StripeRust-Pocket: A Mobile-Based Deep Learning Application for Efficient Disease Severity Assessment of Wheat Stripe Rust.

Wheat stripe rust poses a marked threat to global wheat production. Accurate and effective disease severity assessments are crucial for disease resistance breeding and timely management of field diseases. In this study, we propose a practical solution using mobile-based deep learning and model-assisted labeling. StripeRust-Pocket, a user-friendly mobile application developed based on deep learning models, accurately quantifies disease severity in wheat stripe rust leaf images, even under complex backgrounds. Additionally, StripeRust-Pocket facilitates image acquisition, result storage, organization, and sharing. The underlying model employed by StripeRust-Pocket, called StripeRustNet, is a balanced lightweight 2-stage model. The first stage utilizes MobileNetV2-DeepLabV3+ for leaf segmentation, followed by ResNet50-DeepLabV3+ in the second stage for lesion segmentation. Disease severity is estimated by calculating the ratio of the lesion pixel area to the leaf pixel area. StripeRustNet achieves 98.65% mean intersection over union (MIoU) for leaf segmentation and 86.08% MIoU for lesion segmentation. Validation using an additional 100 field images demonstrated a mean correlation of over 0.964 with 3 expert visual scores. To address the challenges in manual labeling, we introduce a 2-stage labeling pipeline that combines model-assisted labeling, manual correction, and spatial complementarity. We apply this pipeline to our self-collected dataset, reducing the annotation time from 20 min to 3 min per image. Our method provides an efficient and practical solution for wheat stripe rust severity assessments, empowering wheat breeders and pathologists to implement timely disease management. It also demonstrates how to address the "last mile" challenge of applying computer vision technology to plant phenomics.

Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.

Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell-ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5-RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.

Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial.

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data.

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.

Characterization and prebiotic potential of polysaccharides from Rosa roxburghii Tratt pomace by ultrasound-assisted extraction.

In this study, polysaccharides (RRTPs) were extracted from Rosa roxburghii Tratt pomace by hot water or ultrasound (US)-assisted extraction. The structural properties and potential prebiotic functions of RRTPs were investigated. Structural characterization was conducted through HPAEC, HPGPC, GC-MS, FT-IR and SEM. Chemical composition analysis revealed that RRTPs extracted by hot water (RRTP-HW) or US with shorter (RRTP-US-S) or longer duration (RRTP-US-L) all consisted of galacturonic acid, galactose, glucose, arabinose, rhamnose and glucuronic acid in various molar ratio. US extraction caused notable reduction in molecular weight of RRTPs but no significant changes in primary structures. Fecal fermentation showed RRTPs could reshape microbial composition toward a healthier balance, leading to a higher production of beneficial metabolites including total short-chain fatty acids, curcumin, noopept, spermidine, 3-feruloylquinic acid and citrulline. More beneficial shifts in bacterial population were observed in RRTP-HW group, while RRTP-US-S had stronger ability to stimulate bacterial short-chain fatty acids production. Additionally, metabolic profiles with the intervention of RRTP-HW, RRTP-US-S or RRTP-US-L were significantly different from each other. The results suggested RRTPs had potential prebiotic effects which could be modified by power US via molecular weight degradation.

Efficient energy transport throughout conical implosions.

The double-cone ignition (DCI) scheme has been proposed as one of the alternative approaches to inertial confinement fusion, based on direct-drive and fast-ignition, in order to reduce the requirement for the driver energy. To evaluate the conical implosion energetics from the laser beams to the plasma flows, a series of experiments have been systematically conducted. The results indicate that 89%-96% of the laser energy was absorbed by the target, with moderate stimulated Raman scatterings. Here 2%-6% of the laser energy was coupled into the plasma jets ejected from the cone tips, which was mainly restricted by the mass reductions during the implosions inside the cones. The supersonic dense jets with a Mach number of 4 were obtained, which is favorable for forming a high-density, nondegenerated plasma core after the head-on collisions. These findings show encouraging results in terms of energy transport of the conical implosions in the DCI scheme.

Integrative methylome and transcriptome analysis reveals epigenetic regulation of Fusobacterium nucleatum in laryngeal cancer.

The aetiological mechanisms of Fusobacterium nucleatum in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by F. nucleatum in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of F. nucleatum in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that F. nucleatum promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the F. nucleatum-treated LSCC cell group; F. nucleatum abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of F. nucleatum in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.

