Assessing the biodiversity of rhizosphere and endophytic fungi in Knoxia valerianoides under continuous cropping conditions.

BACKGROUND: Rhizosphere and endophytic fungi play important roles in plant health and crop productivity. However, their community dynamics during the continuous cropping of Knoxia valerianoides have rarely been reported. K. valerianoides is a perennial herb of the family Rubiaceae and has been used in herbal medicines for ages. Here, we used high-throughput sequencing technology Illumina MiSeq to study the structural and functional dynamics of the rhizosphere and endophytic fungi of K. valerianoides. RESULTS: The findings indicate that continuous planting has led to an increase in the richness and diversity of rhizosphere fungi, while concomitantly resulting in a decrease in the richness and diversity of root fungi. The diversity of endophytic fungal communities in roots was lower than that of the rhizosphere fungi. Ascomycota and Basidiomycota were the dominant phyla detected during the continuous cropping of K. valerianoides. In addition, we found that root rot directly affected the structure and diversity of fungal communities in the rhizosphere and the roots of K. valerianoides. Consequently, both the rhizosphere and endophyte fungal communities of root rot-infected plants showed higher richness than the healthy plants. The relative abundance of Fusarium in two and three years old root rot-infected plants was significantly higher than the control, indicating that continuous planting negatively affected the health of K. valerianoides plants. Decision Curve Analysis showed that soil pH, organic matter (OM), available K, total K, soil sucrase (S_SC), soil catalase (S_CAT), and soil cellulase (S_CL) were significantly related (p < 0.05) to the fungal community dynamics. CONCLUSIONS: The diversity of fungal species in the rhizosphere and root of K. valerianoides was reported for the first time. The fungal diversity of rhizosphere soil was higher than that of root endophytic fungi. The fungal diversity of root rot plants was higher than that of healthy plants. Soil pH, OM, available K, total K, S_CAT, S_SC, and S_CL were significantly related to the fungal diversity. The occurrence of root rot had an effect on the community structure and diversity of rhizosphere and root endophytic fungi.

Complete genome sequence of a novel totivirus isolated from the leaves of Myrica rubra.

Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf apices of Chinese bayberry was identified by transcriptome sequencing and reverse transcription PCR (RT-PCR). The complete genome of the virus was determined to be 4959 nucleotides long, and it contains two open reading frames (ORFs). Its genomic organization is similar to that of previously reported totiviruses. ORF1 encodes a putative coat protein (CP) of 765 aa, and ORF2 encodes an RNA-dependent RNA polymerase (RdRp) of 815 aa. These two putative proteins share 55.1% and 62.6%, amino acid sequence identity, respectively, with the corresponding proteins of Panax notoginseng virus A, respectively. According to the demarcation criteria for totivirus species established by the International Committee on Taxonomy of Viruses (ICTV), the new virus should be considered a member of a new species in the genus totivirus, family Orthototiviridae, which we have tentatively named ''Myrica rubra-associated totivirus'' (MRaTV).

Safety and benefit of modified mesohepatectomy in the treatment of bilobar involvement congenital biliary dilatation.

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.

Efficacy of radiotherapy in combined treatment of hepatocellular carcinoma patients with portal vein tumor thrombus: a real-world study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. METHODS: Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. RESULTS: Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p < 0.05). The residual cancer was significantly more restrictive than that of primary tumor in paired patients based on pathological measurement (p = 0.008). The PCR incidence of the primary tumor (21.42%) was significantly lower (p = 0.008) than that of PVTT in the pathologic study (78.57%). CONCLUSION: PVTT is more sensitive to radiotherapy treatment than the primary tumor in patients with HCC. This combination therapy might be an effective option as a downstaging therapy for patients with HCC with PVTT.

Chemical Constituents, Hypolipidemic, and Hypoglycemic Activities of Edgeworthia gardneri Flowers.

