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The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains.

Key Message: BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance in Arabidopsis roots. The formative divisions of cortex/endodermis initials (CEIs) and CEI daughter cells (CEIDs) in Arabidopsis roots are coordinately controlled by the longitudinal auxin gradient and the radial SHORT ROOT (SHR) abundance. However, the mechanism underlying this coordination remains poorly understood. In this study, we demonstrate that BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance. Mutations in BIG gene repressed cell cycle progression, delaying the formative divisions within the ground tissues and impairing the establishment of endodermal and cortical identities. In addition, we uncovered auxin's suppressive effect on BIG expression, triggering CYCLIND6;1 (CYCD6;1) activation in an SHR-dependent fashion. Moreover, the degradation of RETINOBLASTOMA-RELATED (RBR) is jointly regulated by BIG and CYCD6;1. The loss of BIG function led to RBR protein accumulation, detrimentally impacting the SHR/SCARECROW (SCR) protein complex and the CEI/CEID formative divisions. Collectively, these findings shed light on a fundamental mechanism wherein BIG intricately coordinates the interplay between SHR/SCR and auxin, steering ground tissue patterning within Arabidopsis root tissue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The increased soil salinity is becoming a major challenge to produce more crops and feed the growing population of the world. In this study, we demonstrated that overexpression of OsDIR55 gene enhances rice salt tolerance by altering the root diffusion barrier. OsDIR55 is broadly expressed in all examined tissues and organs with the maximum expression levels at lignified regions in rice roots. Salt stress upregulates the expression of OsDIR55 gene in an abscisic acid (ABA)-dependent manner. Loss-function and overexpression of OsDIR55 compromised and improved the development of CS and root diffusion barrier, manifested with the decreased and increased width of CS, respectively, and ultimately affected the permeability of the apoplastic diffusion barrier in roots. OsDIR55 deficiency resulted in Na + accumulation, ionic imbalance, and growth arrest, whereas overexpression of OsDIR55 enhances salinity tolerance and provides an overall benefit to plant growth and yield potential. Collectively, we propose that OsDIR55 is crucial for ions balance control and salt stress tolerance through regulating lignification-mediated root barrier modifications in rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

As a key regulator of plant photosynthesis, water use efficiency and immunity, stomata are specialized cellular structures that adopt defined shapes. However, our knowledge about the genetic players of stomatal pore formation and stomatal morphogenesis remains limited. Forward genetic screening, positional cloning, confocal and electron microscopy, physiological and pharmacological assays were employed for isolation and characterization of mutants and genes. We identified a mutant, dsm1, with impaired cytokinesis and deformed stomata. DSM1 is highly expressed in guard mother cells and guard cells, and encodes COBRA-LIKE 7 (COBL7), a plant-specific glycosylphosphatidylinositol (GPI)-anchored protein. COBRA-LIKE 7 and its closest homologue, COBL8, are first enriched on the forming cell plates during cytokinesis, and then their subcellular distribution and abundance change are correlated with the progressive stages of stomatal pore formation. Both COBL7 and COBL8 possess an ability to bind cellulose. Perturbing the expression of COBL7 and COBL8 leads to a decrease in cellulose content and inhibition of stomatal pore development. Moreover, we found that COBL7, COBL8 and CSLD5 have synergistic effects on stomatal development and plant growth. Our findings reveal that COBL7 plays a predominant and functionally redundant role with COBL8 in stomatal formation through regulating cellulose deposition and ventral wall modification in Arabidopsis., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Background: Short videos on social media are playing an increasingly important role in cancer health education today. It is important to explore how the actual communication effect of health videos and the knowledge absorption of users are influenced by different factors of the video creation process., Objective: The objective of our study is to access the factors influencing breast cancer health education through short videos on efficiency and quality., Methods: Three pairs of videos about breast health were created and participants completed questionnaires before and after watching the videos. A paired t -test was used to analyze within-group change scores. RM-ANOVA was used to assess the relationship between the pretest, posttest, and three variables., Results: Watching short videos can significantly increase viewers' knowledge of related health topics ( p  < 0.05). The viewers' concentration level while watching was significantly higher for the video with background music (BGM) than for the video without BGM ( p  = 0.006). The viewers' willingness to share was significantly higher for the video with a progress bar than for the video without a progress bar ( p  = 0.02). Using an interpreter wearing a doctor's uniform instead of casual wear and setting a progress bar can significantly improve the efficiency of knowledge absorption ( p  < 0.05)., Conclusion: A uniformed interpreter, BGM and a progress bar are factors influencing the efficiency of short health videos. They can be applied in video making to explore better ways of promoting cancer health education in the new mobile Internet environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Wu, Du, Zhuang, He, Ma, Zeng, Liang, Xu, Xie and Lin.)

