Sexual reproduction requires recognition between the male and female gametes. In flowering plants, the immobile sperms are delivered to the ovule-enclosed female gametophyte by guided pollen tube ...growth. Although the female gametophyte-secreted peptides have been identified to be the chemotactic attractant to the pollen tube, the male receptor(s) is still unknown. Here we identify a cell-surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives female attractant LURE1 in Arabidopsis thaliana. MDIS1, MIK1 and MIK2 are plasma-membrane-localized receptor-like kinases with extracellular leucine-rich repeats and an intracellular kinase domain. LURE1 specifically binds the extracellular domains of MDIS1, MIK1 and MIK2, whereas mdis1 and mik1 mik2 mutant pollen tubes respond less sensitively to LURE1. Furthermore, LURE1 triggers dimerization of the receptors and activates the kinase activity of MIK1. Importantly, transformation of AtMDIS1 to the sister species Capsella rubella can partially break down the reproductive isolation barrier. Our findings reveal a new mechanism of the male perception of the female attracting signals.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Grafting onto pumpkin rootstock is widely applied in cucumber production to improve growth and yield, as well as to overcome soil‐borne diseases and enhance resistance to abiotic stresses. In this ...study, we constructed the cucumber‐pumpkin heterografts with the one‐cotyledon grafting method, and examined the effects of heterografting on biomass allocation and sugar partitioning, with cucumber and pumpkin self‐grafts used as control. Compared with cucumber self‐grafts, heterografting onto pumpkin rootstock promoted photosynthesis in cucumber scion, and led to higher sucrose contents in the 1st true leaf (source) and newly emerged leaf (sink). Thereby, the scion part of heterografts accumulated more biomass than cucumber self‐grafts. In contrast, when compared to pumpkin self‐grafts, grafting with cucumber scion reduced root vigor and biomass but promoted cotyledon growth in pumpkin rootstock. The roots (sink) of heterografts contained less sucrose and hexoses, and showed reduced sucrose synthase (SuSy) and hexokinase (HXK) activities. However, the rootstock cotyledon (source) contained more sucrose and starch, and showed higher activities of HXK, cell‐wall invertase (CWIN), and enzymes for starch synthesis and degradation. Furthermore, removal or shade of rootstock cotyledon led to reduced growth of root and scion. Silencing of CmoMEX1a gene in rootstock cotyledon inhibited maltose export and reduced root growth of heterografts. These results indicated that rootstock cotyledon, especially its starch content, played a buffering role in the growth regulation of cucumber‐pumpkin heterografts. Taken together, our results provided a major contribution to our understanding of source‐sink sugar partitioning and scion‐rootstock growth balancing in cucumber‐pumpkin heterografts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hypocotyl elongation is dramatically influenced by environmental factors and phytohormones. Indole‐3‐acetic acid (IAA) plays a prominent role in hypocotyl elongation, whereas abscisic acid (ABA) is ...regarded as an inhibitor through repressing IAA synthesis and signalling. However, the regulatory role of ABA in local IAA deactivation remains largely uncharacterized. In this study, we confirmed the antagonistic interplay of ABA and IAA during the hypocotyl elongation of tomato (Solanum lycopersicum) seedlings. We identified an IAA oxidase enzyme DIOXYGENASE FOR AUXIN OXIDATION2 (SlDAO2), and its expression was induced by both external and internal ABA signals in tomato hypocotyls. Moreover, the overexpression of SlDAO2 led to a reduced sensitivity to IAA, and the knockout of SlDAO2 alleviated the inhibitory effect of ABA on hypocotyl elongation. Furthermore, an ABA‐responsive regulatory SlAREB1/SlABI3‐1/SlABI5 cascade was identified to act upstream of SlDAO2 and to precisely control its expression. SlAREB1 directly bound to the ABRE present in the SlDAO2 promoter to activate SlDAO2 expression, and SlABI3‐1 enhanced while SlABI5 inhibited the activation ability of SlAREB1 by directly interacting with SlAREB1. Our findings revealed that ABA might induce local IAA oxidation and deactivation via SlDAO2 to modulate IAA homoeostasis and thereby repress hypocotyl elongation in tomato.
Summary statement
We found that ABA regulates expression of IAA oxidase gene SlDAO2 via the AREB1/ABI3‐1/ABI5 transcription factor cascade, and thereby modulating IAA homeostasis and inhibiting hypocotyl elongation in tomato seedlings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Despite zinc finger and BTB domain-containing 7A (ZBTB7A) documented importance in multiple tumors, the function and clinical value in Colorectal cancer (CRC) remain elusive. The aim of this study ...was to evaluate the functional roles and the clinical value of ZBTB7A in CRC progression.
The level of ZBTB7A was detected in a large cohort of CRC patients (n = 189) by immunohistochemistry (IHC), and we analyzed the diagnostic and prognostic value of the protein. In addition, the functional roles of ZBTB7A on CRC were explored in vitro and in vivo.
Survival analyses indicated that patients with high ZBTB7A expression made the prognosis worse (P = 0.024). Functionally, knockdown of ZBTB7A could markedly inhibit tumor proliferation in vitro and in vivo, whereas ZBTB7A overexpression displayed the opposite results.