The flowers of Edgeworthia gardneri are used as herbal tea and medicine to treat various metabolic diseases including hyperglycemia, hypertension, and hyperlipidemia. This paper investigate the chemical constituents and biological activities of ethanolic extract and its different fractions from E. gardneri flowers. Firstly, the E. gardneri flowers was extracted by ethanol-aqueous solution to obtain crude extract (CE), which was subsequently fractionated by different polar organic solution to yield precipitated crystal (PC), dichloromethane (DCF), ethyl acetate (EAF), n-butanol (n-BuF), and residue water (RWF) fractions. UHPLC-ESI-HRMS/MS analysis resulted in the identification of 25 compounds, and the main compounds were flavonoids and coumarins. The precipitated crystal fraction showed the highest phenolic and flavonoid contents with 344.4 ± 3.38 mg GAE/g extract and 305.86 ± 0.87 mg RE/g extract. The EAF had the strongest antioxidant capacity and inhibitory effect on α-glucosidase and pancreatic lipase with IC50 values of 126.459 ± 7.82 and 23.16 ± 0.79 µg/mL. Besides, both PC and EAF significantly regulated the glucose and lipid metabolism disorders by increasing glucose consumption and reducing TG levels in HepG2 cells. Molecular docking results suggested that kaempferol-3-O-glucoside and tiliroside had good binding ability with enzymes, indicating that they may be potential α-glucosidase and pancreatic lipase inhibitors. Therefore, the E. gardneri flowers could be served as a bioactive agent for the regulation of metabolic disorders.

Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale.

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features.

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

Complete genome sequence of polygonatum mosaic-associated virus 1, a novel member of the genus Potyvirus in China.

The complete genome sequence of a putative novel potyvirus, tentatively named "polygonatum mosaic-associated virus 1" (PMaV1), was sequenced from naturally infected Polygonatum cyrtonema Hua in China. PMaV1 has a typical genome organization of potyviruses with a single large open reading frame (nt 119-9448) that encodes a 3109-aa polyprotein that is predicted to be cleaved into 10 mature proteins by virus-encoded proteases. Pairwise comparisons revealed that PMaV1 shares 71.50% complete genome sequence identity with Polygonatum kingianum virus 4 and 80.00% amino acid sequence identity with Polygonatum kingianum virus 3 of the genus Potyvirus. Phylogenetic analysis indicated that PMaV1 clustered with other potyviruses and that it was most closely related to Polygonatum kingianum virus 3 and Polygonatum kingianum virus 4. These results suggest that PMaV1 is a new member of the genus Potyvirus of the family Potyviridae (Nucleotide sequence data reported are available in the GenBank databases under the accession number OP380926).

Complete genome sequence analysis of a new potyvirus isolated from Paris polyphylla var. yunnanensis.

The complete genome sequence of a new potyvirus from Paris polyphylla var. yunnanensis was determined. Its genomic RNA consists of 9571 nucleotides (nt), excluding the 3'-terminal poly(A) tail, containing the typical open reading frame (ORF) of potyviruses and encoding a putative large polyprotein of 3061 amino acids. The virus shares 54.20%-59.60% nt sequence identity and 51.80%-57.90% amino acid sequence identity with other potyviruses. Proteolytic cleavage sites and conserved motifs of potyviruses were identified in the polyprotein and within individual proteins. Phylogenetic analysis indicated that the virus was most closely related to lily yellow mosaic virus. The results suggest that the virus should be classified as a member of a novel species within the genus Potyvirus, and we have tentatively named this virus "Paris yunnanensis mosaic chlorotic virus" (PyMCV).

Tandem Mass Spectrometry Imaging Enables High Definition for Mapping Lipids in Tissues.

Mass spectrometry imaging (MSI) of lipids in biological tissues is useful for correlating molecular distribution with pathological results, which could provide useful information for both biological research and disease diagnosis. It is well understood that the lipidome could not be clearly deciphered without tandem mass spectrometry analysis, but this is challenging to achieve in MSI due to the limitation in sample amount at each image spot. Here we develop a multiplexed MS2 imaging (MS2 I) method that can provide MS2 images for 10 lipid species or more for each sampling spot, providing spatial structural lipidomic information. Coupling with on-tissue photochemical derivatization, imaging of 20 phospholipid C=C location isomers is also realized, showing enhanced molecular images with high definition in structure for mouse brain and human liver cancer tissue sections. Spatially mapped t-distributed stochastic neighbor embedding has also been adopted to visualize the tumor margin with enhancement by structural lipidomic information.

