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Summary: Tetrapyrroles have essential functions as pigments and cofactors during plant growth and development, and the tetrapyrrole biosynthesis pathway is tightly controlled. Multiple organellar RNA editing factors (MORFs) are required for editing of a wide variety of RNA sites in chloroplasts and mitochondria, but their biochemical properties remain elusive.Here, we uncovered the roles of chloroplast‐localized MORF2 and MORF9 in modulating tetrapyrrole biosynthesis and embryogenesis in Arabidopsis thaliana. The lack or reduced transcripts of MORF2 or MORF9 significantly affected biosynthesis of the tetrapyrrole precursor 5‐aminolevulinic acid and accumulation of Chl and other tetrapyrrole intermediates.MORF2 directly interacts with multiple tetrapyrrole biosynthesis enzymes and regulators, including NADPH:PROTOCHLOROPHYLLIDE OXIDOREDUCTASE B (PORB) and GENOMES UNCOUPLED4 (GUN4). Strikingly, MORF2 and MORF9 display holdase chaperone activity, alleviate the aggregation of PORB in vitro, and are essential for POR accumulation in vivo. Moreover, both MORF2 and MORF9 significantly stimulate magnesium chelatase activity.Our findings reveal a previously unknown biochemical property of MORF proteins as chaperones and point to a new layer of post‐translational control of the tightly regulated tetrapyrrole biosynthesis in plants. [ABSTRACT FROM AUTHOR]

Summary: As one of the largest gene families in plants, the cytochrome P450 monooxygenase genes (CYPs) are involved in diverse biological processes including biotic and abiotic stress response. Moreover, P450 genes are prone to expanding due to gene tandem duplication during evolution, resulting in generations of novel alleles with the neo‐function or enhanced function. Here, the bread wheat (Triticum aestivum) gene TaCYP81D5 was found to lie within a cluster of five tandemly arranged CYP81D genes, although only a single such gene (BdCYP81D1) was present in the equivalent genomic region of the wheat relative Brachypodium distachyon. The imposition of salinity stress could up‐regulate TaCYP81D5, but the effect was abolished in plants treated with an inhibitor of reactive oxygen species synthesis. In SR3, a wheat cultivar with an elevated ROS content, the higher expression and the rapider response to salinity of TaCYP81D5 were related to the chromatin modification. Constitutively expressing TaCYP81D5 enhanced the salinity tolerance both at seedling and reproductive stages of wheat via accelerating ROS scavenging. Moreover, an important component of ROS signal transduction, Zat12, was proven crucial in this process. Though knockout of solely TaCYP81D5 showed no effect on salinity tolerance, knockdown of BdCYP81D1 or all TaCYP81D members in the cluster caused the sensitivity to salt stress. Our results provide the direct evidence that TaCYP81D5 confers salinity tolerance in bread wheat and this gene is prospective for crop improvement. [ABSTRACT FROM AUTHOR]

Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7.9 mg crude drug/mL) and SSOJ (12.2 mg crude drug/mL). Meanwhile, FOJ or SSOJ could induce the up-regulation of LC3-II at both protein and mRNA levels. Moreover, we observed the cytoplasmic vaculoes which formed double-layered membranes and only some cytoplasmic organelles or myelin figures remained in FOJ or SSOJ-treated A549 cells for 24 h by Transmission Electron Microscopy (TEM). Further detection about the PI3K/Akt/mTOR signaling pathway showed that the levels of PI3K, Akt and mTOR were significantly suppressed with the FOJ or SSOJ treatment. The 3-MA (an autophagy inhibitor) and LY294002 (a PI3K inhibitor) further confirmed the underlying mechanism in the FOJ or SSOJ-induced autophagy of A549 cells. Additionally, the pretreatment with FOJ and SSOJ increased the level of p53, whereas decreased the expression of Ki67. These findings suggested that FOJ or SSOJ could activate the autophagy of A549 cells, wherein the mechanism might be associated with their inhibition of PI3K/Akt/mTOR signaling pathway. Thus, FOJ or SSOJ could be a potential autophagy inducer to prevent the process of lung cancer. [ABSTRACT FROM AUTHOR]

This work investigates how heat treatment temperature and atmosphere would affect the physicochemical properties and oxidation behaviour of Zhundong lignite (ZD). Samples of ZD were firstly heated at 150–400 °C in either N2 or simulated flue gas (FG) atmosphere, which were then analysed to obtain their mass losses, elemental composition, oxygen-containing functional groups (OCFGs) and water re-adsorption capacities. Results showed that the dried ZD subjecting to N2 atmosphere had a mass loss of 9.90 mass%–10.95 mass% at 150–250 °C, but further increased to 25.17 mass% at 400 °C, leading to an increase in C/O ratios from 2.49 to 4.70 as treatment temperature increased. FTIR analysis revealed that OCFGs including hydroxyl, carboxyl, carbonyl and ether bond decreased as heat treatment temperature increased, which also deceased the water re-absorption capacity of heat-treated ZDs. While it is heated in FG, the mass loss of ZDs at temperatures below 300 °C was roughly equivalent to those in N2, but was less than those at 350–400 °C, due to the incorporation of O along with increased OCFGs peak intensities at these temperatures. This also allowed for the re-absorption of more moisture than those samples treated in N2. In addition, the combustion reactivity of the heat-treated ZDs was enhanced and the combustion process turned into higher temperature zone with increasing treatment temperature, suggesting that the variation in physicochemical properties of heat-treated ZDs also affected their oxidation behaviour. [ABSTRACT FROM AUTHOR]

