Genome-wide identification of Rosa roxburghii CML family genes identifies an RrCML13-RrGGP2 interaction involved in calcium-mediated regulation of ascorbate biosynthesis.

Calmodulin-like proteins (CMLs) are an essential family of calcium sensors involved in multiple Ca2+-mediated cellular processes in plants. Rosa roxburghii Tratt, known for the abundance of L-ascorbic acid (AsA) in its fruits, is widely distributed in calcium-rich soil of the karst region in southwestern China. The aim of this study was to identify key CMLs that respond to exogenous Ca2+ levels and regulate AsA biosynthesis in R. roxburghii. A genome-wide scan revealed the presence of 41 RrCML genes with 1-4 EF-hand motif (s) unevenly distributed across the 7 chromosomes of R. roxburghii. qRT-PCR analysis revealed that RrCML13, RrCML10, and RrCML36 responded significantly to exogenous Ca2+ treatment, and RrCML13 was positively correlated with GDP-L-galactose phosphorylase encoding gene (RrGGP2) expression and AsA content in the developing fruit. Overexpression of RrCML13 in fruits and roots significantly promoted the transcription of RrGGP2 and the accumulation of AsA, while virus-induced silencing of RrCML13 reduced the transcription of RrGGP2 and the content of AsA. Furthermore, Moreover, the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) analysis confirmed the interaction between RrCML13 and RrGGP2 proteins, indicating that RrCML13 plays a regulatory role in calcium-mediated AsA biosynthesis. This study enhances our understanding of R. roxburghii CMLs and sheds light on the calcium-mediated regulation of AsA biosynthesis.

CT radiomics combined with clinical and CT features for predicting TNM stage of thymic epithelial tumor / 中国介入影像与治疗学

Objective To explore the value of CT radiomics combined with clinical data and CT features for predicting TNM stage of thymic epithelial tumor(TET).Methods Data of 216 single TET patients confirmed by surgical pathology were retrospectively analyzed.Totally 151 cases with TNM stage Ⅰ TET were divided into early group,while 27 with TNM stage Ⅲ and 38 with TNM stage Ⅳ TET were divided into late group(n=65).Univariate analysis was used to analyze clinical data and chest CT manifestations.Based on non-contrast-enhanced CT(NECT)and contrast-enhanced CT(CECT),the best radiomics features were extracted and screened to establish radiomics models(RMNECT,RMCECT)for predicting TNM stage of TET.RMNECT-clinic,RMCECT-clinic,RMNECT-clinic-CT and RMCECT-clinic-CT were constructed based on combination of clinical and CT features being significantly different between groups,respectively.The patients were divided into training set(n=151)and validation set(n=65)at the ratio of 7∶3.The above models were trained in the training set using repeated 5-fold cross validation method,and their efficacy were verified in the validation set.Results Significant differences of clinical symptoms and CT manifestations including fat infiltration around the lesion,mediastinal lymph node enlargement and pleural effusion were found between groups(all P＜0.05).Based on NECT and CECT,2 and 9 best radiomics features were selected to construct the corresponding models.In validation set,the area under the curve(AUC)of RMNECT-clinic-CT for predicting TNM stage of TET(0.864)was higher than that of RMNECT and RMNECT-clinic(AUC=0.634,0.721,Z=3.081,2.937,P=0.002,0.003),while AUC of RMCECT-clinic-CT(0.920)was also higher than that of RMCECT and RMCECT-clinic(AUC=0.689,0.751,Z=2.698,2.390,P=0.007,0.017).Conclusion CT radiomics combined with clinical data and CT features could effectively predict TNM stage of TET.

The complete chloroplast genome of Allium wallichii Kunth (Amaryllidaceae).

