A multicenter prospective study of lateral neck lymph node mapping in papillary thyroid cancer.

Background: Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation. Methods: We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed. Results: A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively. Conclusions: It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.

A translational regulator MHZ9 modulates ethylene signaling in rice.

Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through analysis of an ethylene-response mutant mhz9, we identified a glycine-tyrosine-phenylalanine (GYF) domain protein MHZ9, which positively regulates ethylene signaling at translational level in rice. MHZ9 is localized in RNA processing bodies. The C-terminal domain of MHZ9 interacts with OsEIN2, a central regulator of rice ethylene signaling, and the N-terminal domain directly binds to the OsEBF1/2 mRNAs for translational inhibition, allowing accumulation of transcription factor OsEIL1 to activate the downstream signaling. RNA-IP seq and CLIP-seq analyses reveal that MHZ9 associates with hundreds of RNAs. Ribo-seq analysis indicates that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene. Our study identifies a translational regulator MHZ9, which mediates translational regulation of genes in response to ethylene, facilitating stress adaptation and trait improvement in rice.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

The effect of sodium hyaluronate on tear film stability in patients with dry eye syndrome after cataract surgery.

BACKGROUND: This study aimed to observe the changes in the ocular surface after phacoemulsification in patients with age-related cataracts with respect to the addition of varying concentrations of hyaluronate. METHODS: Patients with dry eye syndrome were treated with 0.3% and 0.1% sodium hyaluronate eye drops to evaluate the clinical improvement in each treatment group. A total of 73 patients (91 eyes) with age-related cataracts suffering from dry eye syndrome after phacoemulsification were divided into treatment group A (30 eyes), undergoing conventional therapy and treatment with 0.3% sodium hyaluronate; treatment group B (31 eyes), undergoing conventional therapy and treatment with 0.1% sodium hyaluronate; and the control group (group C; 30 eyes), undergoing conventional therapy only. Two groups were given different concentrations of sodium hyaluronate eye drops four times a day (should be completed between 8 AM and 8 PM), one drop at a time. RESULTS: Seven days, 2 weeks, 1 month, and 2 months postoperatively, there were significant differences in the Schirmer I test (SIt), first noninvasive tear film break-up time (NIBUTf), average noninvasive tear film break-up time (NIBUTav), tear meniscus height (TMH), and irregularity (when the refractive force of different parts of different meridians on the same meridian is different. The main manifestation is that the two meridians on the anterior surface of the cornea do not show a 90-degree vertical distribution, which cannot be corrected by conventional astigmatism lenses) between the three groups (p < 0.05). When compared with group C, there were significant differences in the SIt, NIBUTf, NIBUTav, TMH, and irregularity of group A and group B (p < 0.05). When compared with group B, there were significant improvements in the SIt, NIBUTf, NIBUTav, and TMH in group A (p < 0.05). CONCLUSIONS: In the early stage after phacoemulsification, the stability of the tear film is reduced. Adding sodium hyaluronate eye drops can restore tear film structure and improve corneal surface regularity, and a 0.3% solution of sodium hyaluronate eye drops is more effective than a 0.1% solution.

Ethylene-mediated regulation of coleoptile elongation in rice seedlings.

Rice is an important food crop in the world and the study of its growth and plasticity has a profound influence on sustainable development. Ethylene modulates multiple agronomic traits of rice as well as abiotic and biotic stresses during its lifecycle. It has diverse roles, depending on the organs, developmental stages and environmental conditions. Compared to Arabidopsis (Arabidopsis thaliana), rice ethylene signalling pathway has its own unique features due to its special semiaquatic living environment and distinct plant structure. Ethylene signalling and responses are part of an intricate network in crosstalk with internal and external factors. This review will summarize the current progress in the mechanisms of ethylene-regulated coleoptile growth in rice, with a special focus on ethylene signaling and interaction with other hormones. Insights into these molecular mechanisms may shed light on ethylene biology and should be beneficial for the genetic improvement of rice and other crops.