The role of CpG island methylator phenotype in the clinical course of hepatocellular carcinoma.

MOTIVATION: Aberrant DNA methylation is strongly associated with heterogeneity in tumors. This study investigated the prognostic value of CpG island methylator phenotype in hepatocellular carcinoma (HCC). RESULTS: A total of 319 HCC samples with 21 121 CpG sites were included in this study and 215 disease-free survival (DFS) and overall survival (OS)-related CpG sites were identified. These CpG sites were divided into seven clusters by using consensus clustering method. Cluster 4, which constructed the prognostic prediction model as the seed cluster to evaluate survival risk for DFS and OS of HCC patients, had the lowest methylation level with the worse prognosis. The low-risk group patients had a significantly prolonged DFS and OS than the patients in the high-risk group (P = 0.008 and P < 0.001, respectively). A receiver operating characteristic curve results for predicting DFS and OS were 0.691 and 0.695, respectively. These results suggested that the CpG site methylation appears to be an informative prognostic biomarker in HCC. The CpG site methylation-related prognostic model may be an innovative insight to evaluate clinical outcomes for HCC patients. AVAILABILITY AND IMPLEMENTATION: The code of the analysis is available at https://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

From liver surgery to liver transplant surgery: new developments in autotransplantation.

PURPOSE OF REVIEW: In spite of substantial technical improvements and conceptual revolutions in advanced liver surgery, there are still straitened circumstances that pose difficulties for in-situ liver resections. Ex-vivo liver resection and autotransplantation (ELRA) is a hybrid technique combining experiences from conventional liver surgery and liver transplantation. This technique is becoming more comprehensive and popular among leading centers recently. RECENT FINDINGS: Short-term and long-term outcomes are now the focus of the technique after more than a decade of cumulative progress and technical evolution. As the 5-year survival nowadays reaches over 80%, this technique is believed to be beneficial for advanced tumors. In recent years, ELRA has been applied by more centers on larger scales, and the learning curve was set at 53 cases. Progresses in disease selection, surgical indications, individualized outflow reconstruction, or autograft implantation, management of co-morbidities (e.g., Budd-Chiari syndrome, caval and/or neighboring organ involvements, obstructive jaundice) propelled the development of the technique. SUMMARY: This hybrid liver surgery will benefit for carefully selected patients presented with advanced benign diseases and well-differentiated malignancies.

Parasite Circulating Cell-free DNA in the Blood of Alveolar Echinococcosis Patients as a Diagnostic and Treatment-Status Indicator.

BACKGROUND: Alveolar echinococcosis (AE) is a serious parasitic disease caused by the larvae of Echinococcus multilocularis. It is the less common but substantially more deadly of the 2 major echinococcosis diseases that can occur globally but are concentrated in central Asia. METHODS: We analyzed parasite circulating cell-free DNA (cfDNA) in 149 plasma samples using a DNA sequencing-based method (105 AE, 16 cystic echinococcosis, 4 liver cancer, 4 gallstones, and 20 healthy volunteers). After identifying the Echinococcus-specific cfDNA (Em-cfDNA) sequences in the samples, we determined whether Em-cfDNA could be used for AE diagnosis and as a potential indicator of the effectiveness of surgical treatment. We also examined potential associations between Em-cfDNA levels and clinical features of AE patients. RESULTS: Our work demonstrates that varying reads of Em-cfDNA were detectable in the plasma of 100% of preoperative AE patients and that all of the non-AE patients and healthy volunteers were negative. Em-cfDNA has good sensitivity and specificity for the diagnosis of AE. We also found that Em-cfDNA levels apparently have reference value for evaluating the therapeutic efficacy of surgery interventions for AE lesions. Finally, our analysis revealed that Em-cfDNA levels can reflect meaningful information about lesion size in preoperative AE patients. CONCLUSIONS: We demonstrate that sequencing-based monitoring of Em-cfDNA can be used in the clinic as a powerful diagnostic indicator for AE. We also note that there is a strong potential for use of this liquid-biopsy method to monitor ongoing disease status in postintervention AE patients.

CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma.

Unlike hematological malignancies, solid tumors have proved to be less susceptible to chimeric antigen receptor (CAR)-T cell therapy, which is partially caused by reduced accumulation of therapeutic T cells in tumor site. Since efficient trafficking is the precondition and pivotal step for infused CAR-T cells to exhibit their anti-tumor function, strategies are highly needed to improve the trafficking ability of CAR-T cells for solid tumor treatment. Here, based on natural lymphocyte chemotaxis theory and characteristics of solid tumor microenvironments, we explored the possibility of enhancing CAR-T cell trafficking by using chemokine receptors. Our study found that compared with other chemokines, several CXCR2 ligands showed relatively high expression level in human hepatocellular carcinoma tumor tissues and cell lines. However, both human peripheral T cells and hepatocellular carcinoma tumor infiltrating T cells lacked expression of CXCR2. CXCR2-expressing CAR-T cells exhibited identical cytotoxicity but displayed significantly increased migration ability in vitro. In a xenograft tumor model, we found that expressing CXCR2 in CAR-T cells could significantly accelerate in vivo trafficking and tumor-specific accumulation, and improve anti-tumor effect of these cells.

Preoperative Remnant Liver Function Evaluation Using a Routine Clinical Dynamic Gd-EOB-DTPA-Enhanced MRI Protocol in Patients with Hepatocellular Carcinoma.

BACKGROUND: To investigate the clinical feasibility of preoperative routine clinical dynamic Gd-EOB-DTPA-enhanced MRI alone to predict post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: 116 patients with HCC who underwent liver resection in Southwest Hospital from 2014 through 2017 were selected in this retrospective cohort study. The remnant function (RF) of the liver RFUR and RFRE15 were calculated by the sum of the uptake rate (UR) or relative enhancement at 15 min (RE15) from dynamic Gd-EOB-DTPA-enhanced MR images in the remnant liver regions, and standardized by standard liver volume (SLV) to generate sRFUR (standardized RFUR) and sRFRE15 (standardized RFRE15). Student's t test or Mann-Whitney U test, logistic regression, and ROC analyses were used to test the associations of preoperative RFUR, sRFUR, RFRE15, sRFRE15, the remnant liver volume (RLV)/SLV, ICG retention rate at 15 min (ICG R15) and sRFICG-K [ICG clearance rate (ICG-K) × RLV/SLV] with PHLF. RESULTS: 28 patients were found to have PHLF, who showed lower RFUR, sRFUR, RFRE15, sRFRE15, RLV/SLV, sRFICG-K, and higher ICG R15 than patients without PHLF (p < 0.001 for all). After adjusting for clinical parameters, RFUR (p = 0.001), sRFUR (p = 0.001), RFRE15 (p = 0.002), or sRFRE15 (p = 0.003) was found to be independently significant indicator in multivariable logistic regression, respectively. RFUR (0.882) and sRFUR (0.882) had larger AUCs than RLV/SLV (0.731, p = 0.008; p = 0.005), ICG R15 (0.765, p = 0.039; p = 0.044) and sRFICG-K (0.767, p = 0.031; p = 0.023). RFRE15 (0.845) and sRFRE15 (0.839) had larger AUCs than RLV/SLV (0.731, p = 0.027; p = 0.025). CONCLUSIONS: The remnant liver function parameters preoperatively estimated from a routine clinical dynamic Gd-EOB-DTPA-enhanced MRI protocol can predict PHLF in patients with HCC, and may be better predictors than conventional methods.

AI-assisted CT imaging analysis for COVID-19 screening: Building and deploying a medical AI system.