Sangelose ® (SGL) is a novel hydroxypropyl methylcellulose (HPMC) derivative that has been hydrophobically modified. Due to its high viscosity, SGL has the potential as a gel-forming and release-rate-controlled material for application in swellable and floating gastroretentive drug delivery systems ( sf GRDDS). The aim of this study was to develop ciprofloxacin (CIP)-loaded sf GRDDS tablets comprised of SGL and HPMC in order to extend CIP exposure in the body and achieve optimal antibiotic treatment regimes. Results illustrated that SGL-HPMC-based sf GRDDS could swell to a diameter above 11 mm and showed a short floating lag time (<4 s) and long total floating time (>24 h) to prevent gastric emptying. In dissolution studies, CIP-loaded SGL-HPMC sf GRDDS demonstrated a specific biphasic release effect. Among the formulations, the SGL/type-K HPMC 15,000 cps (HPMC 15K) (50:50) group exhibited typical biphasic release profiles, with F4-CIP and F10-CIP individually releasing 72.36% and 64.14% CIP within 2 h dissolution, and sustaining release to 12 h. In pharmacokinetic studies, the SGL-HPMC-based sf GRDDS demonstrated higher C max (1.56-1.73 fold) and shorter T max (0.67 fold) than HPMC-based sf GRDDS. Furthermore, SGL 90L in GRDDS indicated an excellent biphasic release effect and a maximum elevation of relative bioavailability (3.87 fold). This study successfully combined SGL and HPMC to manufacture sf GRDDS that retain CIP in the stomach for an optimal duration while improving its pharmacokinetic characteristics. It was concluded that the SGL-HPMC-based sf GRDDS is a promising biphasic antibiotic delivery system that can both rapidly achieve the therapeutic antibiotic concentration and maintain the plasma antibiotic concentration for an extended period to maximize antibiotic exposure in the body.

A palladium-catalyzed intramolecular Heck/aminocarbonylation of alkene-tethered iodobenzenes with nitro compounds has been developed for the synthesis of carbamoyl-substituted benzoheterocycles. Using Mo(CO) 6 as a solid CO source, no external reductant or additives were needed in this procedure. Both nitroarenes and nitroalkanes were well tolerated. A range of carbamoyl-substituted dihydrobenzofurans and indolines were prepared in moderate to high yields.

Dirigent (DIR) members have been shown to play essential roles in plant growth, development and adaptation to environmental changes. However, to date, there has been no systematic analysis of the DIR members in the genus Oryza . Here, 420 genes were identified from nine rice species to have the conserved DIR domain. Importantly, the cultivated rice species Oryza sativa has more DIR family members than the wild rice species. DIR proteins in rice could be classified into six subfamilies based on phylogeny analysis. Gene duplication event analysis suggests that whole genome/segmental duplication and tandem duplication are the primary drivers for DIR genes' evolution in Oryza , while tandem duplication is the main mechanism of gene family expansion in the DIR-b/d and DIR-c subfamilies. Analysis of the RNA sequencing data indicates that OsjDIR genes respond to a wide range of environmental factors, and most OsjDIR genes have a high expression level in roots. Qualitative reverse transcription PCR assays confirmed the responsiveness of OsjDIR genes to the undersupply of mineral elements, the excess of heavy metals and the infection of Rhizoctonia solani . Furthermore, there exist extensive interactions between DIR family members. Taken together, our results shed light on and provide a research foundation for the further exploration of DIR genes in rice.

Plant growth and crop yield are essentially determined by photosynthesis when considering carbon dioxide (CO 2 ) availability. CO 2 diffusion inside a leaf is one of the factors that dictate the CO 2 concentrations in chloroplasts. Carbonic anhydrases (CAs) are zinc-containing enzymes that interconvert CO 2 and bicarbonate ions (HCO 3 - ), which, consequently, affect CO 2 diffusion and thus play a fundamental role in all photosynthetic organisms. Recently, the great progress in the research in this field has immensely contributed to our understanding of the function of the β-type CAs; however, the analysis of α-type CAs in plants is still in its infancy. In this study, we identified and characterized the OsαCA1 gene in rice via the analysis of OsαCAs expression in flag leaves and the subcellular localization of its encoding protein. OsαCA1 encodes an α-type CA, whose protein is located in chloroplasts with a high abundance in photosynthetic tissues, including flag leaves, mature leaves, and panicles. OsαCA1 deficiency caused a significant reduction in assimilation rate, biomass accumulation, and grain yield. The growth and photosynthetic defects of the OsαCA1 mutant were attributable to the restricted CO 2 supply at the chloroplast carboxylation sites, which could be partially rescued by the application of an elevated concentration of CO 2 but not that of HCO 3 - . Furthermore, we have provided evidence that OsαCA1 positively regulates water use efficiency (WUE) in rice. In summary, our results reveal that the function of OsαCA1 is integral to rice photosynthesis and yield potential, underscoring the importance of α-type CAs in determining plant physiology and crop yield and providing genetic resources and new ideas for breeding high-yielding rice varieties.

Background: S-Detect is a computer-assisted, artificial intelligence-based system of image analysis that has been integrated into the software of ultrasound (US) equipment and has the capacity to independently differentiate between benign and malignant focal breast lesions. Since the revision and upgrade in both the breast imaging-reporting and data system (BI-RADS) US lexicon and the S-Detect software in 2013, evidence that supports improved accuracy and specificity of radiologists' assessment of breast lesions has accumulated. However, such assessment using S-Detect technology to distinguish malignant from breast lesions with a diameter no greater than 2 cm requires further investigation., Methods: The US images of focal breast lesions from 295 patients in our hospital from January 2019 to June 2022 were collected. The BI-RADS data were evaluated by the embedded program and as manually modified prior to the determination of a pathological diagnosis. The receiver operator characteristic (ROC) curves were constructed to compare the diagnostic accuracy between the assessments of the conventional US images, the S-Detect classification, and the combination of the two., Results: There were 326 lesions identified in 295 patients, of which pathological confirmation demonstrated that 239 were benign and 87 were malignant. The sensitivity, specificity, and accuracy of the conventional imaging group were 75.86%, 93.31%, and 88.65%. The sensitivity, specificity, and accuracy of the S-Detect classification group were 87.36%, 88.28%, and 88.04%, respectively. The assessment of the amended combination of S-Detect with US image analysis (Co-Detect group) was improved with a sensitivity, specificity, and accuracy of 90.80%, 94.56%, and 93.56%, respectively. The diagnostic accuracy of the conventional US group, the S-Detect group, and the Co-Detect group using area under curves was 0.85, 0.88 and 0.93, respectively. The Co-Detect group had a better diagnostic efficiency compared with the conventional US group ( Z = 3.882, p = 0.0001) and the S-Detect group ( Z = 3.861, p = 0.0001). There was no significant difference in distinguishing benign from malignant small breast lesions when comparing conventional US and S-Detect techniques., Conclusions: The addition of S-Detect technology to conventional US imaging provided a novel and feasible method to differentiate benign from malignant small breast nodules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Chen, Wang, Li, Liang and Wang.)