Allium wallichii Kunth is a herb species with potentially extensive applications because of its edible, ornamental, and pharmaceutical values. The structural characteristics and phylogenetic relationships of its chloroplast genome were determined here for the first time. The complete cp genome was found to be 152,496 bp long, with a GC content of 37.04%. It consists of four distinct regions: a large single copy (LSC) region of 82,510 bp, a small single copy (SSC) region of 17,460 bp, and two inverted repeat (IR) regions of 26,263 bp each. The genome encodes 129 genes, including 86 protein-coding genes, 37 tRNA genes, and six rRNA genes. Our phylogenetic analysis revealed that A. wallichii was closely related to Allium wallichii var. platyphyllum, which are included in the section Bromatorrhiza, subgenus Amerallium Traub of the genus Allium. Our report provides valuable information on the genetic diversity of Allium species.

Prediction of Lymph Node Metastasis of Mixed Ground-glass Nodules Based on Clinical Imaging Information / 中国肺癌杂志

BACKGROUND@#Previous studies have shown that lymph node metastasis only occurs in some mixed ground-glass nodules (mGGNs) which the pathological results were invasive adenocarcinoma (IAC). However, the presence of lymph node metastasis leads to the upgrading of tumor-node-metastasis (TNM) stage and worse prognosis of the patients, so it is important to perform the necessary evaluation before surgery to guide the operation method of lymph node. The aim of this study was to find suitable clinical and radiological indicators to distinguish whether mGGNs with pathology as IAC is accompanied by lymph node metastasis, and to construct a prediction model for lymph node metastasis.@*METHODS@#From January 2014 to October 2019, the patients with resected IAC appearing as mGGNs in computed tomography (CT) scan were reviewed. All the lesions were divided into two groups (with lymph node metastasis or not) according to their lymph node status. Lasso regression model analysis by applying R software was used to evaluate the relationship between clinical and radiological parameters and lymph node metastasis of mGGNs.@*RESULTS@#A total of 883 mGGNs patients were enroled in this study, among which, 12 (1.36%) showed lymph node metastasis. Lasso regression model analysis of clinical imaging information in mGGNs with lymph node metastasis showed that previous history of malignancy, mean density, mean density of solid components, burr sign and percentage of solid components were informative. Prediction model for lymph node metastasis in mGGNs was developed based on the results of Lasso regression model with area under curve=0.899.@*CONCLUSIONS@#Clinical information combined with CT imaging information can predict lymph node metastasis in mGGNs.

Abdominal contrast-enhanced CT for diagnosing and transcatheter arterial embolization for treating spontaneous retroperitoneal hematoma / 中国介入影像与治疗学

Objective To observe the value of abdominal contrast-enhanced CT for diagnosis of spontaneous retroperitoneal hematoma(SRH)and transcatheter arterial embolization for treating SRH.Methods Data of 7 SRH patients were retrospectively analyzed,including 4 cases diagnosed with abdominal contrast-enhanced CT,1 case diagnosed with plain CT and 2 cases diagnosed with abdominal ultrasound.Transcatheter angiography was performed to explore the offending artery of SRH which were then treated with trancatheter arterial embolization.The total angiographic time,i.e.the time span between the first and the last angiography was recorded and the treatment effect was observed.Results Among 7 patients,the offending artery of SRH was identified and embolized,and 30 days follow-up showed stable condition in 6 cases.The offending artery of SRH was not found in 1 case who then received conservative medical treatment,and the condition remained stable.The total angiographic time in 4 cases diagnosed with abdominal contrast-enhanced CT were 32-60 min,with a median time of 47.5 min,while in the rest 3 were 36-80 min,with a median time of 63.0 min.Conclusion Abdominal contrast-enhanced CT was helpful to diagnosis and displaying the offending artery of SRH.Transcatheter arterial embolization was effective for treating SRH.

