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Abstract Background IDH1-wildtype glioblastoma multiforme (IDHwt-GBM) is a highly heterogeneous and aggressive brain tumour characterised by a dismal prognosis and significant challenges in accurately predicting patient outcomes. To address these issues and personalise treatment approaches, we aimed to develop and validate robust multiomics molecular subtypes of IDHwt-GBM. Through this, we sought to uncover the distinct molecular signatures underlying these subtypes, paving the way for improved diagnosis and targeted therapy for this challenging disease. Methods To identify stable molecular subtypes among 184 IDHwt-GBM patients from TCGA, we used the consensus clustering method to consolidate the results from ten advanced multiomics clustering approaches based on mRNA, lncRNA, and mutation data. We developed subtype prediction models using the PAM and machine learning algorithms based on mRNA and MRI data for enhanced clinical utility. These models were validated in five independent datasets, and an online interactive system was created. We conducted a comprehensive assessment of the clinical impact, drug treatment response, and molecular associations of the IDHwt-GBM subtypes. Results In the TCGA cohort, two molecular subtypes, class 1 and class 2, were identified through multiomics clustering of IDHwt-GBM patients. There was a significant difference in survival between Class 1 and Class 2 patients, with a hazard ratio (HR) of 1.68 [1.15–2.47]. This difference was validated in other datasets (CGGA: HR = 1.75[1.04, 2.94]; CPTAC: HR = 1.79[1.09–2.91]; GALSS: HR = 1.66[1.09–2.54]; UCSF: HR = 1.33[1.00–1.77]; UPENN HR = 1.29[1.04–1.58]). Additionally, class 2 was more sensitive to treatment with radiotherapy combined with temozolomide, and this sensitivity was validated in the GLASS cohort. Correspondingly, class 2 and class 1 exhibited significant differences in mutation patterns, enriched pathways, programmed cell death (PCD), and the tumour immune microenvironment. Class 2 had more mutation signatures associated with defective DNA mismatch repair (P = 0.0021). Enriched pathways of differentially expressed genes in class 1 and class 2 (P-adjust

Abstract Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Abstract Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients’ prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors’ pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.

Abstract Background Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. Methods Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. Results Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. Conclusions In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.

Summary: Background: Establishing objective and quantitative neuroimaging biomarkers at individual level can assist in early and accurate diagnosis of major depressive disorder (MDD). However, most previous studies using machine learning to identify MDD were based on small sample size and did not account for the brain connectome that is associated with the pathophysiology of MDD. Here, we addressed these limitations by applying graph convolutional network (GCN) in a large multi-site MDD dataset. Methods: Resting-state functional MRI scans of 1586 participants (821 MDD vs. 765 controls) across 16 sites of Rest-meta-MDD consortium were collected. GCN model was trained with individual whole-brain functional network to identify MDD patients from controls, characterize the most salient regions contributing to classification, and explore the relationship between topological characteristics of salient regions and clinical measures. Findings: GCN achieved an accuracy of 81·5% (95%CI: 80·5–82·5%, AUC: 0·865), which was higher than other common machine learning classifiers. The most salient regions contributing to classification were primarily identified within the default mode, fronto-parietal, and cingulo-opercular networks. Nodal topologies of the left inferior parietal lobule and left dorsolateral prefrontal cortex were associated with depressive severity and illness duration, respectively. Interpretation: These findings based on a large, multi-site dataset support the feasibility and effectiveness of GCN in characterizing MDD, and also illustrate the potential utility of GCN for enhancing understanding of the neurobiology of MDD by detecting clinically-relevant disruption in functional network topology. Funding: This study was supported by the National Natural Science Foundation of China (Grant Nos. 81621003, 82027808, 81820108018).