Rice EIL1 interacts with OsIAAs to regulate auxin biosynthesis mediated by the tryptophan aminotransferase MHZ10/OsTAR2 during root ethylene responses.

Ethylene plays essential roles in adaptive growth of rice (Oryza sativa). Understanding of the crosstalk between ethylene and auxin (Aux) is limited in rice. Here, from an analysis of the root-specific ethylene-insensitive rice mutant mao hu zi 10 (mhz10), we identified the tryptophan aminotransferase (TAR) MHZ10/OsTAR2, which catalyzes the key step in indole-3-pyruvic acid-dependent Aux biosynthesis. Genetically, OsTAR2 acts downstream of ethylene signaling in root ethylene responses. ETHYLENE INSENSITIVE3 like1 (OsEIL1) directly activated OsTAR2 expression. Surprisingly, ethylene induction of OsTAR2 expression still required the Aux pathway. We also show that Os indole-3-acetic acid (IAA)1/9 and OsIAA21/31 physically interact with OsEIL1 and show promotive and repressive effects on OsEIL1-activated OsTAR2 promoter activity, respectively. These effects likely depend on their EAR motif-mediated histone acetylation/deacetylation modification. The special promoting activity of OsIAA1/9 on OsEIL1 may require both the EAR motifs and the flanking sequences for recruitment of histone acetyltransferase. The repressors OsIAA21/31 exhibit earlier degradation upon ethylene treatment than the activators OsIAA1/9 in a TIR1/AFB-dependent manner, allowing OsEIL1 activation by activators OsIAA1/9 for OsTAR2 expression and signal amplification. This study reveals a positive feedback regulation of ethylene signaling by Aux biosynthesis and highlights the crosstalk between ethylene and Aux pathways at a previously underappreciated level for root growth regulation in rice.

Small-cell carcinoma of the prostate with negative CD56, NSE, Syn, and CgA indicators: A case report.

BACKGROUND: Small-cell carcinoma of the prostate (SCCP) is a clinically rare malignant tumor, accounting for < 1% of all prostate tumors. However, negativity for all SCCP neuroendocrine markers is rare. Herein, we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features, thus improving the understanding of its clinical diagnosis and management. CASE SUMMARY: We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators. Dysuria was the first symptom, and rectal examination revealed a hard prostate, palpable nodules, diffuse prostate enlargement, no pressure pain, no blood staining in the finger sleeve, 1.33 ng/mL total prostate-specific antigen level, and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL. Ultrasound suggested a prostate size of 5.3 cm × 5.8 cm × 5.6 cm, and magnetic resonance imaging suggested prostate cancer. The lower posterior bladder wall, rectal mesentery, and bilateral seminal vesicles were invaded, with multiple lymph node metastases in the pelvis. A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases. Head and lungs computed tomography revealed no significant nodal shadow. Following a pathological diagnosis of SCCP after a prostate puncture, with negative indicators of common sensitive neuroendocrine staining, chemotherapy was administered; the patient died 4-5 mo after SCCP diagnosis. CONCLUSION: SCCP is a rare disease characterized by atypical clinical symptoms, limited treatment options, a short survival period, and a poor prognosis.

Protective effect of mesenchymal stem cell-derived exosomal treatment of hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury.

BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P<0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P<0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P<0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK, DJ1, LRRK2, Mfn-1, Mfn-2, and OPA1. The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons. CONCLUSIONS: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

Primary adrenal diffuse large B-cell lymphoma with normal adrenal cortex function: A case report.