Introduction: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. Methods: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. Results: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77–13.2; p = 0.002). Conclusion: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations. [ABSTRACT FROM AUTHOR]

Chloroplasts produce singlet oxygen (1O2), which causes changes in nuclear gene expression through plastid-to-nucleus retrograde signaling to increase plant fitness. However, the identity of this 1O2-triggered pathway remains unclear. Here, we identify mutations in GENOMES UNCOUPLED4 (GUN4) and GUN5 as suppressors of phytochrome-interacting factor1 (pif1) pif3 in regulating the photo-oxidative response in Arabidopsis thaliana. GUN4 and GUN5 specifically interact with EXECUTER1 (EX1) and EX2 in plastids, and this interaction is alleviated by treatment with Rose Bengal (RB) or white light. Impaired expression of GUN4, GUN5, EX1, or EX2 leads to insensitivity to excess light and overexpression of EX1 triggers photo-oxidative responses. Strikingly, upon light irradiation or RB treatment, EX1 transiently accumulates in the nucleus and the nuclear fraction of EX1 shows a similar molecular weight as the plastid-located protein. Point mutagenesis analysis indicated that nuclear localization of EX1 is required for its function. EX1 acts as a transcriptional co-activator and interacts with the transcription factors WRKY18 and WRKY40 to promote the expression of 1O2-responsive genes. This study suggests that EX1 may act in plastid-to-nucleus signaling and establishes a 1O2-triggered retrograde signaling pathway that allows plants adapt to changing light environments during chloroplast development. EX1 acts as a plastid-to-nucleus mobile protein that relays 1O2 signals, thus bridging the communication gap between plastids and the nucleus. [ABSTRACT FROM AUTHOR]

Cigarette smoke is the leading cause of the development of various lung diseases including lung cancer through triggering oxidant stress and inflammatory responses which contributed to the lesions of normal human bronchial epithelial (NHBE) cell. Wedelolactone (WEL), a natural compound from Eclipta prostrata L., has been found to possess the inhibitive effects on the proliferation and growth of cancers. In the present study, we investigated the effects of WEL on NHBE cell injury induced by cigarette smoke extract (CSE) in vitro . It showed that the pretreatment WEL (2.5–20 μM) resulted in a significant protective effect on 10% CSE-induced cell death in NHBE cells. The pretreatment with WEL dose-dependently and significantly reversed the activities of SOD, CAT, GSH and the level of MDA to normal level. We also found that the protein expression levels of COX-2 and ICAM-1 which are related to inflammatory response were remarkably reduced by WEL compared with 10% CSE treatment. Additionally, WEL also reduced the expressions of antioxidases including NAD(P)H dehydrogenase:Quinone 1 (NQO1) and heme oxygenase-1 (HO-1). Moreover, Nrf2 inhibitor all-trans-retinoic acid (ATRA) decreased remarkably their expressions. These results suggest that WEL protects NHBE cell against CSE-induced injury through modulating Nrf2 pathway. Our study indicates that WEL may be a new potential protective agent against CSE-induced lung injury. [ABSTRACT FROM AUTHOR]

Background: A predictive model for acquired premature ejaculation (APE) in PE patients has not yet been established. Objectives: This study was aimed at determining which factors were independently associated with the possibility of predicting APE in PE patients, and whether an effective pre‐treatment nomogram for predicting their individual chances of being APE in PE patients can be developed. Materials and methods: We analyzed the medical histories of 915 PE patients diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) between May 2019 and May 2020. The diagnostic nomogram was developed using a multivariate logistic regression model by integrating selected significant variables determined through univariate analysis. Receiver operating characteristic curves were used to measure the predictive accuracy of the nomogram and its constituted variables, and calibrations were performed by making a comparison of nomogram‐predicted probability with actual rate of APE. Results: The independent predictors for APE that were identified include Age, Intra‐vaginal Ejaculation Latency Time (IELT), Frequency of sexual desire (FSD), and Eysenck Personality Questionnaire‐Revised Short Scale for Chinese (psychoticism) [EPQ‐RSC(P)] scores. The predictive accuracy of the nomogram was 0.782 (95% CI: 0.723–0.841). Also, excellent agreement was demonstrated between the nomogram‐predicted probability and the actual rate of APE. Discussion and conclusion: We identified 4 independent predictors for APE and demonstrated the potential significant differences in psychoticism between LPE and APE patients. This was the first internally validated predictive APE nomogram where good discrimination and calibration were applied, and it offers a promising role in clinical practice. More studies are necessary for verification of its universal applicability. [ABSTRACT FROM AUTHOR]