To realize simultaneous adsorption of heavy metal and antibiotic pollutants by a BC-based recyclable material, Fe3O4 magnetic biochar (MBC) was prepared by co-precipitation method. Then different ratios of dodecyl dimethyl betaine (BS-12)-modified bentonite (BS-B) were loaded on the surfaces of biochar (BC) and MBC to prepare BS-B-loaded BC and MBC composites, called BS-B/BC and BS-B/MBC, respectively. The physicochemical and structural properties of the composites were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, thermogravimetric analysis, specific surface area (SBET) analysis, and vibrating sample magnetometry, and the adsorption efficiencies of BS-B/BC and BS-B/MBC to Cu2+ and tetracycline (TC) were studied. The following results were obtained. (1) Compared with BS-B/BC, BS-B/MBC had decreased pH and cation exchange capacity (CEC) and increased SBET. The pH, CEC, and SBET of BS-B/BC and BS-B/MBC decreased with the increase in the BS-12 proportion of BS-B. The surface of BS-B/MBC became rough after Fe3O4 loading. (2) The residual rate of BS-B/MBC was higher than that of BS-B/BC after high-temperature combustion, and the residual rate decreased with the increase in the BS-12 proportion of BS-B. The 2D infrared spectra showed that Fe3O4 and BS-12 were modified on the surface of BS-B/MBC. MBC and BS-B/MBC had splendid magnetism and could be separated by external magnetic field. (3) Compared with unmagnetized ones, the adsorption effects of Cu2+ and TC on different BS-B/MBCs improved, and the average adsorption rate reached the largest value of 91.92% and 97.76%, respectively. Cu2+ and TC adsorptions were spontaneous, endothermic, and entropy-increasing processes. The pH and SBET of the material had a great influence on Cu2+ and TC adsorptions, respectively, than CEC.

Pancreatic cancer: Exploring a pathway to drug resistance A cell membrane protein called PROM2 promotes the resistance of pancreatic cancer to the anti-cancer drug gemcitabine, suggesting PROM2 and the molecular signaling pathway it stimulates could be targeted by new treatments. Researchers in China led by Jian Sun at Sun Yat-Sen University, Guangzhou, investigated the role of PROM2 in cultured human pancreatic cancer cells and in a mouse model of pancreatic cancer. Production and activity of PROM2 were increased in cancer cells, leading to increased resistance to gemcitabine. The researchers found that PROM2’s promotion of gemcitabine resistance was linked to its ability to bind to another protein called Akt. This interaction stimulates the Akt signaling pathway, sustaining cancer cells. Combining gemcitabine therapy with an Akt pathway inhibitor restored cancer cell sensitivity to gemcitabine, revealing a potential approach to developing drugs to overcome gemcitabine resistance.

To explore the effects of modified pomace on copper migration via the soil on the banks of the rivers in northern Sichuan and Chongqing, fruit pomace (P) and ethylene diamine tetra-acetic acid (EDTA) modified P (EP) were evenly added (1% mass ratio) to the soil samples of Guanyuan, Nanbu, Jialing, and Hechuan from the Jialing River; Mianyang and Suining from the Fu River; and Guangan and Dazhou from the Qu River. The geochemical characteristics and migration rules of copper in different amended soils were simulated by column experiment. Results showed that the permeation time of copper in each soil column was categorized as EP-amended > P-amended > original soil, and the permeation time of amended soil samples at different locations was Jialing > Suining > Mianyang > Guangan > Dazhou > Nanbu > Guanyuan > Hechuan. Meanwhile, the average flow rate of copper in each soil column showed a reverse trend with the permeation time. Copper in exchangeable, carbonate, and iron–manganese oxide forms decreased with the increase of vertical depth in the soil column, among which the most evident decreases appeared in the carbonate-bonding form. The copper accumulation in different locations presented a trend of Jialing > Suining > Mianyang > Guangan > Dazhou > Nanbu > Guangyuan > Hechuan, and the copper content under the same soil showed EP-amended > P-amended > original soil. The copper proportion of the carbonate form was the highest in each soil sample, followed by the exchangeable form. The proportions of iron-manganese oxide and organic matter forms were relatively small. A significant correlation was observed between the cation exchange capacity and the copper content in exchangeable and carbonate forms. Moreover, total organic carbon and copper contents were negatively correlated.

Since hypobaric hypoxia significantly affects metabolic characteristics of intestinal flora, which plays an important role in the biotransformation of aspirin, high altitudes may influence the pharmacokinetics and therapeutic effects of aspirin in the intestines. In the present study, to test alterations of intestinal microbiota at high altitude comparing to that at low altitude, we analyzed rat feces from plain group and high-altitude group by 16S rRNA analysis. To detect concentrations of aspirin and salicylic acid, we established a reliable liquid chromatography tandem mass spectrometry method to measure aspirin and salicylic acid concentrations in fecal suspensions and plasma. Our study found that the plateau hypoxic environment caused a significant increase in Bacteroides in rat feces, while Corynebacterium, Prevotella, and Coprococcus were declined. In addition, compared with the plain group, the metabolic activity of fecal suspensions from the plateau group on aspirin was significantly reduced. More importantly, these changes in the intestinal microbiota led to increasing absorption of aspirin in the rats after rapidly ascent to the plateau, and a reduction in the pharmacodynamic index TXB2, which would possibly result in bleeding. In conclusion, our research provides new ideas for changes in plateau pharmacokinetics, and then guide the corresponding reduction in aspirin dose for the population quickly entering the plateau.