BACKGROUND: Diffuse large B-cell lymphoma, which accounts for about approximately 30% to 40% of non-Hodgkin's lymphomas, is the most common type and is a class of aggressive B-cell lymphomas. However, diffuse large B-cell lymphomas primary to the adrenal gland are rare. CASE SUMMARY: A 73-year-old man was admitted with abdominal pain and fatigue. After admission, enhanced adrenal computed tomography indicated irregular masses on both adrenal glands, with the larger one on the left side, approximately 8.0 cm × 4.3 cm in size. The boundary was irregular, and surrounding tissues were compressed. No obvious enhancement was observed in the arterial phase. Resection of the left adrenal gland was performed. Pathological diagnosis revealed diffuse large B-cell lymphoma. After surgery, the patient received R-CHOP immunochemotherapy. During the fourth immunochemotherapy, patient condition deteriorated, and he eventually died of respiratory failure. CONCLUSION: R-CHOP is the conventional immunochemotherapy for primary adrenal diffuse large B-cell lymphoma. Surgery is mainly used to diagnose the disease. Hence, the ideal treatment plan remains to be confirmed.

Ethylene signaling in rice and Arabidopsis: New regulators and mechanisms.

Ethylene is a gaseous hormone which plays important roles in both plant growth and development and stress responses. Based on studies in the dicot model plant species Arabidopsis, a linear ethylene signaling pathway has been established, according to which ethylene is perceived by ethylene receptors and transduced through CONSTITUTIVE TRIPLE RESPONSE 1 (CTR1) and ETHYLENE-INSENSITIVE 2 (EIN2) to activate transcriptional reprogramming. In addition to this canonical signaling pathway, an alternative ethylene receptor-mediated phosphor-relay pathway has also been proposed to participate in ethylene signaling. In contrast to Arabidopsis, rice, a monocot, grows in semiaquatic environments and has a distinct plant structure. Several novel regulators and/or mechanisms of the rice ethylene signaling pathway have recently been identified, indicating that the ethylene signaling pathway in rice has its own unique features. In this review, we summarize the latest progress and compare the conserved and divergent aspects of the ethylene signaling pathway between Arabidopsis and rice. The crosstalk between ethylene and other plant hormones is also reviewed. Finally, we discuss how ethylene regulates plant growth, stress responses and agronomic traits. These analyses should help expand our knowledge of the ethylene signaling mechanism and could further be applied for agricultural purposes.

Efficacy of bone marrow stem cells combined with core decompression in the treatment of osteonecrosis of the femoral head: A PRISMA-compliant meta-analysis.

BACKGROUND: This study used the meta-analytic approach to assess the safety and treatment efficacy of bone marrow stem cells (BMSCs) with core decompression (CD) for osteonecrosis of the femoral head (ONFH) based on randomized controlled trials (RCTs). METHODS: Electronic database of PubMed, Embase, Google Scholar, China National Knowledge Infrastructure (CNKI), and Wanfang database was searched up to December 26, 2019 for relevant RCTs about combined utilization of BMSCs and CD versus CD alone for ONFH. Gray literature sources were also searched. We conducted a meta-analysis following the guidelines of the Cochrane Reviewer's Handbook. Two independent reviewers performed the data extraction and assessed study quality. Our outcomes included the Harris hip scores (HHS) at 12 months, HHS at 24 months, necrotic area of femoral head, conversion to total hip arthroplasty (THA), visual analog pain scale at final follow-up, and adverse effects. The meta-analysis was performed with Stata 12.0. RESULTS: A total of 15 published studies with 688 patients fulfilled the requirements of inclusion criteria. Across all populations, participants in combined utilization of BMSCs group showed a statistical significance with higher HHS at 12 months (standard mean difference [SMD] 0.53, 95% confidence interval [CI] 0.29-0.77) and 24 months (SMD 0.57, 95% CI 0.36-0.77). Similarly, participants in combined utilization of BMSCs group had more advantages in reducing necrotic area of femoral head (SMD -1.05, 95% CI -1.73 to -0.38) and the rate of conversion to THA (risk ratio [RR] = 0.53, 95% CI 0.38-0.74, P = .000). No significant differences were identified regarding postoperative adverse effects postoperatively (RR = 1.03, 95% CI 0.64-1.67, P = .893). CONCLUSION: Compared with CD treated alone in the treatment of ONFH, combined utilization of CD and autologous BMSCs implantation has a better pain relief and clinical outcomes and can delay the collapse of the femoral head more effectively.