The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hope artificial intelligence (AI) to reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. In this paper, we present our experience in building and deploying an AI system that automatically analyzes CT images and provides the probability of infection to rapidly detect COVID-19 pneumonia. The proposed system which consists of classification and segmentation will save about 30%-40% of the detection time for physicians and promote the performance of COVID-19 detection. Specifically, working in an interdisciplinary team of over 30 people with medical and/or AI background, geographically distributed in Beijing and Wuhan, we are able to overcome a series of challenges (e.g. data discrepancy, testing time-effectiveness of model, data security, etc.) in this particular situation and deploy the system in four weeks. In addition, since the proposed AI system provides the priority of each CT image with probability of infection, the physicians can confirm and segregate the infected patients in time. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we are able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases.

Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?

OBJECTIVE: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. SUMMARY/BACKGROUND: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. METHODS: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. RESULTS: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. CONCLUSIONS: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Deep Convolutional Neural Network-Aided Detection of Portal Hypertension in Patients With Cirrhosis.

BACKGROUND & AIMS: Noninvasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. METHODS: We collected liver and spleen images from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient of 10 mm Hg or higher. In total, we analyzed 10,014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45,554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then sampled randomly and equiprobably for 6 times into training, validation, and test data sets (ratio, 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. RESULTS: The CT-based CNN analysis identified patients with CSPH with an area under the receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996-1.000), an AUC of 0.912 in the validation set (95% CI, 0.854-0.971), and an AUC of 0.933 (95% CI, 0.883-0.984) in the test data sets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999-1.000), an AUC of 0.924 in the validation set (95% CI, 0.833-1.000), and an AUC of 0.940 in the test data set (95% CI, 0.880-0.999). When the model development procedures were repeated 6 times, AUC values for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P > .05). CONCLUSIONS: We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a noninvasive and rapid method for detection of CSPH (ClincialTrials.gov numbers: NCT03138915 and NCT03766880).

Characterization of a New Orthotospovirus from Chilli Pepper in Yunnan Province, China.

Chilli pepper (Capsicum annuum L.) is one of the most important crops in Yunnan Province, China. An orthotospovirus isolate 14YV855 was isolated from a diseased chilli pepper plant exhibiting yellow ringspots and necrosis on leaves in Shiping County, Honghe Hani and Yi Autonomous Prefecture, Yunnan Province in 2014. The complete genome sequence of 14YV855 was determined. The small, medium, and large RNAs are 3,428, 4,781, and 8,917 nucleotides long, respectively. The complete nucleocapsid (N) protein of 14YV855 shares a high amino acid identity of 84.8 to 89.9% to that of Capsicum chlorosis virus (CaCV), Groundnut bud necrosis virus (GBNV), Watermelon bud necrosis virus (WBNV), and Watermelon silver mottle virus (WSMoV), which is slightly less than the 90% identity threshold for the demarcation of new Orthotospovirus sp. Phylogenetic analyses revealed that the N protein and RNA-dependent RNA polymerase of 14YV855 are the most related to WSMoV, while the NSs, NSm, and Gn/Gc proteins are similar to those of GBNV. As expected, 14YV855 is serologically related to CaCV, GBNV, WBNV, and WSMoV when the monoclonal antibody against the N protein of WSMoV was used; however, 14YV855 can be distinguished from other orthotospoviruses by reverse-transcription PCR using the specific primers. Our results indicate that 14YV855 is a new Orthotospovirus sp. belonging to the WSMoV serogroup and is provisionally named Chilli yellow ringspot virus.

Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP.

A majority of hepatocellular carcinomas (HCCs) combine with liver cirrhosis. The cirrhotic liver has been implicated in interfering with the effects of HCC-targeted drugs, including sorafenib. Alterations in the tumor microenvironment of the cirrhotic liver include both biochemical and biomechanical factors. In this study, we induced sorafenib resistance in HCC cells. We observed changes in cell morphology, cytoskeletal architecture, and cellular stiffness in these sorafenib-resistant cells, resembling those adapted to stiffer substrates. To examine the contribution of mechanical factors in HCC cell growth and drug resistance, we used an in vitro cell culture system with adjustable stiffness mimicking the normal or cirrhotic liver tissues. We identified that mechanical adaptation conferred HCC cells with increased motility and sorafenib resistance. We further reported the mechanism underlying the involvement of the transcription coactivator YAP. Our results underline the important role of mechanical factors in the interaction between tumor cells and their microenvironment.