A floating power generation device is designed and fabricated to overcome the power supply limitations of wireless sensor networks for environmental monitoring. Once there is a temperature difference between the upper surface exposed to sunlight and the lower surface in the water, the device is capable of generating power while floating in the wetland environment. Fresnel lenses were applied to concentrate solar irradiation on a selective absorbing coat. Meanwhile two vertical axis rotors were used to cool the cold side of the thermoelectric power generator by catching the breeze. The effects of solar irradiation, temperature distribution, load resistance, wind speed, the maximum power and the electrical efficiency of the thermoelectric power generator were analyzed. When subjected to solar irradiation of 896.38 W/m2, the device generated a potential difference of 381.03 mV and a power output of 8.86 mW via thermoelectric generation. In addition, compared with the system without wind, the output power was increased by approximately 10.96% in our system. The low power wireless networks, used in wetland environments, could be operated by the thermoelectric power generated by the floating device. Besides, this system offers powering solution for self-power miniature devices that are applied in aqueous environment.

Sclerotinia stem rot (SSR) is a devastating fungal disease that causes severe yield losses of soybean worldwide. In the present study, a representative population of 185 soybean accessions was selected and utilized to identify the quantitative trait nucleotide (QTN) of partial resistance to soybean SSR via a genome-wide association study (GWAS). A total of 22,048 single-nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) > 5% and missing data < 3% were used to assess linkage disequilibrium (LD) levels. Association signals associated with SSR partial resistance were identified by two models, including compressed mixed linear model (CMLM) and multi-locus random-SNP-effect mixed linear model (mrMLM). Finally, seven QTNs with major effects (a known locus and six novel loci) via CMLM and nine novel QTNs with minor effects via mrMLM were detected in relation to partial resistance to SSR, respectively. One of all the novel loci (Gm05:14834789 on Chr.05), which was co-located by these two methods, might be a stable one that showed high significance in SSR partial resistance. Additionally, a total of 71 major and 85 minor candidate genes located in the 200-kb genomic region of each peak SNP detected by CMLM and mrMLM were found, respectively. By using a gene-based association, a total of six SNPs from three major effects genes and eight SNPs from four minor effects genes were identified. Of them, Glyma.18G012200 has been characterized as a significant element in controlling fungal disease in plants.

In eukaryotes, proteins encoded by the 14-3-3 genes are ubiquitously involved in the plant growth and development. The 14-3-3 gene family has been identified in several plants. In the present study, we identified 22 GmGF14 genes in the soybean genomic data. On the basis of the evolutionary analysis, they were clustered into ε and non-ε groups. The GmGF14s of two groups were highly conserved in motifs and gene structures. RNA-seq analysis suggested that GmGF14 genes were the major regulator of soybean morphogenesis. Moreover, the expression level of most GmGF14s changed obviously in multiple stress responses (drought, salt and cold), suggesting that they have the abilities of responding to multiple stresses. Taken together, this study shows that soybean 14-3-3s participate in plant growth and can response to various environmental stresses. These results provide important information for further understanding of the functions of 14-3-3 genes in soybean.

Abstract A high-performance and novel photocatalyst of BiVO4-reduced Graphene Oxide (BiVO4-rGO) nanocomposite was prepared by a facile hydrothermal method. The photocatalyst was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electronic microscopy, UV-Vis diffusion reflectance spectroscopy, photoluminescence spectroscopy and UV-Vis adsorption spectroscopy, respectively. The visible-light photocatalytic activity was evaluated by oxidation of methyl orange (MO) under simulated sunlight irradiation. The results show that the BiVO4-rGO nanocomposites exhibit enhanced photocatalytic performance for the degradation of MO with a maximum removal rate of 98.95% under visible light irradiation as compared with pure BiVO4 (57.55%) due to the increased light absorption intensity and the degradation of electron-hole pair recombination in BiVO4 with the introduction of the rGO.

Background VQ proteins, the plant-specific transcription factors, are involved in plant development and multiple stresses; however, only few articles systematic reported the VQ genes in soybean. Methods In total, we identified 75 GmVQ genes, which were classified into 7 groups (I-VII). Conserved domain analysis indicated that VQ gene family members all contain the VQ domains. VQ genes from the same evolutionary branches of soybean shared similar motifs and structures. Promoter analysis revealed that cis-elements related to stress responses, phytohormone responses and controlling physical as well as reproductive growth. Based on the RNA-seq and qRT-PCR analysis, GmVQ genes were showed expressing in nine tissues, suggesting their putative function in many aspects of plant growth and development as well as response to stress in Glycine max. Results This study aims to understand the roles of VQ genes in various development processes and their expression patterns in responses to stimuli. Our results provide basic information in identification and classification of GmVQ genes. Further experimental analysis will allows us to know the functions of GmVQs participation in plant growth and stress responses.