The GDSL Lipase MHZ11 Modulates Ethylene Signaling in Rice Roots.

Ethylene plays important roles in plant growth and development, but the regulation of ethylene signaling is largely unclear, especially in crops such as rice (Oryza sativa). Here, by analysis of the ethylene-insensitive mutant mao huzi 11 (mhz11), we identified the GDSL lipase MHZ11, which modulates ethylene signaling in rice roots. MHZ11 localized to the endoplasmic reticulum membrane and has acyl-hydrolyzing activity. This activity affects the homeostasis of sterols in rice roots and is required for root ethylene response. MHZ11 overexpression caused constitutive ethylene response in roots. Genetically, MHZ11 acts with the ethylene receptor ETHYLENE RESPONSE SENSOR2 (OsERS2) upstream of CONSTITUTIVE TRIPLE RESPONSE2 (OsCTR2) and ETHYLENE INSENSITIVE2 (OsEIN2). The mhz11 mutant maintains more OsCTR2 in the phosphorylated form whereas MHZ11 overexpression promotes ethylene-mediated inhibition of OsCTR2 phosphorylation. MHZ11 colocalized with the ethylene receptor OsERS2, and its effect on OsCTR2 phosphorylation requires ethylene perception and initiation of ethylene signaling. The mhz11 mutant overaccumulated sterols and blocking sterol biosynthesis partially rescued the mhz11 ethylene response, likely by reducing receptor-OsCTR2 interaction and OsCTR2 phosphorylation. We propose that MHZ11 reduces sterol levels to impair receptor-OsCTR2 interactions and OsCTR2 phosphorylation for triggering ethylene signaling. Our study reveals a mechanism by which MHZ11 participates in ethylene signaling for regulation of root growth in rice.

Histidine kinase MHZ1/OsHK1 interacts with ethylene receptors to regulate root growth in rice.

Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation.

Doxycycline alleviates paraquat-induced acute lung injury by inhibiting neutrophil-derived matrix metalloproteinase 9.

Paraquat (PQ), a highly toxic herbicide, selectively accumulates in the lungs and causes pulmonary damage through oxidative and inflammatory processes after intentional or accidental poisoning. The resulting acute lung injury (ALI) is characterized by neutrophil infiltration and extensive inflammation with rapid respiratory failure. However, effective therapies are lacking. We tested the hypothesis that suppressing neutrophil-derived matrix metalloproteinase 9 (MMP9) would ameliorate the inflammatory milieu and alleviate PQ-induced ALI. Lung injury was assessed in mice intratracheally injected with PQ aerosol by measuring the lung static compliance, cell count and neutrophil percentage of the bronchoalveolar lavage fluid (BALF) and lung, alveolar-capillary permeability, and histopathological lung injury scores. MMP9/2 activity was assessed by gelatin zymography, and the location of neutrophils and MMP9 in the lung was evaluated by immunofluorescence costaining. In the neutrophil depletion experiment, mice received anti-Ly6G antibody intraperitoneally; for the MMP inhibition experiment, an MMP inhibitor, doxycycline (DOX), was administered by gavage. In PQ-induced ALI, the activity of neutrophil-derived MMP9 but not MMP2 increased significantly. Neutrophil depletion reduced the inflammatory burden, improved pulmonary edema, and reduced the PQ-induced overexpression of MMP9. Consistently, oral delivery of DOX to mice decreased the overexpression of MMP9 that was activated by PQ and phenocopied the resolution of PQ-induced ALI observed after neutrophil depletion. Taken together, our results show for the first time that DOX is involved in the resolution of PQ-induced ALI via a mechanism involving reducing the activity of neutrophil-derived MMP9. We speculate that DOX may represent a novel therapeutic strategy for PQ-induced ALI.

Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) prior to surgery is a standard therapy for locally advanced rectal cancer, but the optimum regime is not conclusive. This meta-analysis evaluated various CRT regimens with regard to the rate of pathologic complete response (pCR) and toxic effects of grade ≥3. METHODS: The databases PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs) that compared neoadjuvant CRT regimes for treating patients with locally advanced rectal cancer, published before 28 December 2017. The primary end points were pCR and toxic effects. A network meta-analysis was applied. RESULTS: Fourteen RCTs (with 5,599 participants) involving the following eight regimens were included: fluorouracil (5FU) alone, or 5FU with oxaliplatin (OXA), cisplatin, or irinotecan (CPT-11); capecitabine (CAP) alone, or CAP with OXA or CPT-11; and CPT-11 with combined tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. The rate of pCR associated with CAP + OXA was significantly higher compared with 5FU alone; there were no significant differences among the other regimens. The toxicity of 5FU + OXA or CAP + OXA was significantly worse than that of 5FU alone or CAP alone. CAP + OXA and CAP were ranked, respectively, the most and second most effective regimens in terms of pCR rate. 5FU alone and CAP alone likely had the lowest and second lowest toxicity, respectively. CONCLUSION: Among the currently available CRT regimens for locally advanced rectal cancer, this meta-analysis indicated that CAP + OXA provides the superior clinical results. Adding OXA to 5FU or CAP significantly increases toxicity.

The anti-inflammatory and anti-oxidative effects of conbercept in treatment of macular edema secondary to retinal vein occlusion.

To investigate the effects of conbercept on inflammatory and oxidative response in macular edema secondary to retinal vein occlusion (RVO-ME). Retinal microvasculature were detected by optical coherence tomographic angiography (OCTA). The inflammation related factors including prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), intercellular cell adhesion molecule-1 (ICAM-1) and macrophage inflammatory protein-1 (MIP-1) were determined in human and mice with RVO-ME. OCTA images showed that capillary non-perfusion, enlargement of the foveal avascular zone, telangiectatic vessels and some forms of intraretinal edema in RVO-ME and all these were alleviated by conbercept treatment. PGE1, PGE2, PGF2a, ICAM-1 and MIP-1 in aqueous fluid extracted from RVO-ME patients was significantly increased compared with non-RVO subjects, intravitreal injection of conbercept partly reduced ICAM-1 and MIP-1 levels but not PGE1, PGE2 and PGF2a. The glutathione level was reduced in aqueous fluid extracted from RVO-ME patients but was restored after conbercept treatment. The inflammation, angiogenesis and ROS generation was increased in RVO-ME mice, conbercept partly inhibited these effects. Mechanistically, conbercept inhibited vascular endothelial growth factor (VEGF), ICAM-1, MIP-1, NOX-1 and NOX-4 protein expressions, but not PGE1, PGE2 and PGF2a expressions. Conbercept alleviates RVO-ME through inhibiting inflammation, angiogenesis and oxidative responses. These findings further reveals the molecular mechanism of conbercept for treatment of RVO-ME.

E3 ubiquitin ligase SOR1 regulates ethylene response in rice root by modulating stability of Aux/IAA protein.

Plant hormones ethylene and auxin synergistically regulate plant root growth and development. Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCFTIR1/AFB triggers a transcription-based auxin signaling. Here we show that rice (Oryza sativa L.) soil-surface rooting 1 (SOR1), which is a RING finger E3 ubiquitin ligase identified from analysis of a rice ethylene-insensitive mutant mhz2/sor1-2, controls root-specific ethylene responses by modulating Aux/IAA protein stability. SOR1 physically interacts with OsIAA26 and OsIAA9, which are atypical and canonical Aux/IAA proteins, respectively. SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCFOsTIR1/AFB2-mediated and SOR1-assisted destabilization of OsIAA9 protein. Our study provides a candidate mechanism by which the SOR1-OsIAA26 module acts downstream of the OsTIR1/AFB2-auxin-OsIAA9 signaling to modulate ethylene inhibition of root growth in rice seedlings.