSOD, and NtCAT) in transgenic plants subjected to drought stress. Collectively, these findings highlight the positive regulatory role of the StPYL8-like gene in enhancing potato plants’ response to drought stress.

Mapping benthic reefs at high resolution and accuracy is vital for the management and conservation of coral habitats. Optical remote sensing data has emerged as a valuable tool for large-scale reef mapping in the past decades, with numerous data sets and methods being utilised and developed. In this study, we present a comprehensive comparison of optical remote sensing based bathymetry and benthic mapping methods. We use different optical data including WorldView-2 stereo and Sentinel-2 imagery to map the water depths of coral reef areas in the Xisha region of the South China Sea. Bathymetry data derived from photogrammetric and linear regression methods are compared to the reprocessed Ice, Cloud and land Elevation Satellite-2 (ICESat-2) data. We find that the linear regression method (root-mean-square-error, RMSE = 0.60 m) outperforms photogrammetry (RMSE = 1.02 m), and the higher resolution WorldView-2 data yields less systematic biases than Sentinel-2 data. Considering that water depths reflect changes in temperature and light, which are critical factors influencing coral reef distribution, we propose to use satellite-derived bathymetry as a feature for coral reef classification. We demonstrate that combining topography and spectral information can improve the overall mapping accuracy, particularly for compositions characterised by sharp boundaries.

The synthesis or derivation of a series of structural analogues based on natural products is a common strategy for discovering antitumor drugs. As a unique natural diterpene derived from Trigonostemon howii, 3,4-seco-sonderianol (1) exhibited moderate cytotoxic effects. To improve the activity, a new diterpene derivative (1b) with a mitochondrial targeting function was synthesized by coupling triphenylphosphine to compound 1. Compared to the parent molecule, the antitumor activity of 1b increased greatly. A series of mechanistic experiments revealed that compound 1b induced cancer cell apoptosis and inhibited cancer cell migration by targeting the mitochondria and regulating the STAT3 and FAK signaling pathways. Meanwhile, 1b was found to inhibit angiogenesis in a transgenic zebrafish model. It is worth noting that 1b also demonstrated excellent antitumor effects in zebrafish tumor xenotransplantation models. All the evidence supports that compound 1b targeting mitochondria has the potential to be a candidate for an antitumor drug.

Abstract Background Continuous cropping can reduce soil quality and affect rhizosphere metabolism, ultimately reducing crop yield. Crop rotation can mitigate the damage caused by continuous cropping, but different crop rotation patterns respond differently to soil quality and rhizosphere metabolism. We investigated the effects of different cropping patterns on soil physicochemical properties, enzyme activities, microbial quantity, and rhizosphere metabolism of continuous potato cropping based on a long-term field study from 2018 to 2022. The experiment was set up with the following three treatments: potato (Solanum tuberosum L.)-potato-potato-potato-potato (CK), potato-potato-potato-pea (Pisum arvense L.)-potato (T1), and potato-potato-potato-faba bean (Vicia faba L.)-potato (T2). Results The results showed that pea-potato rotation (T1) and faba bean-potato rotation (T2) significantly improved soil physicochemical properties and microbial quantity, enhanced enzyme activity, and increased yield by 21.19% and 28.38%, respectively, compared with the continuous potato crop. Non-targeted metabolomics analysis showed that the differential metabolites of pea-potato and faba bean-potato rotation were mainly nucleotides, organic acids and derivatives, and flavonoids compared to continuous potato cropping. These differential metabolites are mainly enriched in the ABC transporter, purine metabolism, pyrimidine metabolism, and phenylalanine metabolism pathways. Combined analyses showed that legume-potato rotations improved soil physicochemical properties, enzyme activities, and microbial quantity of continuous potato cropping, ultimately increasing tuber yields. In addition, correlation analyses showed that differential metabolites significantly enriched in purine and phenylalanine metabolism (l-Tyrosine, Trans-Cinnamic acid, Guanine, and Adenine) were also strongly associated with these measurements. Conclusions Therefore, we conclude that legume-potato rotations modulate the abundance and function of rhizosphere metabolites and significantly alter the low molecular metabolite profile of the soil under continuous potato conditions. Some of these important metabolites may play a part in the cycling of nutrients in the soil, making its physicochemical properties and microbial quantity better, raising the activity of soil enzymes, and ultimately increasing the yield of potato tubers. The above results indicate that legume-potato rotation has a positive effect on continuous potato soils. It lays a solid foundation for revealing the complex molecular network and metabolic pathways of microbial communities in soil after legume crop rotation. Graphical Abstract