Lipid droplets (LDs) are evolutionarily conserved organelles that serve as hubs of cellular lipid and energy metabolism in virtually all organisms. Mobilization of LDs is important in light-induced stomatal opening. However, whether and how LDs are involved in stomatal development remains unknown. We show here that Arabidopsis thaliana LIPID DROPLETS AND STOMATA 1 (LDS1)/RABC1 (At1g43890) encodes a member of the Rab GTPase family that is involved in regulating LD dynamics and stomatal morphogenesis. The expression of RABC1 is coordinated with the different phases of stomatal development. RABC1 targets to the surface of LDs in response to oleic acid application in a RABC1GEF1-dependent manner. RABC1 physically interacts with SEIPIN2/3, two orthologues of mammalian seipin, which function in the formation of LDs. Disruption of RABC1, RABC1GEF1, or SEIPIN2/3 resulted in aberrantly large LDs, severe defects in guard cell vacuole morphology, and stomatal function. In conclusion, these findings reveal an aspect of LD function and uncover a role for lipid metabolism in stomatal development in plants., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Growth at increased concentrations of CO 2 induces a reduction in seed zinc (Zn) and iron (Fe). Using Arabidopsis thaliana, we investigated whether this could be mitigated by reducing the elevated CO 2 -induced decrease in transpiration. We used an infrared imaging-based screen to isolate mutants in At1g08080 that encodes ALPHA CARBONIC ANHYDRASE 7 (ACA7). aca7 mutant alleles display wild-type (WT) responses to abscisic acid (ABA) and light but are compromised in their response to elevated CO 2 . ACA7 is expressed in guard cells. When aca7 mutants are grown at 1000 ppm CO 2 they exhibit higher transpiration and higher seed Fe and Zn content than WT grown under the same conditions. Our data show that by increasing transpiration it is possible to partially mitigate the reduction in seed Fe and Zn content when Arabidopsis is grown at elevated CO 2 ., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Glycogen synthase kinase 3 (GSK3) proteins play key roles in brassinosteroid (BR) signaling during plant growth and development by phosphorylating various substrates. However, how GSK3 protein stability and activity are themselves modulated is not well understood. Here, we demonstrate in vitro and in vivo that C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (OsCPL3), a member of the RNA Pol II CTD phosphatase-like family, physically interacts with OsGSK2 in rice (Oryza sativa). OsCPL3 expression was widely detected in various tissues and organs including roots, leaves and lamina joints, and was induced by exogenous BR treatment. OsCPL3 localized to the nucleus, where it dephosphorylated OsGSK2 at the Ser-222 and Thr-284 residues to modulate its protein turnover and kinase activity, in turn affecting the degradation of BRASSINAZOLE-RESISTANT 1 (BZR1) and BR signaling. Loss of OsCPL3 function resulted in higher OsGSK2 abundance and lower OsBZR1 levels, leading to decreased BR responsiveness and alterations in plant morphology including semi-dwarfism, leaf erectness and grain size, which are of fundamental importance to crop productivity. These results reveal a previously unrecognized role for OsCPL3 and add another layer of complexity to the tightly controlled BR signaling pathway in plants., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

BIG, a regulator of polar auxin transport, is necessary to regulate the growth and development of Arabidopsis. Although mutations in the BIG gene cause severe root developmental defects, the exact mechanism remains unclear. Here, we report that disruption of the BIG gene resulted in decreased quiescent center (QC) activity and columella cell numbers, which was accompanied by the downregulation of WUSCHEL-RELATED HOMEOBOX5 ( WOX5 ) gene expression. BIG affected auxin distribution by regulating the expression of PIN-FORMED proteins (PINs), but the root morphological defects of big mutants could not be rescued solely by increasing auxin transport. Although the loss of BIG gene function resulted in decreased expression of the PLT1 and PLT2 genes, genetic interaction assays indicate that this is not the main reason for the root morphological defects of big mutants. Furthermore, genetic interaction assays suggest that BIG affects the stem cell niche (SCN) activity through the SCRSCARECROW (SCR)/SHORT ROOT (SHR) pathway and BIG disruption reduces the expression of SCR and SHR genes. In conclusion, our findings reveal that the BIG gene maintains root meristem activity and SCN integrity mainly through the SCR/SHR pathway.