Lung Imaging Evaluation in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation / 中国医学影像学杂志

Purpose To analyze the abnormal CT imaging features of the lungs of adult patients with chronic graft-versus-host disease(cGVHD)and to improve the ability of diagnosis and differentiation of abnormal cGVHD lungs via combining with clinical data.Materials and Methods A retrospective study of 162 patients with clinical manifestations of cGVHD after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital from October 2018 to October 2020 was conducted.The chest CT images(including lesion location,distribution,ground glass density,consolidation,mesh image,nodule image,bronchiectasis,pleural effusion,gas retention,pneumothorax or mediastinal air)were summarized and the differences of imaging features between pulmonary cGVHD and pulmonary infection were compared.Results Of the 50 fungal infections,43 had single nodules;of the 7 viral infections,4 had diffuse ground glass nodules;2 had diffuse grid shadows,and of the 5 bacterial infections,1 had limited solid shadows.The 36 cases of non-infectious pulmonary complications were all oblusive bronchiolitis,and the CT signs showed gas retention in 32 cases,bronchiectasis in 22 cases,and thickening of the bronchial wall in 27 cases.Conclusion The vast majority of cGVHD patients have abnormal lung imaging,with the main cause of infection.Some patients have imaging manifestations of obliterated bronchiolitis,and imaging combined with clinical practice may be helpful for the diagnosis and differentiation of lung complications.

Genome-Wide Identification, Expression and Interaction Analysis of GmSnRK2 and Type A PP2C Genes in Response to Abscisic Acid Treatment and Drought Stress in Soybean Plant.

As a typical ancient tetraploid, soybean (Glycine max) is an important oil crop species and plays a crucial role in supplying edible oil, plant protein and animal fodder worldwide. As global warming intensifies, the yield of soybean in the field is often strongly restricted by drought stress. SNF1-related protein kinase 2 (SnRK2) and type A protein phosphatase 2C (PP2C-A) family members are core components of the abscisic acid (ABA) signal transduction pathway in plants and have been suggested to play important roles in increasing plant tolerance to drought stress, but genetic information supporting this idea is still lacking in soybean. Here, we cloned the GmSnRK2s and GmPP2C-A family genes from the reference genome of Williams 82 soybean. The results showed that the expression patterns of GmSnRK2s and GmPP2C-As are spatiotemporally distinct. The expression of GmSnRK2s in response to ABA and drought signals is not strictly the same as that of Arabidopsis SnRK2 homologous genes. Moreover, our results indicated that the duplicate pairs of GmSnRK2s and GmPP2C-As have similar expression patterns, cis-elements and relationships. GmSnRK2.2 may have a distinct function in the drought-mediated ABA signaling pathway. Furthermore, the results of yeast two-hybrid (Y2H) assays between GmSnRK2s and GmPP2C-As revealed that GmSnRK2.17, GmSnRK2.18, GmSnRK2.22, GmPP2C5, GmPP2C7, GmPP2C10 and GmPP2C17 may play central roles in the crosstalk among ABA signals in response to drought stress. Furthermore, GmPP2C-As and GmSnRKs were targeted by miRNA and validated by degradome sequencing, which may play multiple roles in the crosstalk between ABA and drought signals and other stress signals. Taken together, these results indicate that GmSnRK2s and GmPP2C-As may play a variety of roles in the drought-mediated ABA signaling pathway.

The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis.

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

Value of the deep learning image reconstruction algorithm combined with low-kV technique in improving small vessel display level at routine abdominal contrast enhanced CT imaging / 中华放射学杂志