Abstract Background Noninvasive and precise methods to estimate treatment response and identify hepatocellular carcinoma (HCC) patients who could benefit from transarterial chemoembolization (TACE) are urgently required. The present study aimed to investigate the ability of intratumoral and peritumoral radiomics based on contrast-enhanced magnetic resonance imaging (CE-MRI) to preoperatively predict tumor response to TACE in HCC patients. Methods A total of 138 patients with HCC who received TACE were retrospectively included and randomly divided into training and validation cohorts at a ratio of 7:3. Total 1206 radiomics features were extracted from arterial, venous, and delayed phases images. The inter- and intraclass correlation coefficients, the spearman’s rank correlation test, and the gradient boosting decision tree algorithm were used for radiomics feature selection. Radiomics models on intratumoral region (TR) and peritumoral region (PTR) (3 mm, 5 mm, and 10 mm) were established using logistic regression. Three integrated radiomics models, including intratumoral and peritumoral region (T-PTR) (3 mm), T-PTR (5 mm), and T-PTR (10 mm) models, were constructed using TR and PTR radiomics scores. A clinical-radiological model and a combined model incorporating the optimal radiomics score and selected clinical-radiological predictors were constructed, and the combined model was presented as a nomogram. The discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. Results The T-PTR radiomics models performed better than the TR and PTR models, and the T-PTR (3 mm) radiomics model demonstrated preferable performance with the AUCs of 0.884 (95%CI, 0.821–0.936) and 0.911 (95%CI, 0.825–0.975) in both training and validation cohorts. The T-PTR (3 mm) radiomics score, alkaline phosphatase, tumor size, and satellite nodule were fused to construct a combined nomogram. The combined nomogram [AUC: 0.910 (95%CI, 0.854–0.958) and 0.918 (95%CI, 0.831–0.986)] outperformed the clinical-radiological model [AUC: 0.789 (95%CI, 0.709–0.863) and 0.782 (95%CI, 0.660–0.902)] in the both cohorts and achieved good calibration capability and clinical utility. Conclusions CE-MRI-based intratumoral and peritumoral radiomics approach can provide an effective tool for the precise and individualized estimation of treatment response for HCC patients treated with TACE.

Abstract Background As the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions. Methods Consecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013. Results A total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ 2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to

PYR/PYL/RCAR proteins are abscisic acid (ABA) receptors that play a crucial role in plant responses to abiotic stresses. However, there have been no research reports on potato PYL so far. In this study, a potato PYL gene named StPYL16 was identified based on transcriptome data under drought stress. Molecular characteristics analysis revealed that the StPYL16 protein possesses an extremely conserved PYL family domain. The tissue expression results indicated that the StPYL16 is predominantly expressed at high levels in the underground parts, particularly in tubers. Abiotic stress response showed that StPYL16 has a significant response to drought treatment. Further research on the promoter showed that drought stress could enhance the activation activity of the StPYL16 promoter on the reporter gene. Then, transient and stable expression of StPYL16 in tobacco enhanced the drought resistance of transgenic plants, resulting in improved plant height, stem thickness, and root development. In addition, compared with wild-type plants, StPYL16 transgenic tobacco exhibited lower malondialdehyde (MDA) content, higher proline accumulation, and stronger superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities. Meanwhile, StPYL16 also up-regulated the expression levels of stress-related genes (NtSOD, NtCAT, NtPOD, NtRD29A, NtLEA5, and NtP5CS) in transgenic plants under drought treatment. These findings indicated that the StPYL16 gene plays a positive regulatory role in potato responses to drought stress.

A novel demodulation scheme for a point-type fiber sensor is designed for salinity concentration monitoring based on a Sagnac interferometer (SI) composed of a tapered polarization-maintaining fiber (TPMF) and optical time stretching technology. The SI, constructed using a PMF with a taper region of 5.92 μm and an overall length of 30 cm, demonstrated a notable enhancement in the evanescent field, which intensifies the interaction between the light field and external salinity. This enhancement allows for a direct assessment of salinity concentration changes by analyzing the variations in the SI reflection spectra and the experimental results indicate that the sensitivity of the sensor is 0.151 nm/‰. In contrast to traditional fiber optic sensors that depend on spectral demodulation with slower response rates, this work introduces a new approach where the spectral shift is translated to the time domain, utilizing a dispersion compensation fiber (DCF) with the demodulation rate reaching up to 50 MHz. The experimental outcomes reveal that the sensor exhibits a sensitivity of −0.15 ns/‰ in the time domain. The designed sensor is anticipated to play a pivotal role in remote, real-time monitoring of ocean salinity.

Investigating the optimal laser processing parameters for industrial purposes can be time-consuming. Moreover, an exact analytic model for this purpose has not yet been developed due to the complex mechanisms of laser processing. The main goal of this study was the development of a backpropagation neural network (BPNN) with a grey wolf optimization (GWO) algorithm for the quick and accurate prediction of multi-input laser etching parameters (energy, scanning velocity, and number of exposures) and multioutput surface characteristics (depth and width), as well as to assist engineers by reducing the time and energy require for the optimization process. The Keras application programming interface (API) Python library was used to develop a GWO-BPNN model for predictions of laser etching parameters. The experimental data were obtained by adopting a 30 W laser source. The GWO-BPNN model was trained and validated on experimental data including the laser processing parameters and the etching characterization results. The R2 score, mean absolute error (MAE), and mean squared error (MSE) were examined to evaluate the prediction precision of the model. The results showed that the GWO-BPNN model exhibited excellent accuracy in predicting all properties, with an R2 value higher than 0.90.