As a new strategy to power forest wireless sensors in remote areas, an environmental microenergy collection device has been improved, and field experiments were carried out under natural conditions for the first time. The thermoelectric power generation devices used a gravity-assisted heat pipe to transmit heat from shallow soil to ground level, and a thermoelectric generator (TEG) was employed to generate electric power from the temperature difference between soil and air. Over the 6-month experimental period at two natural sites, approximately 128.74 J of energy could be harvested in a single day, and 5 209.92 J of energy could be harvested in a generation cycle. The results showed the feasibility of using this green energy to power wireless sensors in remote forests or other environments, This work is relevant to the current acute energy shortages and environmental pollution problems.

Plant height (PH) is an important trait in soybean, as taller plants may have higher yields but may also be at risk for lodging. Many genes act jointly to influence PH throughout development. To map the quantitative trait loci (QTL) controlling PH, we used the unconditional variable method (UVM) and conditional variable method (CVM) to analyze PH data for a four-way recombinant inbred line (FW-RIL) population derived from the cross of (Kenfeng14 × Kenfeng15) × (Heinong48 × Kenfeng19). We identified 7, 8, 16, 19, 15, 27, 17, 27, 22, and 24 QTL associated with PH at 10 developmental stages, respectively. These QTL mapped to 95 genomic regions. Among these QTL, 9 were detected using UVM and CVM, and 89 and 66 were only detected by UVM or CVM, respectively. In total, 36 QTL controlling PH were detected at multiple developmental stages and these made unequal contributions to genetic variation throughout development. Among 19 novel regions discovered in our study, 7 could explain over 10% of the phenotypic variation and contained only one single QTL. The unconditional and conditional QTL detected here could be used in molecular design breeding across the whole developmental procedure.

RNA interference (RNAi) technology may be useful for developing new crop protection strategies against the soybean pod borer (SPB; Leguminivora glycinivorella), which is a critical soybean pest in northeastern Asia. Immune-related genes have been recently identified as potential RNAi targets for controlling insects. However, little is known about these genes or mechanisms underlying their expression in the SPB. In this study, we completed a transcriptome-wide analysis of SPB immune-related genes. We identified 41 genes associated with SPB microbial recognition proteins, immune-related effectors or signalling molecules in immune response pathways (e.g., Toll and immune deficiency pathways). Eleven of these genes were selected for a double-stranded RNA artificial feeding assay. The down-regulated expression levels of LgToll-5-1a and LgPGRP-LB2a resulted in relatively high larval mortality rates and abnormal development. Our data represent a comprehensive genetic resource for immune-related SPB genes, and may contribute to the elucidation of the mechanism regulating innate immunity in Lepidoptera species. Furthermore, two immune-related SPB genes were identified as potential RNAi targets, which may be used in the development of RNAi-mediated SPB control methods.

Pod number is an important factor that influences yield in soybean. Here, we used two associated recombinant inbred line (RIL) soybean populations, RIL3613 (containing 134 lines derived from Dongnong L13 × Heihe 36) and RIL6013 (composed of 156 individuals from Dongnong L13 × Henong 60), to identify quantitative trait loci (QTLs) regulating the vertical distribution and quantity of seeds and seed pods. The numbers of pods were quantified in the upper, middle, and lower sections of the plant, as well as in the plants as a whole, and QTLs regulating these spatial traits were mapped using an inclusive complete interval mapping method. A total of 21 and 26 QTLs controlling pod-number-related traits were detected in RIL3613 and RIL6013, respectively, which explained 1.25-11.6698% and 0.0001-7.91% of the phenotypic variation. A total of 34 QTLs were verified by comparison with previous research, were identified in both populations, or were found to regulate multiple traits, indicating their authenticity. These results enhance our understanding of the vertical distribution of pod-number-related traits and support molecular breeding for seed yield.