Objective:To evaluate the presentation of small arteries in abdominal contrast-enhanced CT late-arterial images using the deep learning image reconstruction (DLIR) combined with low tube voltage (kV) technique relative to the adaptive statistical iterative reconstruction V (ASiR-V) algorithm.Methods:Patients who were admitted to Peking University People′s Hospital from December 2021 to January 2022 and needed to be screened for abdominal diseases and receive abdominal and pelvic contrast-enhanced CT scan were prospectively collected. The patients were divided into low-voltage (LV) with 80 kV and high-voltage (HV) with 120 kV groups. According to two different reconstruction algorithms, each group was further divided into DLIR-H (D) subgroup and ASiR-V 50% (A) subgroup. The automatic tube current adjustment technique was used for CT enhanced scanning of patients, and the noise index value was uniformly set to 9. Subjective and objective evaluations were performed on the late-arterial images with a constructed slice thickness of 0.625 mm, and the radiation doses were recorded.Results:A total of 168 patients were included, including 76 males and 92 females, aged 18-85 (53±15) years old, body mass index (24±3) kg/m 2; 91 patients in the LV group and 77 in the HV group. The CT values of the aorta and common hepatic artery in the LV group were significantly higher than those in the HV group ( t=-14.20, P<0.001; t=-0.95, P<0.001). When the tube voltage was the same, the late-arterial image noise in subgroup D was significantly lower than that in subgroup A, and the signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the liver, aorta and common hepatic artery were significantly higher than those in subgroup A (all P<0.001). The SNR and CNR of the aorta and common hepatic artery in the LV-D subgroup were significantly better than those in the LV-A, HV-D, and HV-A subgroups (all P<0.001). In the subjective evaluation of abdominal vascular display, the special resolution of the common hepatic artery, inferior mesenteric artery and the edge of the ascending branch of the left colic artery, and the contrast of the ascending branch of the left colic artery in the LV-D subgroup were significantly better than those of the LV-A, HV-D, and HV-A subgroups ( P<0.05). Moreover, the presentation rate of margin artery of splenic region (54.9%, 50/91) in the LV-D subgroup was significantly higher than those in the HV-D subgroup (24.7%, 19/77) and HV-A subgroup (32.5%, 25/77) (adjusted P<0.05). There was no significant difference in the radiation doses between LV and HV groups [(4.91±1.97) mSv vs (5.43±1.78) mSv, P>0.05]. Conclusion:The contrast-enhanced CT scan of abdomen with low tube voltage combined with DLIR algorithm can effectively improve the display level of the ascending vessel of left colonic artery from the inferior mesenteric artery and the margin artery, which brings more possibilities for the evaluation of similar small blood vessels.

Analysis of disease free survival based on CT imaging features in patients with cN0 gastric cancer / 中华放射学杂志

Objective:To explore CT imaging features related to disease-free survival (DFS) for gastric cancer (GC) patients with no clinical lymph node metastasis (cN0).Methods:From January 2005 to December 2018, 298 patients with GC were collected retrospectively in Peking University People′s Hospital. All the patients performed CT scanning before operation, and cT1-4N0M0 was defined by CT images. The clinical tumor stage (cT), extramural vessel invasion (EMVI), tumor morphological type, location and size were defined and recorded based on preoperative contrast-enhanced CT images. According to the pathological results, the patients were divided into pT1-2, pT3-4, pN0, and pN1-3 subgroups, with 148, 150, 135, and 163 cases, respectively. Progressive events and corresponding time were recorded during follow-up. DFS was defined as the time from radical operation to progressive events; if no progressive events occurred, DFS was defined as the time from radical operation to the last follow-up. The Kaplan-Meier curve and log-rank test were used to analyze the differences in cumulative DFS among patients with different CT imaging features, and Cox survival analysis was used to explore the independent CT imaging risk factors affecting DFS of cN0 patients. The log-rank test was used to test the effect of independent risk factors on cumulative DFS in different subgroups.Results:The follow-up time of enrolled patients was 36.0 (14.9, 59.3) months. The 3-year cumulative DFS rates of cT3-4 and cT1-2 GC patients were 61.2% and 85.6%, respectively, and the difference of DFS was statistically significant (χ 2=22.72, P<0.001). The 3-year cumulative DFS rate of EMVI-positive patients was 46.3%, which was lower than that of EMVI-negative patients (77.1%), and the difference was statistically significant (χ 2=21.34, P<0.001). There was no significant difference in 3-year cumulative DFS between different tumor locations and morphological types (χ 2=1.75, 1.73, P=0.189, 0.196). The difference in 3-year cumulative DFS between the tumor maximal diameter ≥3.4 cm and <3.4 cm groups was statistically significant (χ 2=17.58, P<0.001). On Cox survival analysis, cT (HR=5.203, P=0.001) and EMVI (HR=1.971, P=0.025) were independent risk factors for 3-year DFS in patients with cN0 GC. The results of subgroup analysis showed that the effect of EMVI on the 3-year DFS in pN0, pN1-3, pT1-2 and pT3-4 subgroups was statistically significant ( P<0.05). The effect of cT on the 3-year DFS was statistically significant in pN0, pN1-3, and pT1-2 subgroups ( P<0.05), but not in pT3-4 group (χ 2=2.58, P=0.108). Conclusion:cT and EMVI defined on preoperative CT examination are independently prognostic factors of 3-year DFS for patients with cN0 GC.