The initial triggering mechanism of nitromethane is investigated by first-principles molecular dynamics simulations and temperature-dependent Raman spectroscopy experiment. The Raman spectra at different temperature are obtained by Car-Parrinello molecular dynamics simulation to explore the activated vibration modes caused by low-temperature heat. The temperature-dependent Raman spectra experiment is constructed to compare with the theoretical data. Each possible initial reaction path caused by the activated vibration mode is analyzed to reveal the triggering mechanism of the initial chemical bond breaking for nitromethane. The results show that the intermolecular double-proton transfer is the first reaction step which is triggered by the intermolecular hydrogen bond reinforced with the active C–H stretching vibration (near 3000 cm−1), which is not reported before. The scanning energy barrier related to the increase of C–H bond lengths is about 60 kcal/mol, which is consistent with the calculated activation barrier (59.8 kcal/mol) of intermolecular proton transfer reaction. This proves the reliability of our conclusions. The results provide a new interpretation for the long-debated initial decomposition mechanism of nitromethane.

Abstract Background Potato (Solanum tuberosum L.) continuous cropping causes the decrease of tuber yield, deterioration of quality and soil degradation in the semi-arid area. These negative effects can generally be mitigated by legume rotation and mulching. However, little is known about how can mulching and legume rotation alleviate the above damage through altering soil environment. Methods A field experiment was conducted to investigate changes in soil properties and microbial community in response to legume rotation and mulching under six planting patterns: potato continuous cropping without film mulching (PC), potato continuous cropping with film mulching (PCF), potato–broad bean rotation without film mulching (R1), potato–broad bean rotation with film mulching (R1F), potato–pea rotation without film mulching (R2) and potato–pea rotation with film mulching (R2F). Results Compared with the PC, the R1F and R2F had significantly enhanced the contents of alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), total carbon (TC) and total nitrogen (TN), but reduced soil pH and electrical conductivity (EC). The Shannon index of fungi in R1F and R2 was significantly higher than other treatments. The dominant bacterial and fungal phyla of each treatment was Proteobacteria and Ascomycota. R1, R1F, R2 and R2F enhanced the relative abundance of metabolic fungi and altered key differential microbial species. Soil EC, AN and AK were major factors influencing the soil bacterial and fungal communities. Conclusion Overall, the study demonstrated that potato-broad bean/pea rotation with mulching can be adopted as the preferred cropping systems to alleviate potato continuous cropping obstacles through enhancing soil fertility and regulating soil microbial communities in the semi-arid of Loess Plateau, China. Graphical Abstract

Highlights 1. Glutathione affected the synthesis of phenylpropanoid in the potato. 2. Glutathione affected the levels of plant hormone and the expression of related genes in potato. 3. Glutathione enhanced the tolerance of potato to cadmium stress. 4. Some genes play an important role in potato response to cadmium stress.

Addressing the current issue of limited control methods for badminton serving devices, this paper proposes a vision-based multimodal control system and method for badminton serving. The system integrates computer vision recognition technology with traditional control methods for badminton serving devices. By installing vision capture devices on the serving device, the system identifies various human body postures. Based on the content of posture information, corresponding control signals are sent to adjust parameters such as launch angle and speed, enabling multiple modes of serving. Firstly, the hardware design for the badminton serving device is presented, including the design of the actuator module through 3D modeling. Simultaneously, an embedded development board circuit is designed to meet the requirements of multimodal control. Secondly, in the aspect of visual perception for human body recognition, an improved BlazePose candidate region posture recognition algorithm is proposed based on existing posture recognition algorithms. Furthermore, mappings between posture information and hand information are established to facilitate parameter conversion for the serving device under different postures. Finally, extensive experiments validate the feasibility and stability of the developed system and method.

As global arid conditions worsen and groundwater resources diminish, drought stress has emerged as a critical impediment to plant growth and development globally, notably causing declines in crop yields and even the extinction of certain cultivated species. Numerous studies on drought resistance have demonstrated that DNA methylation dynamically interacts with plant responses to drought stress by modulating gene expression and developmental processes. However, the precise mechanisms underlying these interactions remain elusive. This article consolidates the latest research on the role of DNA methylation in plant responses to drought stress across various species, focusing on methods of methylation detection, mechanisms of methylation pattern alteration (including DNA de novo methylation, DNA maintenance methylation, and DNA demethylation), and overall responses to drought conditions. While many studies have observed significant shifts in genome-wide or gene promoter methylation levels in drought-stressed plants, the identification of specific genes and pathways involved remains limited. This review aims to furnish a reference for detailed research into plant responses to drought stress through epigenetic approaches, striving to identify drought resistance genes regulated by DNA methylation, specific signaling pathways, and their molecular mechanisms of action.