Plant regeneration can occur via in vitro tissue culture through somatic embryogenesis or de novo shoot organogenesis. Transformation of soybean (Glycine max) is difficult, hence optimization of the transformation system for soybean regeneration is required. This study investigated ENHANCER OF SHOOT REGENERATION 1 (GmESR1), a soybean transcription factor that targets regeneration-associated genes. Sequence analysis showed that GmESR1 contained a conserved 57 amino acid APETALA 2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) DNA-binding domain. The relative expression level of GmESR1 was highest in young embryos, flowers and stems in the soybean cultivar 'Dongnong 50'. To examine the function of GmESR1, transgenic Arabidopsis (Arabidopsis thaliana) and soybean plants overexpressing GmESR1 were generated. In Arabidopsis, overexpression of GmESR1 resulted in accelerated seed germination, and seedling shoot and root elongation. In soybean overexpression of GmESR1 also led to faster seed germination, and shoot and root elongation. GmESR1 specifically bound to the GCC-box. The results provide a foundation for the establishment of an efficient and stable transformation system for soybean.

In this paper, we present an automatic system for the analysis and labeling of structural scenes, floor plan drawings in Computer-aided Design (CAD) format. The proposed system applies a fusion strategy to detect and recognize various components of CAD floor plans, such as walls, doors, windows and other ambiguous assets. Technically, a general rule-based filter parsing method is fist adopted to extract effective information from the original floor plan. Then, an image-processing based recovery method is employed to correct information extracted in the first step. Our proposed method is fully automatic and real-time. Such analysis system provides high accuracy and is also evaluated on a public website that, on average, archives more than ten thousands effective uses per day and reaches a relatively high satisfaction rate.

The mini core collection (MCC) has been established by streamlining core collection (CC) chosen from China National Genebank including 23,587 soybean (Glycine max) accessions by morphological traits and simple sequence repeat (SSR) markers. Few studies have been focused on the maturity that has been considered as one of the most critical traits for the determination of the adaptation-growing region of the soybean. In the current study, two hundred and ninty-nine accessions of MCC planted for two years at four locations namely in Heihe, Harbin, Jining and Wuhan cities in China were used to assess the variation of maturity in MCC and identify the integrated effect of 4 E loci on flowering and maturity time in soybean. Forty-two North American varieties served as references of maturity groups (MG). Each accession in MCC was classified by comparing with the MG references in the days from VE (emergence) and physiological maturity (R7). The results showed that MCC covered a large range of MGs from MG000 to MGIX/X. Original locations and sowing types were revealed as the major affecting factors for maturity groups of the MCC accessions. The ratio of the reproductive period to the vegetative period (R/V) varied among MCC accessions. Genotyping of 4 maturity genes (i.e. E1, E2, E3 and E4) in 228 accessions indicated that recessive alleles e1, e2, e3 and e4 promoted earlier flowering and shortened the maturity time with different effects, while the dominate alleles were always detected in accessions with longer maturity. The allelic combinations determined the diversification of soybean maturity groups and adaptation to different regions. Our results indicated that the maturity of Chinese soybean MCC showed genetic diversities in phenotype and genotype, which provided information for further MG classification, geographic adaptation analysis of Chinese soybean cultivars, as well as developing new soybean varieties with adaptation to specific regions.

Soybean (Glycine max (L.) Merr.) isoflavone is important for human health and plant defense system. To identify novel quantitative trait loci (QTL) and epistatic QTL underlying isoflavone content in soybean, F5:6, F5:7 and F5:8 populations of 130 recombinant inbred (RI) lines, derived from the cross of soybean cultivar 'Zhong Dou 27' (high isoflavone) and 'Jiu Nong 20' (low isoflavone), were analyzed with 95 new SSR markers. A new linkage map including 194 SSR markers and covering 2,312 cM with mean distance of about 12 cM between markers was constructed. Thirty four QTL for both individual and total seed isoflavone contents of soybean were identified. Six, seven, ten and eleven QTL were associated with daidzein (DZ), glycitein (GC), genistein (GT) and total isoflavone (TI), respectively. Of them 23 QTL were newly identified. The qTIF_1 between Satt423 and Satt569 shared the same marker Satt569 with qDZF_2, qGTF_1 and qTIF_2. The qGTD2_1 between Satt186 and Satt226 was detected in four environments and explained 3.41%-10.98% of the phenotypic variation. The qGTA2_1, overlapped with qGCA2_1 and detected in four environments, was close to the previously identified major QTL for GT, which were responsible for large a effects. QTL (qDZF_2, qGTF_1 and qTIF_2) between Satt144-Satt569 were either clustered or pleiotropic. The qGCM_1, qGTM_1 and qTIM_1 between Satt540-Sat_244 explained 2.02%-9.12% of the phenotypic variation over six environments. Moreover, the qGCE_1 overlapped with qGTE_1 and qTIE_1, the qTIH_2 overlapped with qGTH_1, qGCI_1 overlapped with qDZI_1, qTIL_1 overlapped with qGTL_1, and qTIO_1 overlapped with qGTO_1. In this study, some of unstable QTL were detected in different environments, which were due to weak expression of QTL, QTL by environment interaction in the opposite direction to a effects, and/or epistasis. The markers identified in multi-environments in this study could be applied in the selection of soybean cultivars for higher isoflavone content and in the map-based gene cloning.