One case of bloodstream infection caused by Ureaplasma urealyticum / 中国热带医学

@#Abstract: Objective To analyze a case of bloodstream infection caused by Ureaplasma urealyticum after abortion in Anxi County Hospital, so as to provide basis for the clinical diagnosis and treatment. Methods　The diagnosis of Ureaplasma urealyticum in this patient with bloodstream infection was retrospectively analyzed. The basic clinical data and laboratory diagnosis data were collected, including the characteristics of blood culture curve, Wright staining of culture medium, drug sensitivity of Mycoplasma liquid identification, colony characteristics of solid medium, and the conclusion of targeted DNA sequencing. Through the comprehensive analysis of the above data, the rapid diagnosis of this case can be realized by optimizing the detection and diagnosis process. Results　The clinical manifestations of this patient were fever of 38.5 ℃, CRP:14.85 mg/L, WBC:14.33×109/L, NET: 85.40%, PCT: 0.12 ng/mL, IL-6: 665.6 pg/mL, positive after 3 days of blood culture, no bacteria were found in Gram stain, and sand-like purple bacteria were observed after adding Wright's stain. After inoculation in blood agar, Mycoplasma solid and liquid medium, no colonies were grown in blood agar, after 48 h and 5 d. On Mycoplasma A7 agar, the edge of brown fried egg colony was striature, and it could be identified as Ureaplasma urealyticum with the Mycoplasma ID & AST panel, which was resistant to quinolones and spectinomycin, but sensitive to macrolides, tetracyclines and lincomycin. Subsequent targeted DNA sequencing results were also confirmed for Ureaplasma urealyticum. Before receiving the report, clinical experience treatment with ceftriaxone metronidazole was used to fight infection with negative bacilli and anaerobic bacteria. Mycoplasma was not treated with targeted treatment. After 3 days, the patient's body temperature returned to normal, inflammation index decreased, and the patient asked to be discharged. Conclusions　At present, there are few reports of bloodstream infection caused by Ureaplasma urealyticum, and the lack of clinical understanding can easily lead to misdiagnosis and missed diagnosis. In order to improve the detection rate of Mycoplasma in blood culture, it is necessary to optimize the detection procedure of blood culture and provide accurate diagnosis and treatment basis for clinical practice. However, it is clear from this case that Mycoplasma bloodstream infection cases are self-limited infection and can recover by themselves without targeted treatment in patients with normal immunity. Therefore, it is very important to protect the immunity of patients.

Genome-Wide Analysis of Dof Genes and Their Response to Abiotic Stress in Rose (Rosa chinensis).

Dof (DNA binding with one finger) proteins play important roles in plant development and defense regulatory networks. In the present study, we report a genome-wide analysis of rose Dof genes (RchDof), including phylogenetic inferences, gene structures, chromosomal locations, gene duplications, and expression diversity. A total of 24 full-length RchDof genes were identified in Rosa chinensis, which were assigned to nine distinct subgroups. These RchDof genes were unevenly distributed on rose chromosomes. The genome-scale analysis of synteny indicated that segmental duplication events may have played a major role in the evolution of the RchDof gene family. Analysis of cis-acting elements revealed putative functions of Dofs in rose during development as well as under numerous biotic and abiotic stress conditions. Moreover, the expression profiles derived from qRT-PCR experiments demonstrated distinct expression patterns in various tissues, and gene expression divergence existed among the duplicated RchDof genes, suggesting a fundamentally functional divergence of the duplicated Dof paralogs in rose. The gene expression analysis of RchDofs under drought and salt stress conditions was also performed. The present study offered novel insights into the evolution of RchDofs and can aid in the further functional characterization of its candidate genes.