Lithium-ion batteries are currently widely employed in a variety of applications. Precise estimation of the remaining useful life (RUL) of lithium-ion batteries holds significant function in intelligent battery management systems (BMS). Therefore, in order to increase the fidelity and stabilization of predicting the RUL of lithium-ion batteries, in this paper, an innovative strategy for RUL prediction is proposed by integrating a one-dimensional convolutional neural network (1D CNN) and a bilayer long short-term memory (BLSTM) neural network. Feature extraction is carried out through the input capacity data of the model using 1D CNN, and these deep features are used as the input of the BLSTM. The memory function of the BLSTM is applied to retain key information in the database and to better understand the coupling relationship among consecutive time series data along the time axis, thereby effectively predicting the RUL trends of lithium-ion batteries. Two different types of lithium-ion battery datasets from NASA and CALCE were used to verify the effectiveness of the proposed method. The results show that the proposed method achieves higher prediction accuracy, demonstrates stronger generalization capabilities, and effectively reduces prediction errors compared to other methods.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

The lipoxygenases (LOXs) are non-heme iron-containing dioxygenases that play an important role in plant growth and defense responses. There is scarce knowledge regarding the LOX gene family members and their involvement in biotic and abiotic stresses in potato. In this study, a total of 17 gene family members (StLOXs) in potato were identified and clustered into three subfamilies: 9-LOX type I, 13-LOX type I, and 13-LOX type II, with eleven, one, and five members in each subfamily based on phylogenetic analysis. By exploiting the RNA-seq data in the Potato Genome Sequencing Consortium (PGSC) database, the tissue-specific expressed and stress-responsive StLOX genes in double-monoploid (DM) potato were obtained. Furthermore, six candidate StLOX genes that might participate in drought and salt response were determined via qPCR analysis in tetraploid potato cultivars under NaCl and PEG treatment. Finally, the involvement in salt stress response of two StLOX genes, which were significantly up-regulated in both DM and tetraploid potato under NaCl and PEG treatment, was confirmed via heterologous expression in yeast under salt treatment. Our comprehensive analysis of the StLOX family provides a theoretical basis for the potential biological functions of StLOXs in the adaptation mechanisms of potato to stress conditions.

Abstract Ferroptosis, an iron‐dependent form of regulated cell death driven by excessive accumulation of lipid peroxides, has become a promising strategy in cancer treatment. Cancer cells exploit antioxidant proteins, including Ferroptosis Suppressor Protein 1 (FSP1), to prevent ferroptosis. In this study, it is found that the E3 ubiquitin ligase TRIM21 bound to FSP1 and mediated its ubiquitination on K322 and K366 residues via K63 linkage, which is essential for its membrane translocation and ferroptosis suppression ability. It is further verified the protective role of the TRIM21‐FSP1 axis in RSL3‐induced ferroptosis in cancer cells and a subcutaneous tumor model. Moreover, TRIM21 is highly expressed in multiple gastrointestinal (GI) tumors, and its expression is further stimulated upon ferroptosis induction in cancer cells and the KPC mouse model. In summary, This study identifies TRIM21 as a negative regulator of ferroptosis through K63 ubiquitination of FSP1, which can serve as a therapeutic target to enhance the chemosensitivity of tumors based on ferroptosis induction.

Interactions between the monsoon and decadal oscillations in the Pacific and Atlantic have influenced the multidecadal variability of precipitation in eastern China over the past 1150 years, according to stable oxygen isotope records from three stalagmites.

Abstract Background Pancreatic ductal adenocarcinoma is prone to metastasis, resulting in short survival and low quality of life. LncRNAs are pivotal orchestrators that participate in various tumor progress. The underlying role and mechanism of lncRNA FAM83H-AS1 is still unknown in PDAC progression. Methods To address this issue, firstly, we profiled and analyzed the aberrant lncRNA expression in TCGA database and identified FAM83H-AS1 as the most effective one in promoting the migration of pancreatic cancer cells. Then, the expression levels of FAM83H-AS1 in patient’s serum, tumor tissues and PDAC cells were detected using RT-qPCR, and FAM83H-AS1 distribution in PDAC cells was determined by performing FISH and RT-qPCR. Next, a series of in vivo and in vitro functional assays were conducted to elucidate the role of FAM83H-AS1 in cell growth and metastasis in PDAC. The regulatory relationship between FAM83H-AS1 and FAM83H (the homologous gene of FAM83H-AS1) was verified by performing protein and RNA degradation assays respectively. Co-IP assays were performed to explore the potential regulatory mechanism of FAM83H to β-catenin. Rescue assays were performed to validate the regulation of the FAM83H-AS1/FAM83H/β-catenin axis in PDAC progression. Results FAM83H-AS1 was highly expressed in the tumor tissues and serum of patients with PDAC, and was correlated with shorter survival. FAM83H-AS1 significantly promoted the proliferation, invasion and metastasis of PDAC cells, by protecting FAM83H mRNA from degradation. Importantly, FAM83H protein manifested the similar malignant functions as that of FAM83H-AS1 in PDAC cells, and could bind to β-catenin. Specifically, FAM83H could decrease the ubiquitylation of β-catenin, and accordingly activated the effector genes of Wnt/β-catenin signaling. Conclusions Collectively, FAM83H-AS1 could promote FAM83H expression by stabilizing its mRNA, allowing FAM83H to decrease the ubiquitylation of β-catenin, thus resulted in an amplified FAM83H-AS1/FAM83H/β-catenin signal axis to promote PDAC progression. FAM83H-AS1 might be a novel prognostic and therapeutic target for combating PDAC.