ZBTB7A was associated with poor survival outcomes and functioned as an oncogene in CRC patients, indicating that it is a potential prognostic biomarker and therapeutic target for CRC patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, ...oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is ...challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS‐RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery.
Materials and Methods
From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS‐RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected.
Results
Of 10 patients, 8 underwent en bloc resection via TORS‐RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS‐related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow‐up of 19 months, only 1 (10%) patient developed cervical recurrence.
Conclusions
TORS‐RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning.
Level of Evidence
4 Laryngoscope, 131:E1895–E1902, 2021
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To compare intensity‐modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II‐IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with ...stage II–IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well‐balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well‐balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3‐year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco‐regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4–4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related‐skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP‐IMRT combination for maximizing survival for patients with stage II‐IVb NPC.
What's new?
Standard treatment for nasopharyngeal carcinoma (NPC) that has spread to lymph nodes in the head and neck entails concurrent cisplatin (CDDP) and intensity‐modulated radiotherapy (IMRT). High toxicity rates, however, limit the utility of this approach. The present study examines an alternative strategy: cetuximab (CTX) and nimotuzumab (NTZ) plus IMRT. No differences in risk of disease progression, relapse, metastasis or death were observed in a direct comparison between CDDP plus IMRT and CTX/NTZ plus IMRT in NPC patients. Both regimens were associated with hematologic toxicities and with toxicities targeting different tissues, warranting further investigation of side effects specific to CTX/NTZ.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In flowering plants, pollen tubes are attracted to the ovule by secreted peptides to release the sperm cells for double fertilization. This process is species-specific and acts as an important stage ...of reproductive isolation between species. Here we identified a cysteine-rich peptide TICKET2 in Arabidopsis thaliana and its orthologs in Arabidopsis lyrata and Capsella rebella that can attract the conspecific pollen tubes, but not the pollen tubes of relative species in Brassicaceae. Genetic knockout of the AtTICKET subclade compromised the pollen tube attraction efficiency. This study identified a new pollen tube attracting signal and shed light on the molecular basis of reproductive isolation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In flowering plants, sperm cells are delivered to the embryo sac by a pollen tube guided by female signals. Both the gametic and synergid cells contribute to pollen tube attraction. Synergids secrete ...peptide signals that lure the tube, while the role of the gametic cells is unknown. Previously, we showed that CENTRAL CELL GUIDANCE (CCG) is essential for pollen tube attraction in Arabidopsis thaliana, but the molecular mechanism is unclear. Here, we identified CCG BINDING PROTEIN1 (CBP1) and demonstrated that it interacts with CCG, Mediator subunits, RNA polymerase II (Pol II), and central cell-specific AGAMOUS-like transcription factors. In addition, CCG interacts with TATA-box Binding Protein 1 and Pol II as a TFIIB-like transcription factor. CBP1- knockdown ovules are defective in pollen tube attraction. Expression profiling revealed that cysteine-rich peptide (CRP) transcripts were downregulated in ccg ovules. CCG and CBP1 coregulate a subset of CRPs in the central cell and the synergids, including the attractant LURE1. CBP1 is extensively expressed in multiple vegetative tissues and specifically in the central cell in reproductive growth. We propose that CBP1, via interaction with CCG and the Mediator complex, connects transcription factors and the Pol II machinery to regulate pollen tube attraction.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Radioresistance-induced local failure, which can result in residual or recurrent tumors, remains one of the major causes of treatment failure in nasopharyngeal carcinoma (NPC). Lipocalin 2 (LCN2) is ...known to play important roles in cancer initiation, progression, and treatment responses. However, its role in the radioresistance of NPC remains unclear.
Microarray data from the Gene Expression Omnibus (GEO) was screened for candidate biomarkers relating to the radioresistance of NPC. The expression of LCN2 in NPC cell lines was verified by quantitative real-time PCR (RT-qPCR) and western blotting. The effects of knockdown or overexpression of LCN2 on NPC radiosensitivity were examined using a soft agar colony formation assay and a
H2AX assay. LCN2 expression in NPC specimens was evaluated by immunohistochemistry. Survival outcomes were analyzed. A possible correlation between LCN2 and hypoxia-inducible factor 1-alpha (HIF-1A) was examined by western blotting and a tissue microarray.
LCN2 was highly expressed in the radioresistant NPC cell line CNE2R. Knocking down LCN2 enhanced the radiosensitivity of NPC cells by impairing their ability to repair DNA damage or proliferate, while ectopic expression of LCN2 conferred additional radioresistance to NPC cells. Immunohistochemical analysis of 100 NPC specimens revealed that LCN2 expression was significantly upregulated in radioresistant NPC tissues and was associated with NPC recurrence. Furthermore, a significant correlation between the expression of LCN2 and HIF-1A was detected.
LCN2 is associated with radioresistance and recurrence in NPC and may facilitate the development of a radioresistant phenotype through interacting with HIF-1A. Our data indicate that LCN2 is a promising target for predicting and overcoming radioresistance in NPC.
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