Pathogenesis-related proteins (PR proteins) play crucial roles in the plant defense system. A novel PRP gene was isolated from highly resistant soybean infected with Phytophthora sojae (P. sojae) and was named GmPRP (GenBank accession number: KM506762). The amino acid sequences of GmPRP showed identities of 74%, 73%, 72% and 69% with PRP proteins from Vitis vinifera, Populus trichocarpa, Citrus sinensis and Theobroma cacao, respectively. Quantitative real-time reverse transcription PCR (qRT-PCR) data showed that the expression of GmPRP was highest in roots, followed by the stems and leaves. GmPRP expression was upregulated in soybean leaves infected with P. sojae. Similarly, GmPRP expression also responded to defense/stress signaling molecules, including salicylic acid (SA), ethylene (ET), abscisic acid (ABA) and jasmonic acid (JA). GmPRP was localized in the cell plasma membrane and cytoplasm. Recombinant GmPRP protein exhibited ribonuclease activity and significant inhibition of hyphal growth of P. sojae 1 in vitro. Overexpression of the GmPRP gene in T2 transgenic tobacco and T2 soybean plants resulted in enhanced resistance to Phytophthora nicotianae (P. nicotianae) and P. sojae race 1, respectively. These results indicated that the GmPRP protein played an important role in the defense of soybean against P. sojae infection.

MicroRNAs (miRNAs) are short, non-coding single-strand RNA molecules that play important roles in plant growth, development and stress responses. Flowering time affects the seed yield and quality of soybean. However, the miRNAs involved in the regulation of flowering time in soybean have not been reported until recently. Here, high-throughput sequencing and qRT-PCR were used to identify miRNAs involved in soybean photoperiodic pathways. The first trifoliate leaves of soybean that receive the signal of light treatment were used to construct six libraries (0, 8, and 16 h under short-day (SD) treatment and 0, 8, and 16 h under long-day (LD) treatment). The libraries were sequenced using Illumina Solexa. A total of 318 known plant miRNAs belonging to 163 miRNA families and 81 novel predicted miRNAs were identified. Among these, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h, showed differences in abundance between LD and SD treatments. Furthermore, the results of GO and KEGG analyses indicated that most of the miRNA targets were transcription factors. Seven miRNAs at 0 h, 23 miRNAs (including four novel predicted miRNAs) at 8 h, 16 miRNAs (including one novel predicted miRNA) at 16 h and miRNA targets were selected for qRT-PCR analysis to assess the accuracy of the sequencing and target prediction. The results indicated that the expression patterns of the selected miRNAs and miRNA targets showed no differences between the qRT-PCR and sequencing results. In addition, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h responded to day length changes in soybean, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h. These results provided an important molecular basis to understand the regulation of flowering time through photoperiodic pathways in soybean.

The voltage between a standing tree and its surrounding soil is regarded as an innovative renewable energy source. This source is expected to provide a new power generation system for the low-power electrical equipment used in forestry. However, the voltage is weak, which has caused great difficulty in application. Consequently, the development of a method to increase the voltage is a key issue that must be addressed in this area of applied research. As the front-end component for energy harvesting, a metal electrode has a material effect on the level and stability of the voltage obtained. This study aimed to preliminarily ascertain the rules and mechanisms that underlie the effects of electrode material on voltage. Electrodes of different materials were used to measure the tree-source voltage, and the data were employed in a comparative analysis. The results indicate that the conductivity of the metal electrode significantly affects the contact resistance of the electrode-soil and electrode-trunk contact surfaces, thereby influencing the voltage level. The metal reactivity of the electrode has no significant effect on the voltage. However, passivation of the electrode materials markedly reduces the voltage. Suitable electrode materials are demonstrated and recommended.