Natural products are one of the essential sources of innovative drugs. Trigothysoid N, a natural daphnane diterpenoid obtained from Trigonostemon thyrsoideus, possessed the strong ability to inhibit the proliferation of A549 cells. Besides interrupting the cell cycle, the mechanism examination revealed that trigothysoid N can inhibit tumor proliferation and migration by targeting mitochondria, regulating the STAT3/FAK signal pathway, and suppressing angiogenesis. In addition to the possible mechanism, in vivo antitumor experiments were performed to explore the potential of trigothysoid N for treating non-small cell lung cancer (NSCLC). Collectively, these findings supported the great potential of trigothysoid N as a hopeful therapeutic agent against NSCLC.

(1) Background: Potato is the most important tuber crop in the world that can contribute to food security. However, the crop has been shown to be sensitive to drought and its yields decline significantly during successive periods of stress. Drought triggers a number of responses in potato, ranging from physiological changes to fluctuations in growth rates and yields. In light of global climate change, it is important to understand the effects of thiamethoxam on potato growth and yield under drought conditions. (2) Methods: The objective was to evaluate the impact of thiamethoxam on improving drought resistance and yield of potato under drought conditions. The drought-tolerant and sensitive-genotypes Qingshu No. 9 and Atlantic were used for a two–year pot experiment. Potato seeds were coated with 70% thiamethoxam before sowing (treatment group (T)), with a control group without treatment (NT). Two experimental treatments were applied: normal irrigation (ND) and drought stress (D). (3) Results: The results showed that root length, plant yield, chlorophyll content and superoxide dismutase (SOD) activity significantly increased under both genotypes, while malondialdehyde (MDA) and proline (Pro) content were reduced under thiamethoxam under drought stress. The best indicators were obtained in the comprehensive evaluation for the T–D treatment, suggesting that the application of thiamethoxam under drought stress was more effective than normal irrigation. (4) Conclusions: Our results suggest that the application of thiamethoxam improves potato growth, thereby increasing drought tolerance and potato yield. However, thiamethoxam is a neonicotinoid pesticide, and the limitation of this study is that it did not explore the ecological effects of thiamethoxam, which need to be systematically studied in the future. Moreover, considering the potential risks of thiamethoxam to the environment, specific agronomic measures to effectively degrade thiamethoxam residue should be taken when it is applied in agricultural production.

The C3HC4 RING finger gene (RING-HC) family is a zinc finger protein crucial to plant growth. However, there have been no studies on the RING-HC gene family in potato. In this study, 77 putative StRING-HCs were identified in the potato genome and grouped into three clusters based on phylogenetic relationships, the chromosome distribution, gene structure, conserved motif, gene duplication events, and synteny relationships, and cis-acting elements were systematically analyzed. By analyzing RNA-seq data of potato cultivars, the candidate StRING-HC genes that might participate in tissue development, abiotic stress, especially drought stress, and anthocyanin biosynthesis were further determined. Finally, a StRING-HC gene (Soltu.DM.09G017280 annotated as StRNF4-like), which was highly expressed in pigmented potato tubers was focused on. StRNF4-like localized in the nucleus, and Y2H assays showed that it could interact with the anthocyanin-regulating transcription factors (TFs) StbHLH1 of potato tubers, which is localized in the nucleus and membrane. Transient assays showed that StRNF4-like repressed anthocyanin accumulation in the leaves of Nicotiana tabacum and Nicotiana benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter activated by StAN1 and StbHLH1. The results suggest that StRNF4-like might repress anthocyanin accumulation in potato tubers by interacting with StbHLH1. Our comprehensive analysis of the potato StRING-HCs family contributes valuable knowledge to the understanding of their functions in potato development, abiotic stress, hormone signaling, and anthocyanin biosynthesis.

Railway catenary galloping, induced by aerodynamic instability, poses a significant threat by disrupting the electric current connection through sliding contact with the contact wire. This disruption leads to prolonged rail service interruptions and damage to the catenary’s suspension components. This paper delves into the exploration of optimizing the catenary system’s structure to alleviate galloping responses, addressing crucial parameters such as span length, stagger dropper distribution, and tension levels. Employing a finite element model, the study conducts simulations to analyze the dynamic response of catenary galloping, manipulating structural parameters within specified ranges. To ensure accurate and comprehensive exploration, the Sobol sequence is utilized to generate low-discrepancy, quasi-random, and super-uniform distribution sequences for the high-dimensional parameter inputs. Subsequent to the simulation phase, a genetic algorithm based on neural networks is employed to identify optimal parameter settings for suppressing catenary galloping, taking into account various constraints. The results gleaned from this investigation affirm that adjusting structural parameters can effectively diminish the galloping amplitude of the railway catenary. The most impactful strategy involves augmenting tension and reducing span length. Moreover, even when tension and span length are fixed, adjusting other parameters demonstrates efficacy in reducing galloping amplitudes. The adjustment of messenger-wire tension, dropper distribution, and stagger can achieve a 22.69% reduction in the maximum vertical galloping amplitude. Notably, maintaining a moderate stagger value and a short steady arm–dropper distance is recommended to achieve the minimum galloping amplitude. This research contributes valuable insights into the optimization of railway catenary systems, offering practical solutions to mitigate galloping-related challenges and enhance overall system reliability.