Blockade of HMGB1 Reduces Inflammation and Pruritus in Atopic Dermatitis by Inhibiting Skin Fibroblasts Activation.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsed eczema and serious pruritus. High-mobility group box 1 protein (HMGB1) is a nuclear-binding protein and serves as an alarmin to promote inflammatory responses. METHODS: In this study, we established an AD mouse model by topical use of MC903 on ears and then used a specific HMGB1-binding peptide cIY8 and a HMGB1 inhibitor of glycyrrhizin to investigate HMGB1 on fibroblast activation in the pathogenesis of AD-like symptoms. RESULTS: Topical use of cIY8 and oral use of glycyrrhizin significantly improved the MC903-induced AD-like symptoms and pathological changes of the ears and scratching behavior in an AD mouse model; cIY8 treatment inhibited the higher mRNAs of IL-1α, IL-4, IL-5, IL-13, and IL-31 in the ears. In human fibroblasts, HMGB1 caused nuclear translocation of NF-kB, and the nuclear translocation could be inhibited by pre-treatment of HMGB1 with cIY8, suggesting that NF-κB signaling pathway participates in the HMGB1-induced inflammation of AD in fibroblasts and that cIY8 effectively impedes the function of HMGB1. Glycyrrhizin inhibited the Ca2+ signaling induced by ionomycin in mouse primary fibroblasts. The fibroblast-related proteins of α-SMA, Hsp47, and vimentin and the pruritus-related proteins of IL-33 and periostin were increased in the ears of the AD mouse model, the ratio of EdU incorporation became higher in mouse fibroblasts treated with MC903, and the higher proliferation and inflammatory responses of the fibroblasts could be reversed by glycyrrhizin treatment. CONCLUSIONS: Fibroblast activation by HMGB1 is one of the critical processes in the development of inflammation and pruritus in the AD mouse model. The specific HMGB1-binding peptide cIY8 and the HMGB1 inhibitor glycyrrhizin inactivate skin fibroblasts to alleviate the inflammation and pruritus in the AD mouse model. Peptide cIY8 may be topically used to treat AD patients in the future.

m6A­modified HOXC10 promotes HNSCC progression via co­activation of ADAM17/EGFR and Wnt/ß­catenin signaling.

The homeobox (HOX) gene family plays a fundamental role in carcinogenesis. However, the oncogenic mechanism of HOXC10 in head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, it was revealed that HOXC10 expression was significantly higher in HNSCC tissues than in adjacent tissues, and a high level of HOXC10 was closely associated with worse clinical outcomes. HOXC10 overexpression promoted HNSCC cell proliferation, migration, and invasion, both in vitro and in vivo. Mechanistically, chromatin immunoprecipitation sequencing revealed that HOXC10 drove the transcriptional activation of a disintegrin and metalloproteinase 17 (ADAM17), and the ADAM17/epidermal growth factor receptor (EGFR)/ERK1/2 signaling pathway facilitating the proliferation of HNSCC. Furthermore, mass spectrometric analysis indicated that HOXC10 interacted with ribosomal protein S15A (RPS15A) and enhanced RPS15A protein expression, activating the Wnt/ß­catenin pathway and contributing to invasion and metastasis of HNSCC. Additionally, the methylated RNA immune precipitation and RNA antisense purification assays showed that N6­methyladenosine (m6A) writer, methyltransferase­like 3, catalyzed m6A modification of the HOXC10 transcript, m6A reader insulin like growth factor 2 mRNA binding protein (IGF2BP)1 and IGF2BP3 involved in recognizing and stabilizing m6A­tagged HOXC10 mRNA. In summary, the present study identified HOXC10 as a promising candidate oncogene in HNSCC. The m6A modification­mediated HOXC10 promoted proliferation, migration, and invasion of HNSCC through co­activation of ADAM17/EGFR and Wnt/ß­catenin signaling, providing a novel diagnostic and prognostic biomarker and a potential therapeutic target for HNSCC.

The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.

Objective: Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. Methods: The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. Results: The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. Conclusion: Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.

Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma.

BACKGROUND: To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins. RESULTS: Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH-, which could be proven by H2O2 assay and N-acetylcysteine. CONCLUSIONS: Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

Tetraspanin CD63 reduces the progression and metastasis of head and neck squamous cell carcinoma via KRT1-mediated cell cycle arrest.

Despite the fact that metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma, fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. Tetraspanin CD63 has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC. In this study, we discovered that CD63 levels were abnormally altered in HNSCC tissue compared to adjacent tissue (n = 69 pairs), and that this was linked to prognosis. Through functional in vitro and in vivo experiments, the roles of CD63 in HNSCC were confirmed. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. Using mass spectrometry and co-immunoprecipitation assays, we discovered that KRT1 could be a direct interacting partner of CD63. Furthermore, both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue (n = 13 pairs), suggesting that CD63 and KRT1 play a role in reducing the metastasis of HNSCC. In summary, we reveal a previously unrecognized role of CD63 in regulating KRT1-mediated cell cycle arrest in HNSCC cells, and our findings contribute to defining an important mechanism of HNSCC progression and metastasis.

Experimental Demonstration of Laser Guiding and Wakefield Acceleration in a Curved Plasma Channel.

Curved plasma channels have been proposed to guide intense lasers for various applications, such as x-ray laser emission, compact synchrotron radiation, and multistage laser wakefield acceleration [e.g. J. Luo et al., Phys. Rev. Lett. 120, 154801 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.154801]. Here, a carefully designed experiment shows evidences of intense laser guidance and wakefield acceleration in a centimeter-scale curved plasma channel. Both experiments and simulations indicate that when the channel curvature radius is gradually increased and the laser incidence offset is optimized, the transverse oscillation of the laser beam can be mitigated, and the stably guided laser pulse excites wakefields and accelerates electrons along the curved plasma channel to a maximum energy of 0.7 GeV. Our results also show that such a channel exhibits good potential for seamless multistage laser wakefield acceleration.