Mistletoe Extract Targets the STAT3-FOXM1 Pathway to Induce Apoptosis and Inhibits Metastasis in Breast Cancer Cells.

Mistletoe extracts (Viscum album L.) have been widely used as complementary and alternative medicines for the treatment of cancer, and their cytotoxic effects have been reported on various types of cancer. However, the molecular targets of mistletoe extracts have not been well studied. Herein, we investigated molecules associated with the in vitro and in vivo anticancer effects of mistletoe extract using 4T1 murine breast cancer cells. Mistletoe extract induced apoptosis and inhibited the signal transducer and activator of transcription3 (STAT3) phosphorylation. This inhibition was accompanied by the downregulations of forkhead box M1 (FOXM1) and the DNA repair proteins, RAD51 and survivin. Mistletoe extract simultaneously increased the expression of the DNA damage marker proteins, phosphorylated H2A histone family member X (H2A.X), and phosphorylated p38. Furthermore, mistletoe extract effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition to tumor growth inhibition, mistletoe extract inhibited lung metastasis in the tumor-bearing mice and cell invasiveness by downregulating the expressions of matrix metalloproteinases (MMPs), urokinase-type plasminogen activator (uPA), uPA receptor, and markers of epithelial-mesenchymal transition (snail and fibronectin). Taken together, our results suggest that mistletoe extract targets the STAT3-FOXM1 pathway for its cytotoxic effects, and that mistletoe extracts might be useful for the treatment of patients with cancers highly expressing the STAT3-FOXM1 pathway.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

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The effects of 20%-40% fertilizer reduction and different organic fertilizers on soil microbial biomass, enzyme activity and cotton yield were examined for three consecutive years in Hexi area of Gansu, Northwest China. The results showed that compared with single chemical fertilizer application, the abundance of soil bacteria and actinomycetes were significantly increased while that of fungi were decreased with chemical fertilizer reduction combined with organic fertilizer. The abundance of soil bacteria was maximum under the treatment of chemical fertilizer reduction combined with common organic fertilizer and bio-organic fertilizer (COBF2), which was 84.6%, 57.1% and 43.5% higher than that under single application of chemical fertilizer (CF) in the bud stage, boll stage and boll open stage, while the abundance of actinomycetes was maximum under the chemical fertilizer reduction combined with common bio-organic fertilizer (CBF2), which was 28.2%, 32.7% and 32.2% higher than CF. The abundance of fungi was the lowest in the CBF2 treatment, which was 35.8%, 29.3%and 13.4% lower than CF treatment in three periods. The ratios of bacteria to fungi, actinomycetes to fungi and the activity of soil urease, catalase, sucrase and alkaline phosphatase were increased by the chemical fertilizer reduction combined with organic fertilizer. COBF2 was the most effective way to improve enzyme activity. Fertilizer reduction combined with the application of organic fertilizer increased boll number per individual of cotton plant, promoted cotton growth and dry matter accumulation in the ground to a certain extent. The cotton yield under COBF2 treatment was the highest, which showed an significant increase of 14.2% and 10.9% respectively in seed and lint cotton yield than CF. Our results showed that COBF2, with 60% reduction of chemical fertilizer combined with 1800 kg·hm-2 ordinary organic fertilizer and 600 kg·hm-2 biological organic fertilizer, had the best fertilization effect.

The Chromosome-Based Rubber Tree Genome Provides New Insights into Spurge Genome Evolution and Rubber Biosynthesis.

The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the ∼1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by ∼65.88% (∼970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains ∼15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.

Genome-Wide Analysis of WRKY Genes and Their Response to Hormone and Mechanic Stresses in Carrot.