Background: In our previous research, we developed a 32-gene risk index model that may be utilized as a robust prognostic method for predicting prostate cancer (PCa) recurrence after surgery. Among the 32 genes, the Fifth Ewing Variant ( FEV ) gene was one of the top downregulated genes in relapsed PCa. However, current understanding of the FEV gene and its involvement in PCa is limited., Methods: FEV mRNA expression was analyzed and correlated to clinical outcomes in PCa patients who underwent prostatectomy at the Massachusetts General Hospital. Specimens from tissue microarray (TMA) including 102 prostate cancer patients were analysis for the expression of FEV. Meanwhile, FEV expression profiles were also assessed in PCa cell lines and in BPH-1 prostate epithelial cells using western blotting and quantitative reverse transcription-PCR (qRT-PCR). Furthermore, we transfected LNCaP and PC-3 cells with either an empty vector or full-length FEV gene and performed in vitro cell functional assays. The part FEV plays in tumor xenograft growth was also assessed in vivo., Results: Of the 191 patients included in this study base on the DASL dataset, 77 (40.3%) and 24 (13.6%), respectively, developed prostate-specific antigen (PSA) relapse and metastasis postradical prostatectomy. Significant FEV downregulation was observed in PCa patients showing PSA failure and metastasis. The protein expression of FEV was significantly negatively correlated with the Gleason score and pathological stage in prostate cancer tissues. Similarly, FEV expression significantly decreased in all PCa cell lines relative to BPH-1 (all P < 0.05). Functional assays revealed that FEV expression markedly inhibited PCa cell growth, migration, and invasion, which in turn significantly repressed the growth of tumor xenografts in vivo., Conclusion: The results of this study suggest an association between downregulated FEV expression and PSA relapse in PCa patients. In addition, FEV may act as a tumor suppressor in PCa., Competing Interests: The authors declare that they do not have any potential conflicts of interest to disclose., (Copyright © 2022 Yu-Xiang Liang et al.)

Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population., Methods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker., Results: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066])., Conclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Wang, Chen, Shi, Zhang, Lin, Liang, Xiao, Wu, Yuan and Qiu.)

Root hairs are cylindrical extensions of root epidermal cells that are important for the acquisition of water and minerals, interactions between plant and microbes. The deposition of cell wall materials in the tip enables root hairs to maintain elongation constantly. To date, our knowledge of the regulators that connect the architecture of cell wall and the root hair development remains very limited. Here, we demonstrated that COBL9 and COBL7, two genes of COBRA-Like family in Arabidopsis as well as their counterparts in rice, OsBC1L1 and OsBC1L8, regulate root hair growth. Single mutant cobl9, double mutants cobl7 cobl9 and double mutants osbc1l1 osbc1l8 all displayed prematurely terminated root hair elongation, though at varying levels. COBL7-YFP and COBL9-YFP accumulate prominently in the growing tips of newly emerged root hairs. Furthermore, cobl9, cobl7 cobl9 and osbc1l1 osbc1l8 mutants were defective in the enrichment of cellulose in the tips of the growing root hairs. We also discovered that overexpression of COBL9 could promote root hair elongation and salinity tolerance. Taken together, these results provide compelling evidence that the polarized COBL7 and COBL9 in the tip of the emerging root hairs have conserved roles in regulating root hair development and stress adaptation in dicots and monocots., Competing Interests: Declaration of competing interest No potential conflict of interest is disclosed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stomata that are bordered by pairs of guard cells are specialized for regulating gas exchange and transpiration in plants. The stomatal morphology of grass is unique, characterized by two dumbbell-shaped guard cells flanked by two lateral subsidiary cells. This morphology and developmental pattern enable grass stomata to respond to environmental signals efficiently. In this study, we demonstrated that knockout either OsBC1L1 or OsBC1L8, two close homologs of OsBC1L family causes no discernible defects in rice stomatal development, however, the double knockout mutant osbc1l1 osbc1l8 exhibits excess stomatal production and stomatal clustering. OsBC1L1 overexpression also causes abnormal stomatal patterning in rice. Moreover, osbc1l1 osbc1l8 has many defective stomata complexes with only one subsidiary cell. The expression of OsSPCH2 and OsFAMA, two genes key to stomatal development is both down-regulated in osbc1l1 osbc1l8. In contrast, overexpressing OsBC1L1 suppresses only the expression of OsSPCH2. Both OsBC1L1 and OsBC1L8 could be detected to be localized at the cell plate and plasma membrane during cell division of guard mother cells and subsidiary mother cells. Taken together, these results suggest that OsBC1L1 and OsBC1L8 play essential roles in the development of rice stomatal complex likely through their involvement in cell reproduction., Competing Interests: Declaration of competing interest No potential conflict of interest is disclosed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune-related gene (IRG)-based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF-related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow-up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG-based signature from the specific module. Risk plot analyses, Kaplan-Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell's concordance index were used to assess the prognostic value and predictive accuracy of the IRG-based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG-based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG-based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low-risk and high-risk groups in PRAD. We identified a novel IRG-based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Deng, Chen, Qiu, Xiao, Qi, Xie, Wang, Jia, Zeng and Lin.)

A visible-light-induced carbonylation of indoles with phenols for the synthesis of indole-3-carboxylates has been developed. The reaction proceeded via a radical carbonylation process in which elementary I 2 was used as an effective photosensitive initiator and, thus, avoided the use of transition metal catalysts. A series of different aryl indole-3-carboxylates were prepared in moderate to good yields. The broad applicability of this methodology was further highlighted by the late-stage functionalization of several phenol-containing natural products and pharmaceuticals.

Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

In plants, stomata control water loss and CO 2 uptake. The aperture and density of stomatal pores, and hence the exchange of gases between the plant and the atmosphere, are controlled by internal factors such as the plant hormone abscisic acid (ABA) and external signals including light and CO 2 . In this study, we examine the importance of ABA catabolism in the stomatal responses to CO 2 and light. By using the ABA 8'-hydroxylase-deficient Arabidopsis thaliana double mutant cyp707a1 cyp707a3 , which is unable to break down and instead accumulates high levels of ABA, we reveal the importance of the control of ABA concentration in mediating stomatal responses to CO 2 and light. Intriguingly, our experiments suggest that endogenously produced ABA is unable to close stomata in the absence of CO 2 . Furthermore, we show that when plants are grown in short day conditions ABA breakdown is required for the modulation of both elevated [CO 2 ]-induced stomatal closure and elevated [CO 2 ]-induced reductions in leaf stomatal density. ABA catabolism is also required for the stomatal density response to light intensity, and for the full range of light-induced stomatal opening, suggesting that ABA catabolism is critical for the integration of stomatal responses to a range of environmental stimuli., Competing Interests: The authors declare no competing financial interests., (© 2021 The Author(s).)

Amide synthesis is one of the most important transformations in organic chemistry due to their ubiquitous presence in our daily life. In this communication, a palladium catalyzed cascade azidation/carbonylation of aryl halides for the synthesis of amides was developed. Both iodo- and bromobenzene derivatives were transformed to the corresponding amides using PdCl 2 /xantphos as the catalyst system and sodium azide as the nitrogen-source. The reaction proceeds via a cascade azidation/carbonylation process. A range of alkyl and halogen substituted amides were prepared in moderate to good yields., (© 2021 Wiley-VCH GmbH.)

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.

Plants have evolved an innate immune system to protect themselves from pathogen invasion with the help of intracellular nucleotide-binding leucine-rich repeat (NLR) receptors, though the mechanisms remain largely undefined. RIN13 (RPM1-interacting protein 13) was previously reported to enhance disease resistance, and suppress RPM1 (a CNL-type NLR)-mediated hypersensitive response in Arabidopsis via an as yet unknown mechanism. Here, we show that RIN13 is a nuclear-localized protein, and functions therein. Overexpression of RIN13 leads to autoimmunity with high accumulation of salicylic acid (SA), constitutive expression of pathogenesis-related genes, enhanced resistance to a virulent pathogen, and dwarfism. In addition, genetic and transcriptome analyses show that SA-dependent and SA-independent pathways are both required for RIN13-mediated disease resistance, with the EDS1/PAD4 complex as an integration point. RIN13-induced dwarfism was rescued completely by either the pad4-1 or the eds1-2 mutant but partially by snc1-r1, a mutant of the TNL gene SNC1, suggesting the involvement of EDS1/PAD4 and SNC1 in RIN13 functioning. Furthermore, transient expression assays indicated that RIN13 promotes the nuclear accumulation of PAD4. Collectively, our study uncovered a signaling pathway whereby SNC1 and EDS1/PAD4 act together to modulate RIN13-triggered plant defense responses., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients., Methods: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism., Results: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy., Conclusion: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC., (© 2020 UICC.)

Elevated CO 2 (eCO 2 ) often reduces leaf stomatal aperture and density thus impacts plant physiology and productivity. We have previously demonstrated that the Arabidopsis BIG protein distinguishes between the processes of eCO 2 -induced stomatal closure and eCO 2 -inhibited stomatal opening. However, the mechanistic basis of this action is not fully understood. Here we show that eCO 2 -elicited reactive oxygen species (ROS) production in big mutants was compromised in stomatal closure induction but not in stomatal opening inhibition. Pharmacological and genetic studies show that ROS generated by both NADPH oxidases and cell wall peroxidases contribute to eCO 2 -induced stomatal closure, whereas inhibition of light-induced stomatal opening by eCO 2 may rely on the ROS derived from NADPH oxidases but not from cell wall peroxidases. As with JA and ABA, SA is required for eCO 2 -induced ROS generation and stomatal closure. In contrast, none of these three signals has a significant role in eCO 2 -inhibited stomatal opening, unveiling the distinct roles of plant hormonal signaling pathways in the induction of stomatal closure and the inhibition of stomatal opening by eCO 2 . In conclusion, this study adds SA to a list of plant hormones that together with ROS from distinct sources distinguish two branches of eCO 2 -mediated stomatal movements., (Copyright © 2020 He, Zhang, Kim, Sun, Liu, Liu, Hetherington and Liang.)

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 ( w / w / w ) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that C max /dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.

The complete mitochondrial genome (mitogenome) of the leopard cat Prionailurus bengalensis in China was sequenced using the shotgun genome-skimming method. The mitogenome of P. bengalensis is totally 17,006 bp in length with a higher A + T content of 60.4% than that of G + C and consists of 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region. All the PCGs initiate with a typical ATN codon and terminate with a TAA codon except for the four PCGs ( COX1 , ND2 , ND3 , and ND4 ) terminating with a single T-and one gene CYT B with AGA as stop codon. Most of the tRNA genes have a clover-leaf secondary structure except for tRNAS (AGN), which loses a dihydrouridine (DHU) arm. The ML phylogenetic tree showed that P. viverrinus nested in the group of P. bengalensis individuals, which is close to the clade clustered by the two genera Otocolobus and Felis ., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis., Methods: The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated., Results: Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011)., Conclusions: Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.