This paper presents an ultimate motion methodology of a face-milling spiral bevel gear pair to synthesize the mating tooth surfaces with a predesigned fourth-order motion curve. The methodology is to control some contact points along the contact path in the process of tooth contact analysis via application of an extended local synthesis which permits some transmission errors rather than zero at the concerned contact point. The modified offset motion correction is selected to demonstrate the proposed methodology. Applied torque corresponding to an elastic approach of 0.00635 mm at the mean contact point is calculated and the loaded tooth contact analysis is performed. Numerical results show that the extended local synthesis can effectively control the transmission errors on the predesigned fourth-order motion curve at arbitrarily predesigned contact points along the contact path of the spiral bevel gear pair. The tooth contact pattern for the actual tooth pair is scattered into three segments since the rotational motion of the driven gear at any instant angular position is dependent on the tooth pair with the least transmission error among the three adjacent tooth pairs. The actual tooth contact patterns of the spiral bevel gear pair become continuous when meshing tooth surfaces are elastically deformed.

Carcinoembryonic antigen (CEACAM5), as a broad-spectrum tumor biomarker, plays a crucial role in analyzing the therapeutic efficacy and progression of cancer. Herein, we propose a novel biosensor based on specklegrams of tapered multimode fiber (MMF) and two-dimensional convolutional neural networks (2D-CNNs) for the detection of CEACAM5. The microfiber is modified with CEA antibodies to specifically recognize antigens. The biosensor utilizes the interference effect of tapered MMF to generate highly sensitive specklegrams in response to different CEACAM5 concentrations. A zero mean normalized cross-correlation (ZNCC) function is explored to calculate the image matching degree of the specklegrams. Profiting from the extremely high detection limit of the speckle sensor, variations in the specklegrams of antibody concentrations from 1 to 1000 ng/mL are measured in the experiment. The surface sensitivity of the biosensor is 0.0012 (ng/mL)−1 within a range of 1 to 50 ng/mL. Moreover, a 2D-CNN was introduced to solve the problem of nonlinear detection surface sensitivity variation in a large dynamic range, and in the search for image features to improve evaluation accuracy, achieving more accurate CEACAM5 monitoring, with a maximum detection error of 0.358%. The proposed fiber specklegram biosensing scheme is easy to implement and has great potential in analyzing the postoperative condition of patients.

The elevated anthocyanin content of colored potatoes produces numerous health benefits in humans. However, there is a paucity of studies exploring the influence of environmental factors on anthocyanin components in colored potatoes. In our work, the Box–Behnken design was adopted to optimize anthocyanin extraction from colored potato tubers with ultrasound assistance. The response surface model was stable and reliable (R2 = 0.9775), and under optimal extraction conditions, namely an ultrasonic power of 299 W, an extraction time of 10 min, and a solid-liquid ratio of 1:30 (g/mL), the yield reached 4.33 mg/g. Furthermore, the anthocyanins of colored potato tubers grown at different altitudes were determined by high-performance liquid chromatography–mass spectrometry with optimized ultrasound-assisted extraction, the results showed that anthocyanin levels were the highest at high altitudes, whereas anthocyanins were almost undetectable at mid-altitude. Moreover, the types of anthocyanin compounds present in colored potatoes varied at different altitudes. The red clones exhibited substantial accumulation of pelargonidin across all three altitudes. In contrast, the main anthocyanins found in purple clones were malvidin, petunidin, and cyanidin. We identified the anthocyanin components with a strong correlation to the environment, thereby establishing a fundamental basis for the breeding of potato clones with high anthocyanin content.

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, rich polyphenols and polysaccharides from Pueraria Thomsonii Radix water extract (PTR) were quantitatively determined, and then the effects of PTR on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could alleviate pancreatic tissue damage, significantly decrease fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), urinary glucose (UGLU), and urinary albumin/creatinine ratio (UACR). Metabolomics showed that the Diabetes Control (DM) group produced 109 differential metabolites, of which 74 could be regulated by PTR. In addition, 16S rRNA sequencing was performed in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes(F/B) ratio and regulate three beneficial bacteria and one harmful bacterium. In conclusion, the results showed that PTR could ameliorate the T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric acid (GABA) may be involved in the regulation of the microbiota–gut–brain axis (MGB) and thus affects the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.

Abscisic acid (ABA) is an important stress hormone that affects plants’ tolerance to stress. Changes in the content of abscisic can have an impact on plant responses to abiotic stress. The abscisic acid aldehyde oxidase (AAO) plays a crucial role in the final step in the synthesis of abscisic acid; therefore, understanding the function of the AAO gene family is of great significance for insight into plants’ response to abiotic stresses. In this study, Solanum tuberosum AAO (StAAO) members were exhaustively explored using genome databases, and nine StAAOs were identified. Chromosomal location analysis indicated that StAAO genes mapped to 4 of the 14 potato chromosomes. Further analyses of gene structure and motif composition showed that members of the specific StAAO subfamily showed relatively conserved characteristics. Phylogenetic relationship analysis indicated that StAAOs proteins were divided into three major clades. Promoter analysis showed that most StAAO promoters contained cis-elements related to abiotic stress response and plant hormones. The results of tissue-specific expression analysis indicated that StAAO4 was predominantly expressed in the roots. Analysis of transcriptome data revealed that StAAO2/4/6 genes responded significantly to drought treatments. Moreover, further qRT-PCR analysis results indicated that StAAO2/4/6 not only significantly responded to drought stress but also to various phytohormone (ABA, SA, and MeJA) and abiotic stresses (salt and low temperature), albeit with different expression patterns. In summary, our study provides comprehensive insights into the sequence characteristics, structural properties, evolutionary relationships, and expression patterns of the StAAO gene family. These findings lay the foundation for a deeper understanding of the StAAO gene family and offer a potential genetic resource for breeding drought-resistant potato varieties.