Candidate loci for breeding compact plant-type soybean varieties.

Plant height and node number are important agronomic traits that influence yield in soybean (Glycine max L.). Here, to better understand the genetic basis of the traits, we used two recombinant inbred line (RIL) populations to detect quantitative trait loci (QTLs) associated with plant height and node number in different environments. This analysis detected 9 and 21 QTLs that control plant height and node number, respectively. Among them, we identified two genomic regions that overlap with Determinate stem 1 (Dt1) and Dt2, which are known to influence both plant height and node number. Furthermore, different combinations of Dt1 and Dt2 alleles were enriched in distinct latitudes. In addition, we determined that the QTLs qPH-13-SE and qPH-13-DW in the two RIL populations overlap with genomic intervals associated with plant height and the QTL qNN-04-DW overlaps with an interval associated with node number. Combining the dwarf allele of qPH-13-SE/qPH-13-DW and the multiple-node allele of qNN-04-DW produced plants with ideal plant architecture, i.e., shorter main stems with more nodes. This plant type may help increase yield at high planting density. This study thus provides candidate loci for breeding elite soybean cultivars for plant height and node number. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01352-2.

Corrigendum to 'Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/ß-catenin and MAPKs signaling pathways' [Genes & Diseases 9 (2022) 466-478].

[This corrects the article DOI: 10.1016/j.gendis.2020.07.014.].

Bayesian composite quantile regression for the single-index model.

By using a Gaussian process prior and a location-scale mixture representation of the asymmetric Laplace distribution, we develop a Bayesian analysis for the composite quantile single-index regression model. The posterior distributions for the unknown parameters are derived, and the Markov chain Monte Carlo sampling algorithms are also given. The proposed method is illustrated by three simulation examples and a real dataset.

A Curcumin-Modified Coordination Polymers with ROS Scavenging and Macrophage Phenotype Regulating Properties for Efficient Ulcerative Colitis Treatment.

Overexpression of classically activated macrophages (M1) subtypes and assessed reactive oxygen species (ROS) levels are often observed in patients with ulcerative colitis. At present, the treatment system of these two problems has yet to be established. Here, the chemotherapy drug curcumin (CCM) is decorated with Prussian blue analogs in a straightforward and cost-saving manner. Modified CCM can be released in inflammatory tissue (acidic environment), eventually causing M1 macrophages to transform into M2 macrophages and inhibiting pro-inflammatory factors. Co(III) and Fe(II) have abundant valence variations, and the lower REDOX potential in CCM-CoFe PBA enables ROS clearance through multi-nanomase activity. In addition, CCM-CoFe PBA effectively alleviated the symptoms of UC mice induced by DSS and inhibited the progression of the disease. Therefore, the present material may be used as a new therapeutic agent for UC.

HIBLUP: an integration of statistical models on the BLUP framework for efficient genetic evaluation using big genomic data.

Human diseases and agricultural traits can be predicted by modeling a genetic random polygenic effect in linear mixed models. To estimate variance components and predict random effects of the model efficiently with limited computational resources has always been of primary concern, especially when it involves increasing the genotype data scale in the current genomic era. Here, we thoroughly reviewed the development history of statistical algorithms used in genetic evaluation and theoretically compared their computational complexity and applicability for different data scenarios. Most importantly, we presented a computationally efficient, functionally enriched, multi-platform and user-friendly software package named 'HIBLUP' to address the challenges that are faced currently using big genomic data. Powered by advanced algorithms, elaborate design and efficient programming, HIBLUP computed fastest while using the lowest memory in analyses, and the greater the number of individuals that are genotyped, the greater the computational benefits from HIBLUP. We also demonstrated that HIBLUP is the only tool which can accomplish the analyses for a UK Biobank-scale dataset within 1 h using the proposed efficient 'HE + PCG' strategy. It is foreseeable that HIBLUP will facilitate genetic research for human, plants and animals. The HIBLUP software and user manual can be accessed freely at https://www.hiblup.com.

Both human diseases and agricultural traits can be predicted by incorporating phenotypic observations and a relationship matrix among individuals in a linear mixed model. Due to the great demand for processing massive data of genotyped individuals, the existing algorithms that require several repetitions of inverse computing on increasingly big dense matrices (e.g. the relationship matrix and the coefficient matrix of mixed model equations) have encountered a bottleneck. Here, we presented a software tool named 'HIBLUP' to address the challenges. Powered by our advanced algorithms (e.g. HE + PCG), elaborate design and efficient programming, HIBLUP can successfully avoid the inverse computing for any big matrix and compute fastest under the lowest memory, which makes it very promising for genetic evaluation using big genomic data.