We sequenced the complete mitochondrial genome (mitogenome) of Siberian Roe Deer, Capreolus pygargus , in China by the shotgun genome-skimming methods. The mitogenome of C. pygargus is totally 16,353 bp in length and contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a control region. The sequence has a higher A + T content of 63.4% than G + C 36.6% and with a base composition of 33.4% A, 23.2% C, 13.4% G, and 30.0% T. All of the 13 PCGs initiate a typical ATN codon except Nd4L with GTG. Six PCGs terminate with a TAA codon, while Cyt b, Atp8, and Nd1 terminate with AGA, TAG, and TA-, respectively. Whereas, Cox3 , Nd2 , Nd3 , and Nd4 terminate with a single T-. The phylogenetic trees of the subfamily Capreolinae with 13 PCGs indicated that Capreolus species were well-supported as a monophyletic group, which is sister to the clade of Hydropotes with well-support., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

We sequenced the complete mitochondrial genome of the Chinese Rhus gall aphid Meitanaphis microgallis (Hemiptera: Aphididae: Eriosomatinae: Fordini) by the genome skimming method on an Illunima platform. The assembled mitogenome is 16,191 bp in length with a very high A + T content of 84.3%. This genome consists of 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control region. All the protein-coding genes have a typical ATN initiation codon and TAA termination codon except COX1 and ND4 with a single T as stop codon. The tRNAs ranged in size from 59 to 77 bp and formed a clover-leaf secondary structure except tRNA-Ser (AGN). We constructed the phylogenetic relationship of Fordini aphids including all the Rhus gall aphids, and the ML tree showed that M. microgallis grouped with M. elongallis as its sister group., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD-L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD-L1 was frequently observed in the nerve branches in the tumor-associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3-, CD3- and CD8-positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD-L1 + tumor-associated nerves (TANs) was inversely correlated with that of CD8 + TALs. Higher density of PD-L1 + TANs was significantly associated with biochemical recurrence (BCR) in Kaplan-Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD-L1 + TANs was independently prognostic of BCR. In conclusion, PD-L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8 + TALs. Neuro-immunological interaction may be a contribution to immune-suppressive microenvironment. Combinatorial treatment regimen designs to neural PD-L1 and TALs should be warranted in future clinical application of anti-PD-L1/PD-1 immunotherapy in prostate cancer., (© 2018 UICC.)

Biochar, pyrolyzed from agricultural biomass wastes, has been widely used as an improver in wastewater treatment to regulate the oxygen distributions and microbial communities because of its extended surface area and porous structure. In addition, biochar has been shown to play a role in enhancing the porosity, adsorbing ammonium (NH 4 + -N), and reducing nitrous oxide (N 2 O) emissions. In this paper, five groups of constructed microcosm wetlands (CW) were built in a greenhouse with different biochar doses of 40%, 30%, 20%, 10%, and 0% (named as BW-40, BW-30, BW-20, BW-10, and CW-K, respectively) to investigate the influences of biochar on pollutant removal efficiencies and N 2 O emissions. The results showed that the concentration of effluent dissolved oxygen (DO) was less than 0.5 mg·L -1 , and the pH was stable at around 7.2 in every CW. Additionally, the effluent oxidation-reduction potential (ORP) was found to have moderately increased with the increases in the quantity of biochar, and the conductivity (Cond) test results showed the opposite trend. However, the effects of biochar on DO, pH, ORP, and Cond were not significant ( P >0.05). The chemical oxygen demand (COD) removal rates were up to 90% in all CWs. On the other hand, significantly higher removal efficiencies for NH 4 + -N and total nitrogen (TN) were found in CWs filled with biochar ( P <0.05). The average NH 4 + -N removal rates were (57.96±10.63)%, (51.12±11.74)%, (48.55±8.75)%, (43.95±9.74)%, and (34.76±14.16)% in BW-40, BW-30, BW-20, BW-10, and CW-K, respectively, while the total nitrogen (TN) average removal rates were (80.21±10.63)%, (78.48±5.73)%, (76.80±4.20)%, (75.88±5.85)%, and (70.92±5.68)%, respectively. Nitrate (NO 3 - -N) was not detected in the CWs for there were sufficient carbon sources and suitable denitrification environments. Moreover, the average fluxes of N 2 O ranged from 13.53 mg·(m 2 ·d) -1 to 45.30 mg·(m 2 ·d) -1 in the experimental systems. Compared with the control, the reduction rates of N 2 O in the BW-40, BW30, BW20, and BW10 were 70.13%, 68.26%, 50.83%, and 37.90%, respectively, and the ratios of N 2 O emissions to the removed nitrogen in CWs with biochar were significantly lower than those in the CW without biochar. Positive correlations were observed between the N 2 O fluxes and nitrite (NO 2 - -N) concentrations, and the lower N 2 O emissions could be attributed to the higher oxygen transfer and lower NO 2 - -N accumulation rates in response to the biochar addition. These results demonstrate that biochar could be used as an amendment to strengthen the nitrogen removal and reduce the N 2 O emissions in CWs.

Plants have evolved an array of responses that provide them with protection from attack by microorganisms and other predators. Many of these mechanisms depend upon interactions between the plant hormones jasmonate (JA) and ethylene (ET). However, the molecular basis of these interactions is insufficiently understood. Gene expression and physiological assays with mutants were performed to investigate the role of Arabidopsis BIG gene in stress responses. BIG transcription is downregulated by methyl JA (MeJA), necrotrophic infection or mechanical injury. BIG deficiency promotes JA-dependent gene induction, increases JA production but restricts the accumulation of both ET and salicylic acid. JA-induced anthocyanin accumulation and chlorophyll degradation are enhanced and stomatal immunity is impaired by BIG disruption. Bacteria- and lipopolysaccaride (LPS)-induced stomatal closure is reduced in BIG gene mutants, which are hyper-susceptible to microbial pathogens with different lifestyles, but these mutants are less attractive to phytophagous insects. Our results indicate that BIG negatively and positively regulate the MYC2 and ERF1 arms of the JA signalling pathway. BIG warrants recognition as a new and distinct regulator that regulates JA responses, the synergistic interactions of JA and ET, and other hormonal interactions that reconcile the growth and defense dilemma in Arabidopsis., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)