As an important hormone response gene, Gretchen Hagen 3 (GH3) maintains hormonal homeostasis by conjugating excess auxin with amino acids during plant stress-related signaling pathways. GH3 genes have been characterized in many plant species, but they are rarely reported in potato. Here, 19 StGH3 genes were isolated and characterized. Phylogenetic analysis indicated that StGH3s were divided into two categories (group I and group III). Analyses of gene structure and motif composition showed that the members of a specific StGH3 subfamily are relatively conserved. Collinearity analysis of StGH3 genes in potato and other plants laid a foundation for further exploring the evolutionary characteristics of the StGH3 genes. Promoter analysis showed that most StGH3 promoters contained hormone and abiotic stress response elements. Multiple transcriptome studies indicated that some StGH3 genes were responsive to ABA, water deficits, and salt treatments. Moreover, qRT-PCR analysis indicated that StGH3 genes could be induced by phytohormones (ABA, SA, and MeJA) and abiotic stresses (water deficit, high salt, and low temperature), although with different patterns. Furthermore, transgenic tobacco with transient overexpression of the StGH3.3 gene showed positive regulation in response to water deficits by increasing proline accumulation and reducing the leaf water loss rate. These results suggested that StGH3 genes may be involved in the response to abiotic stress through hormonal signal pathways. Overall, this study provides useful insights into the evolution and function of StGH3s and lays a foundation for further study on the molecular mechanisms of StGH3s in the regulation of potato drought resistance.

Summary: Potatoes consist of flavonoids that provide health benefits for human consumers. To learn more about how potato tuber flavonoid accumulation and flesh pigmentation are controlled, we analyzed the transcriptomic and metabolomic profile of potato tubers from three colored potato clones at three developmental phases using an integrated approach. From the 72 flavonoids identified in pigmented flesh, differential abundance was noted for anthocyanins, flavonols, and flavones. Weighted gene co-expression network analysis further allowed modules and candidate genes that positively or negatively regulate flavonoid biosynthesis to be identified. Furthermore, an R2R3-MYB repressor StMYB3 and an R3-MYB repressor StMYBATV involved in the modulation of anthocyanin biosynthesis during tuber development were identified. Both StMYB3 and StMYBATV could interact with the cofactor StbHLH1 and repress anthocyanin biosynthesis. Our results indicate a feedback regulatory mechanism of a coordinated MYB activator-repressor network on fine-tuning of potato tuber pigmentation during tuber development.

The demand for high-performance underwater thrusters in marine engineering is increasing. The concealed, mobile, and efficient underwater ability of fish provides many directions for research. The black ghost knifefish uses only wavy ventral fins to swim and can hover and roll in the water. Based on the physiological and morphological characteristics of the black ghost knifefish, we explored the structure and movement mode of the ventral fin, so as to establish a two-degree of freedom (2-DOF) structural model and kinematic model. We reveal the motion mechanism of the undulating fin propulsion through the constructed model and computational fluid dynamics. It is found that when the fin surface fluctuates, a pair of vortices with opposite directions will be formed on the concave side of the fin surface. These vortices will produce a central jet on the fin surface, provide a reverse impulse for the ventral fin, and make the fin obtain power. In addition, we found that the propulsive force of the ribbon fin along the body direction is positively correlated with the swing amplitude and frequency of the fin movement, and the propulsive torque of the ribbon fin to realize the maneuvering movement increases first and then decreases with the increase of the torsion angle. The research on the structure and motion mechanism of the ribbon fin of the black ghost knifefish provides a basis for the development of a bionic prototype of multi-DOF motion and the control strategy of high-mobility motion.

Summary: Background: Epidermal growth factor receptor (EGFR) is an essential target for cancer treatment. However, EGFR inhibitor erlotinib showed limited clinical benefit in pancreatic cancer therapy. Here, we showed the underlying mechanism of tumor microenvironment suppressing the sensitivity of EGFR inhibitor through the pancreatic stellate cell (PSC). Methods: The expression of alpha-smooth muscle actin (α-SMA) and hypoxia marker in human pancreatic cancer tissues were detected by immunohistochemistry, and their correlation with overall survival was evaluated. Human immortalized PSC was constructed and used to investigate the potential effect on pancreatic cancer cell lines in hypoxia and normoxia. Luciferase reporter assay and Chromatin immunoprecipitation were performed to explore the potential mechanisms in vitro. The combined inhibition of EGFR and Met was evaluated in an orthotopic xenograft mouse model of pancreatic cancer. Findings: We found that high expression levels of α-SMA and hypoxia markers are associated with poor prognosis of pancreatic cancer patients. Mechanistically, we demonstrated that hypoxia induced the expression and secretion of HGF in PSC via transcription factor HIF-1α. PSC-derived HGF activates Met, the HGF receptor, suppressing the sensitivity of pancreatic cancer cells to EGFR inhibitor in a KRAS-independent manner by activating the PI3K-AKT pathway. Furthermore, we found that the combination of EGFR inhibitor and Met inhibitor significantly suppressed tumor growth in an orthotopic xenograft mouse model. Interpretation: Our study revealed a previously uncharacterized HIF1α-HGF-Met-PI3K-AKT signaling axis between PSC and cancer cells and indicated that EGFR inhibition plus Met inhibition might be a promising strategy for pancreatic cancer treatment. Funding: This study was supported by The National Natural Science Foundation of China.