To determine the prevalence and clinicopathological characteristics of BRAF V600E mutation and HER2 exon 20 insertions in Chinese lung adenocarcinoma (ADC) patients.Given the fact that the driver mutations are mutually exclusive in lung ADCs, 204 EGFR/KRAS wild-type cases were enrolled in this study. Direct Sanger sequencing was performed to examine BRAF V600E and HER2 exon 20 mutations. The association of BRAF and HER2 mutations with clinicopathological characteristics was statistically analyzed.Among the 204 lung ADCs tested, 11 cases (5.4%) carried HER2 exon 20 insertions and 4 cases (2.0%) had BRAF V600E mutation. HER2 mutation status was identified to be associated with a non-smoking history (p

We assessed the impact of species composition and stand structure on the spatial variation of forest carbon density using data collected from a 4-ha plot in a subtropical forest in southern China. We found that 1) forest biomass carbon density significantly differed among communities, reflecting a significant effect of community structure and species composition on carbon accumulation; 2) soil organic carbon density increased whereas stand biomass carbon density decreased across communities, indicating that different mechanisms might account for the accumulation of stand biomass carbon and soil organic carbon in the subtropical forest; and 3) a small number of tree individuals of the medium- and large-diameter class contributed predominantly to biomass carbon accumulation in the community, whereas a large number of seedlings and saplings were responsible for a small proportion of the total forest carbon stock. These findings demonstrate that both biomass carbon and soil carbon density in the subtropical forest are sensitive to species composition and community structure, and that heterogeneity in species composition and stand structure should be taken into account to ensure accurate forest carbon accounting.

In sporadic colorectal cancer (CRC), the BRAFV600E mutation is associated with deficient mismatch repair (MMR) status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR) CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR) CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+)/pMMR (34.0%), KRAS (+)/dMMR (2.9%), KRAS (-)/pMMR (58.5%) and KRAS (-)/dMMR (4.6%). A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%), proximal located (45.5%), a mucinous histology (38.4%), and to have increased lymph node metastasis (60.3%), compared with pMMR tumors without BRAFV600E and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01). To the contrary, compared with those with KRAS(-)/dMMR tumors, patients with KRAS(+)/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers.

Red-fleshed kiwifruit (Actinidia chinensis Planch. 'Hongyang') is a promising commercial cultivar due to its nutritious value and unique flesh color, derived from vitamin C and anthocyanins. In this study, we obtained transcriptome data of 'Hongyang' from seven developmental stages using Illumina sequencing. We mapped 39-54 million reads to the recently sequenced kiwifruit genome and other databases to define gene structure, to analyze alternative splicing, and to quantify gene transcript abundance at different developmental stages. The transcript profiles throughout red kiwifruit development were constructed and analyzed, with a focus on the biosynthesis and metabolism of compounds such as phytohormones, sugars, starch and L-ascorbic acid, which are indispensable for the development and formation of quality fruit. Candidate genes for these pathways were identified through MapMan and phylogenetic analysis. The transcript levels of genes involved in sucrose and starch metabolism were consistent with the change in soluble sugar and starch content throughout kiwifruit development. The metabolism of L-ascorbic acid was very active, primarily through the L-galactose pathway. The genes responsible for the accumulation of anthocyanin in red kiwifruit were identified, and their expression levels were investigated during kiwifruit development. This survey of gene expression during kiwifruit development paves the way for further investigation of the development of this uniquely colored and nutritious fruit and reveals which factors are needed for high quality fruit formation. This transcriptome data and its analysis will be useful for improving kiwifruit genome annotation, for basic fruit molecular biology research, and for kiwifruit breeding and improvement.

Photoperiod and sucrose levels play a key role in the control of flowering. GmRAV reflected a diurnal rhythm with the highest expression at 4 h after the beginning of a dark period in soybean leaves, and was highly up-regulated under short-day (SD) conditions, despite of not following a diurnal pattern under long-day (LD) conditions. GmRAV-i (GmRAV-inhibition) transgenic soybean exhibited early flowering phenotype. Two of the FT Arabidopsis homologs, GmFT2a and GmFT5a, were highly expressed in the leaves of soybeans with inhibition (-i) of GmRAV under SD conditions. Moreover, the transcript levels of the two FT homologs in GmRAV-i soybeans were more sensitive to SD conditions than LD conditions compared to the WT plant. GmRAV-i soybeans and Arabidopsis rav mutants showed more sensitive hypocotyl elongation responses when compared with wild-type seedlings, and GmRAV-ox overevpressed in tobacco revealed no sensitive changes in hypocotyl length. These indicated that GmRAV was a novel negative regulator of SD-mediated flowering and hypocotyl elongation. Although sucrose has been suggested to promote flowering induction in many plant species, high concentration of sucrose (4% [w/v]) applied into media defer flowering time in Arabidopsis wild-type and rav mutant. This delayed flowering stage might be caused by reduction of LEAFY expression. Furthermore, Arabidopsis rav mutants and GmRAV-i soybean plants were less sensitive to sucrose by the inhibition assays of hypocotyls and roots growth. In contrast, transgenic GmRAV overexpressing (-ox) tobacco plants displayed more sensitivity to sucrose. In conclusion, GmRAV was inferred to have a fundamental function in photoperiod, darkness, and sucrose signaling responses to regulate plant development and flowering induction.