In the subsurface flow of a constructed wetland (CW) used for treating wastewater, low oxygen diffusion results in long-term anoxic or anaerobic surroundings, which cannot meet the needs of plant respiration and poses a threat to the survival of macrophytes. Although sweet sedge ( Acorus calamus L.) has a significant ability to resist hypoxia, membrane lipid oxidation would still occur in the plant due to the long-term hypoxia in the CW. According to reports in the existing literature, activation of the antioxidative response system could be promoted by adding biochar, thereby significantly decreasing the malonic dialdehyde in the plants. However, the specific reasons why biochar alleviates the stress from anoxia are still not clear. Thus, the responses of macrophyte roots to biochar application were studied in five different CWs built in a greenhouse, using plant ecology analyses combined with root aerenchyma, root porosity, and radial oxygen loss (ROL). The results showed that adding biochar to CW was beneficial for sweet sedge to form root aerenchyma and to increase root porosity. Moreover, there was a significant positive correlation between root porosity and the amount of biochar applied. Photosynthetic metabolism could be indirectly promoted by biochar application by increasing oxygen partial pressure in the blades, helping to transport O 2 to underground parts through aerenchyma, and spreading O 2 to the rhizosphere in the form of ROL. The reduction environment could be improved by applying biochar in CWs, which was also beneficial for ROL. Compared with other light conditions, 3000 μmol·(m 2 ·s) -1 was more suitable for the growth of A. calamus in CWs with biochar, where the ability of the plants to secrete oxygen would be stimulated and enhanced. However, the effect of the biochar application ratio on ROL was not significant.

Stomata are microscopic pores on the surface of leaves through which water as vapor passes to the atmosphere and CO 2 uptake for the photosynthesis. The signaling peptides of the epidermal patterning factor (EPF) family regulate stomatal development and density in Arabidopsis. Several putative homologs of EPF/EPFL exist in rice genome. To understand their possible involvement in stomatal formation, in this study we generated a series of transgenic lines including reporter promoter fusions, down-regulation and overexpression and demonstrated drastic differences in stomatal densities between different genotypes, as elevated expression of OsEPF1 or OsEPF2 greatly reduced stomatal density in rice, whereas ectopic overexpression of either OsEPF1 or OsEPF2 significantly decreased the high stomatal frequency of both mutant lines of epf2 and epf1epf2 Arabidopsis. Conversely, knocking down OsEPFL9 transcription conferred transgenic plants with fewer stomata than WT in rice, whereas overexpressing rice OsEPFL9 gene could cause excessive production of stomata in Arabidopsis. In conclusion, homologs of EPF/EPFL regulate stomatal development in a generally highly conserved way yet there exist function distinctions between dicot and monocot plants., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Mutations in BIG gene not only produce pleiotropic phenotypes of plant development but also impair plant adaptive responses under various stresses. However, the role of BIG gene in sugar signaling is not known. In this study, we first found that BIG deficiency significantly sensitized the sugar-induced anthocyanin accumulation and the sugar-inhibited primary root growth, suggesting BIG is an important component of the sugar signaling pathway. Then we found that big mutant plants had higher sugar levels compared with the wild type, indicating the involvement of BIG gene in regulating plant sugar homeostasis. Importantly, we also found that the relative ratio of carbon to nitrogen (C/N) was greatly enhanced by BIG deficiency. Overall, our work expands the known functionality of BIG and reveals its role in regulating sugar response and C/N balance. It is likely that BIG connects nutrient, light, and hormone signaling networks for regulating plant development and adaptive responses.

Resistance to chemotherapy remains a significant problem in the treatment of breast cancer, especially for triple-negative breast cancer (TNBC), in which standard systemic therapy is currently limited to chemotherapeutic agents. Our study aimed to better understand the molecular mechanisms that lead to failure of chemotherapy in TNBC. Herein, we observed elevated expression of Notch1 and major vault protein (MVP) in MDA-MB-231DDPR cells compared to their parental counterparts. We demonstrated that Notch1 could positively regulate the expression of MVP. Also, Notch1 intracellular domain (ICD) was capable of binding to CBF-1 on the promoter of MVP to drive its transcription, resulting in activation of AKT pathway and promoting the progress of epithelial to mesenchymal transition (EMT). Conversely, silencing of Notch1 and MVP suppressed AKT pathway, reduced EMT and enhanced the sensitivity of TNBC cells to cisplatin and doxorubicin. Survival analysis indicated that the MVP was closely related to shorter recurrence-free survival (RFS) in patients with TNBC. Collectively, this study provides evidence that Notch1 activates AKT pathway and promotes EMT partly through direct activation of MVP. Targeting Notch1/MVP pathway appears to have potential in overcoming chemoresistance in TNBC., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Arabidopsis BIG (AtBIG) gene encodes an enormous protein that is required for auxin transport. Loss of AtBIG function not only profoundly changes plant architecture but also alters plant adaptability to environmental stimuli. A putative homolog of AtBIG exists in the rice genome, but no function has been ascribed to it. In this study, we focus on the characterization of the gene structure and function of OsBIG. Sequence and phylogenetic analysis shows that the homologs of OsBIG have high amino acid conservation in several domains across species. Transgenic rice plants in which the expression of OsBIG was disrupted through the CRISPR/Cas9 system-mediated genome editing were used for phenotypic analysis. The Osbig/- plants show high levels of cell death, enhanced electrolyte leakage and membrane lipid peroxidation, and reduced chlorophyll content, which likely accounted for the seedling lethality. Moreover, gene expression between Osbig/- and wild-type plants analyzed by RNA-seq indicates that a number of metabolic and hormonal pathways including ribosome, DNA replication, photosynthesis, and chlorophyll metabolism were significantly perturbed by OsBIG deficiency. In summary, OsBIG gene is integral to the normal growth and development in rice., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