Potato is one of the most important vegetable crops worldwide. Its growth, development and ultimately yield is hindered by drought stress condition. Breeding and selection of deep-rooted and drought-tolerant potato varieties has become a prime approach for improving the yield and quality of potato (Solanum tuberosum L.) in arid and semiarid areas. A comprehensive understanding of root development-related genes has enabled scientists to formulate strategies to incorporate them into breeding to improve complex agronomic traits and provide opportunities for the development of stress tolerant germplasm. Root response to drought stress is an intricate process regulated through complex transcriptional regulatory network. To understand the rooting depth and molecular mechanism, regulating root response to drought stress in potato, transcriptome dynamics of roots at different stages of drought stress were analyzed in deep (C119) and shallow-rooted (C16) cultivars. Stage-specific expression was observed for a significant proportion of genes in each cultivar and it was inferred that as compared to C16 (shallow-rooted), approximately half of the genes were differentially expressed in deep-rooted cultivar (C119). In C16 and C119, 11 and 14 coexpressed gene modules, respectively, were significantly associated with physiological traits under drought stress. In a comparative analysis, some modules were different between the two cultivars and were associated with differential response to specific drought stress stage. Transcriptional regulatory networks were constructed, and key components determining rooting depth were identified. Through the results, we found that rooting depth (shallow vs deep) was largely determined by plant-type, cell wall organization or biogenesis, hemicellulose metabolic process, and polysaccharide metabolic process. In addition, candidate genes responding to drought stress were identified in deep (C119) and shallow (C16) rooted potato varieties. The results of this study will be a valuable source for further investigations on the role of candidate gene(s) that affect rooting depth and drought tolerance mechanisms in potato.

Drought stress is a major threat to sustainable crop production worldwide. Despite the positive role of calcium (Ca2+) in improving plant drought tolerance in different crops, little attention has been paid to its role in mitigating drought stress in potatoes. In the present study, we studied the effect of foliar chelated sugar alcohol calcium treatments on two potato cultivars with different drought responses applied 15 and 30 days after limiting soil moisture. The results showed that the foliar application of calcium treatments alleviated the SPAD chlorophyll loss of the drought-sensitive cultivar ‘Atlantic’ (Atl) and reduced the inhibition of photosynthetic parameters, leaf anatomy deformation, and MDA and H2O2 content of both cultivars under drought stress. The Ca2+ treatments changed the expression of several Calcium-Dependent Protein Kinase (StCDPK) genes involved in calcium sensing and signaling and significantly increased antioxidant enzyme activities, average tuber weight per plant, and tuber quality of both cultivars. We conclude that calcium spray treatments improved the drought tolerance of both potato cultivars and were especially effective for the drought-sensitive cultivar. The present work suggests that the foliar application of calcium is a promising strategy to improve commercial potato yields and the economic efficiency of potato production under drought stress conditions.

The Vernier effect created using an incorporated Lyot–Sagnac loop is used to create an ultra-high sensitivity temperature sensor based on a ring laser cavity. Unlike standard double Sagnac loop systems, the proposed sensor is fused into a single Sagnac loop by adjusting the welding angle between two polarization-maintaining fibers (PMFs) to achieve effective temperature sensitivity amplification. The PMFs are separated into two arms of 0.8 m and 1 m in length, with a 45° angle difference between the fast axes. The sensor’s performance is examined both theoretically and experimentally. The experimental results reveal that the Vernier amplification effect can be achieved via PMF rotating shaft welding. The temperature sensitivity in the laser cavity can reach 2.391 nm/°C, which is increased by a factor of more than eight times compared with a single Sagnac loop structure (0.298 nm/°C) with a length of 0.8 m without the Vernier effect at temperatures ranging from 20 °C to 30 °C. Furthermore, unlike traditional optical fiber sensing that uses a broadband light source (BBS) for detection, which causes issues such as low signal-to-noise ratio and broad bandwidth, the Sagnac loop can be employed as a filter by inserting itself into the fiber ring laser (FRL) cavity. When the external parameters change, the laser is offset by the interference general modulation, allowing the external temperature to be monitored. The superior performance of signal-to-noise ratios of up to 50 dB and bandwidths of less than 0.2 nm is achieved. The proposed sensor has a simple structure and high sensitivity and is expected to play a role in biological cell activity monitoring.