Prophages are highly dynamic components in the bacterial genome and play an important role in intraspecies variations. There are at least two prophages in the chromosomes of Candidatus Liberibacter asiaticus' (Las) Floridian isolates. Las is both unculturable and the most prevalent species of Liberibacter pathogens that cause huanglongbing (HLB), a worldwide destructive disease of citrus. In this study, seven new prophage variants resulting from two hyper-variable regions were identified by screening clone libraries of infected citrus, periwinkle and psyllids. Among them, Types A and B share highly conserved sequences and localize within the two prophages, FP1 and FP2, respectively. Although Types B and C were abundant in all three libraries, Type A was much more abundant in the libraries from the Las-infected psyllids than from the Las-infected plants, and Type D was only identified in libraries from the infected host plants but not from the infected psyllids. Sequence analysis of these variants revealed that the variations may result from recombination and rearrangement events. Conventional PCR results using type-specific molecular markers indicated that A, B, C and D are the four most abundant types in Las-infected citrus and periwinkle. However, only three types, A, B and C are abundant in Las-infected psyllids. Typing results for Las-infected citrus field samples indicated that mixed populations of Las bacteria present in Floridian isolates, but only the Type D population was correlated with the blotchy mottle symptom. Extended cloning and sequencing of the Type D region revealed a third prophage/phage in the Las genome, which may derive from the recombination of FP1 and FP2. Dramatic variations in these prophage regions were also found among the global Las isolates. These results are the first to demonstrate the prophage/phage-mediated dynamics of Las populations in plant and insect hosts, and their correlation with insect transmission and disease development.

Large-scale genotyping plays an important role in genetic association studies. It has provided new opportunities for gene discovery, especially when combined with high-throughput sequencing technologies. Here, we report an efficient solution for large-scale genotyping. We call it specific-locus amplified fragment sequencing (SLAF-seq). SLAF-seq technology has several distinguishing characteristics: i) deep sequencing to ensure genotyping accuracy; ii) reduced representation strategy to reduce sequencing costs; iii) pre-designed reduced representation scheme to optimize marker efficiency; and iv) double barcode system for large populations. In this study, we tested the efficiency of SLAF-seq on rice and soybean data. Both sets of results showed strong consistency between predicted and practical SLAFs and considerable genotyping accuracy. We also report the highest density genetic map yet created for any organism without a reference genome sequence, common carp in this case, using SLAF-seq data. We detected 50,530 high-quality SLAFs with 13,291 SNPs genotyped in 211 individual carp. The genetic map contained 5,885 markers with 0.68 cM intervals on average. A comparative genomics study between common carp genetic map and zebrafish genome sequence map showed high-quality SLAF-seq genotyping results. SLAF-seq provides a high-resolution strategy for large-scale genotyping and can be generally applicable to various species and populations.

MicroRNAs (miRNAs) are a set of short (19∼24 nt) non-coding RNAs that play significant roles as posttranscriptional regulators in animals and plants. The ab initio prediction methods show excellent performance for discovering new pre-miRNAs. While most of these methods can distinguish real pre-miRNAs from pseudo pre-miRNAs, few can predict the positions of miRNAs. Among the existing methods that can also predict the miRNA positions, most of them are designed for mammalian miRNAs, including human and mouse. Minority of methods can predict the positions of plant miRNAs. Accurate prediction of the miRNA positions remains a challenge, especially for plant miRNAs. This motivates us to develop MaturePred, a machine learning method based on support vector machine, to predict the positions of plant miRNAs for the new plant pre-miRNA candidates.A miRNA:miRNA* duplex is regarded as a whole to capture the binding characteristics of miRNAs. We extract the position-specific features, the energy related features, the structure related features, and stability related features from real/pseudo miRNA:miRNA* duplexes. A set of informative features are selected to improve the prediction accuracy. Two-stage sample selection algorithm is proposed to combat the serious imbalance problem between real and pseudo miRNA:miRNA* duplexes. The prediction method, MaturePred, can accurately predict plant miRNAs and achieve higher prediction accuracy compared with the existing methods. Further, we trained a prediction model with animal data to predict animal miRNAs. The model also achieves higher prediction performance. It further confirms the efficiency of our miRNA prediction method.The superior performance of the proposed prediction model can be attributed to the extracted features of plant miRNAs and miRNA*s, the selected training dataset, and the carefully selected features. The web service of MaturePred, the training datasets, the testing datasets, and the selected features are freely available at http://nclab.hit.edu.cn/maturepred/.