AT-rich interaction domain 4A (ARID4A) and AT-rich interaction domain 4B (ARID4B), which are both the AT-rich interaction domain (ARID) family, have been reported to be oncogene or tumor suppressor gene in various human malignances, but there is no involvement about their functions in prostate cancer (PCa). Our previous study has reported that microRNA-30d (miR-30d) expression can predicted poor clinical prognosis in PCa, however, the underlying mechanisms of miR-30d have not been fully described. The aim of our study is to investigate the expression relevance between miR-30d and ARID4A or ARID4B, and examine the clinical significance and biological function of ARID4A and AIRD4B in PCa. In this study, both ARID4A and ARID4B were identified as the target genes of miR-30d. In addition, the mRNA expression of miR-30d in PCa tissues were significantly negative correlated with ARID4A (Pearson correlation coefficient = -0.313, P = 0.001) and ARID4B (Pearson correlation coefficient = -0.349, P < 0.001), while there was a positive correlation between ARID4A and ARID4B (Pearson correlation coefficient = 0.865, P < 0.001). Moreover, both ARID4A and ARID4B were significantly downregulated in PCa tissues with high Gleason scores (P = 0.005, P = 0.033), PSA failure (P = 0.012, P = 0.05) and short biochemical recurrent-free survival (P = 0.033, P = 0.031). Furthermore, the knockout expression of ARID4A and ARID4B promoted PCa cell proliferation, migration and invasion in vitro. In conclusion, our results indicated that ARID4A and ARID4B may serve as tumor suppressor in PCa progression, suggesting that they might be the potential therapeutic targets in prostate cancer., (© 2018 Wiley Periodicals, Inc.)

Notch3 and GATA binding protein 3 (GATA-3) have been, individually, shown to maintain luminal phenotype and inhibit epithelial-mesenchymal transition (EMT) in breast cancers. In the present study, we report that Notch3 expression positively correlates with that of GATA-3, and both are associated with estrogen receptor-α (ERα) expression in breast cancer cells. We demonstrate in vitro and in vivo that Notch3 suppressed EMT and breast cancer metastasis by activating GATA-3 transcription. Furthermore, Notch3 knockdown downregulated GATA-3 and promoted EMT; while overexpression of Notch3 intracellular domain upregulated GATA-3 and inhibited EMT, leading to a suppression of metastasis in vivo. Moreover, inhibition or overexpression of GATA-3 partially reversed EMT or mesenchymal-epithelial transition induced by Notch3 alterations. In breast cancer patients, high GATA-3 expression is associated with higher Notch3 expression and lower lymph node metastasis, especially for hormone receptor (HR) positive cancers. Herein, we demonstrate a novel mechanism whereby Notch3 inhibit EMT by transcriptionally upregulating GATA-3 expression, at least in part, leading to the suppression of cancer metastasis in breast cancers. Our findings expand our current knowledge on Notch3 and GATA-3's roles in breast cancer metastasis.

Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor prognosis compared with luminal subtype breast cancer. MicroRNA-221 and -222 (miR-221/222) are overexpressed in BLBC and associate with metastasis as well as poor prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs remain unknown. Here, we report that miR-221/222 expression is inversely correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to be overexpressed in luminal breast cancer cells and inhibits epithelial to mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by binding to its 3' untranslated region and suppressing protein translation. Ectopic expression of miR-221/222 significantly promotes EMT, whereas overexpression of Notch3 intracellular domain attenuates the oncogenic function of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by negatively regulating Notch3. Taken together, our results elucidated that miR-221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting that miR-221/222 can serve as a potential therapeutic target in BLBC., Competing Interests: The authors declare no competing interests.

We conducted an infrared thermal imaging-based genetic screen to identify Arabidopsis mutants displaying aberrant stomatal behavior in response to elevated concentrations of CO 2 . This approach resulted in the isolation of a novel allele of the Arabidopsis BIG locus (At3g02260) that we have called CO 2 insensitive 1 (cis1). BIG mutants are compromised in elevated CO 2 -induced stomatal closure and bicarbonate activation of S-type anion channel currents. In contrast with the wild-type, they fail to exhibit reductions in stomatal density and index when grown in elevated CO 2 . However, like the wild-type, BIG mutants display inhibition of stomatal opening when exposed to elevated CO 2 . BIG mutants also display wild-type stomatal aperture responses to the closure-inducing stimulus abscisic acid (ABA). Our results indicate that BIG is a signaling component involved in the elevated CO 2 -mediated control of stomatal development. In the control of stomatal aperture by CO 2 , BIG is only required in elevated CO 2 -induced closure and not in the inhibition of stomatal opening by this environmental signal. These data show that, at the molecular level, the CO 2 -mediated inhibition of opening and promotion of stomatal closure signaling pathways are separable and BIG represents a distinguishing element in these two CO 2 -mediated responses., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)