The WRKY gene family plays a vital role in plant development and environment response. Although previous studies suggested that the WRKY genes in carrot (Kuroda type) involved in biotic and abiotic stress responses, the information of WRKY genes in the latest version of the carrot genome (Daucus carota v2.0, Nantes type carrot) and their response to hormone and injury stresses have not been reported. In this study, we performed a genome-wide analysis of WRKYs using a chromosome-scale genome assembly of carrot (Daucus carota subsp. sativus L.). We identified a total of 67 WRKY genes, which were further classified into the three groups. These WRKY genes are unevenly distributed on carrot chromosomes. We found that more than half of them were derived from whole-genome duplication (WGD) events, suggesting that WGDs have played a major role during the evolution of the WRKY gene family. We experimentally ascertained the expression divergence existed between WGD-derived WRKY duplicated gene pairs, which is indicative of functional differentiation between duplicated genes. Our analysis of cis-acting elements indicated that WRKY genes were transcriptionally regulated upon hormone and mechanic injury stresses. Gene expression analyses by qRT-PCR further presented that WRKY genes were involved in hormone and mechanic injury stresses.

Metformin selectively targets 4T1 tumorspheres and enhances the antitumor effects of doxorubicin by downregulating the AKT and STAT3 signaling pathways.

Recent studies have reported that metformin (Met), the first-line medication for the treatment of type 2 diabetes, exhibited anticancer and chemoprotective effects in diverse cancer cells. In this study, we investigated the effects of Met on the drug-resistance of 4T1 murine breast cancer tumorspheres (TS) and the mechanism responsible for its drug-resistance. 4T1 TS exhibited accumulations of cells at the G0/G1 phase compared with cells in monolayer culture, which suggested the majority of cells in TS were quiescent. Furthermore, it was identified that activations of the signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) signaling pathways in 4T1 TS conferred drug-resistance to doxorubicin (Dox) and lapatinib (Lapa). However, Met selectively targeted TS rather than cells in monolayer culture and increased the cytotoxic effect of Dox on TS by inhibiting activations of the STAT3 and AKT signaling pathways. These observations suggested that inhibitions of STAT3 and AKT underlie the selective cytotoxic effects of Met on TS. In addition, Met exhibited synergistic antitumor effects with Dox on 4T1 tumor-bearing BALB/c mice. Our findings suggest that combinations of Met and cytotoxic anticancer drugs may offer an advantage for treating drug-resistant breast cancer.

Nonpyrolyzed Fe-N Coordination-Based Iron Triazolate Framework: An Efficient and Stable Electrocatalyst for Oxygen Reduction Reaction.

Pyrolyzed base-metal-based metal-organic frameworks (MOFs) with FeNx coordination are emerging as nonprecious metal catalysts for electrochemical oxygen reduction reaction (ORR). However, surprisingly, nonpyrolyzed MOFs involving Fe-N coordination have not been explored for the ORR. This study concerns the catalytic performance of a semiconducting nonpyrolyzed iron triazolate framework (FeTa2 ) for ORR in alkaline electrolyte. The FeTa2 catalyst is studied as composites with different amounts of conductive Ketjenblack carbon (KB). The performance of these FeTa2 -x KB (x denotes the KB/FeTa2 weight ratio) composites by onset and half-wave potentials of ORR appears to be superior to most previously documented nonpyrolyzed MOFs. Characterization by elemental analysis, FTIR spectroscopy, XPS, and cyclic voltammetry suggest that N-FeIII -OH- sites at the surface of FeTa2 function as the catalytic active sites. This FeTa2 also shows very stable activity during ORR, as supported by accelerated durability test of the FeTa2 -x KB sample (20 000 cycles, ca. 90 h). The framework structure of FeTa2 remains intact during the durability test, which would help to explain its excellent catalytic durability. This would be the first study demonstrating efficient and stable ORR catalysis by a nonpyrolyzed Fe-N coordination-based MOF material.