SUMMARY: Plants experiencing abiotic stress react by generating reactive oxygen species (ROS), compounds that, if allowed to accumulate to excess, repress plant growth and development. Anthocyanins induced by abiotic stress are strong antioxidants that neutralize ROS, whereas their over‐accumulation retards plant growth. Although the mechanism of anthocyanin synthesis has been revealed, how plants balance anthocyanin synthesis under abiotic stress to maintain ROS homeostasis is unknown. Here, ROS‐related proteins, SIMILAR TO RCD‐ONEs (SROs), were analysed in Zea mays (maize), and all six SRO1 genes were inducible by a variety of abiotic stress agents. The constitutive expression of one of these genes, ZmSRO1e, in maize as well as in Arabidopsis thaliana increased the sensitivity of the plant to abiotic stress, but repressed anthocyanin biosynthesis and ROS scavenging activity. Loss‐of‐function mutation of ZmSRO1e enhanced ROS tolerance and anthocyanin accumulation. We showed that ZmSRO1e competed with ZmR1 (a core basic helix‐loop‐helix subunit of the MYB–bHLH–WD40 transcriptional activation complex) for binding with ZmPL1 (a core MYB subunit of the complex). Thus, during the constitutive expression of ZmSRO1e, the formation of the complex was compromised, leading to the repression of genes, such as ZmA4 (encoding dihydroflavonol reductase), associated with anthocyanin synthesis. Overall, the results have revealed a mechanism that allows the products of maize SRO1e to participate in the abiotic stress response. Significance Statement: The SRO family is a plant‐specific group of proteins involved in the abiotic stress response, but the function and molecular mechanisms of maize SRO proteins in abiotic stress are unclear. In this study, we found that ZmSRO1e, the most stress responsive of all maize SROs, repressed anthocyanin synthesis and was involved in the maintenance of ROS homeostasis, which is important for balancing plant growth and abiotic stress tolerance. [ABSTRACT FROM AUTHOR]

Although the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine. To investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI. Data of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations. The primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study. Patients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702–0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations. If the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment. This study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions. This study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool. Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341–2350. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a prognostic nomogram for patients with intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for non-metastatic upper tract urothelial carcinoma (UTUC). Methods: The clinical data of 468 patients registered in the surveillance, epidemiology and end results database between 2010 and 2015 were retrospectively analyzed. Multivariate analysis using the Cox proportional hazard model was used to determine independent prognostic factors for the development of a nomogram to predict the 1-, 3-, and 5-year probability of individual cancer-specific survival (CSS). Moreover, the nomogram was internally validated using receiver operating characteristic curves and calibration plots. Results: Age at IVR > 80 years, UTUC stage ≥ T3, bladder cancer (BC) stage T1, and muscle-invasive BC (stage ≥ T2) were identified as independent risk factors for CSS in patients with IVR after RNU, whereas a time interval of > 24 months between UTUC and BC was an independent protective factor. The 1-, 3-, and 5-year predictive accuracies of our nomogram were 0.74, 0.70, and 0.71, respectively. Additionally, 1-, 3-, and 5-year calibration curves demonstrated perfect agreement between the nomogram-predicted and the actual CSS. Conclusions: This study developed and internally validated the first nomogram to date to predict individual prognosis in patients with IVR after RUN for UTUC. This nomogram can be used for patient counseling and for designing clinical trials. [ABSTRACT FROM AUTHOR]

Objective: The only one established prognostic nomogram for patients with sarcomatoid renal cell carcinoma (sRCC) was based on a small sample-sized study without external validation, and a nomogram can be applied to western sRCC patients has not yet been developed. Therefore, our study aimed to construct and validate an effective nomogram to predict overall survival (OS) for these patients. Methods: The independent predictors for OS were identified and the nomogram was constructed on the basis of a retrospective study of a training cohort consisted of 428 non-Hispanic white sRCC patients registered in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. Then, the discriminative performance of the nomogram was assessed by the concordance index (C-index). OS calibrations of the nomogram were also performed by comparing the nomogram-predicted probability to the observed survival rate. Furthermore, our nomogram was externally validated using two independent cohorts consisted of 71 non-Hispanic black patients and 82 Hispanic patients, respectively. Results: Age at diagnosis, T stage, N stage, bone metastases, liver metastases, lung metastases and nephrectomy were identified as independent predictors for OS. In the training cohort and two validation cohorts, the C-indexes of the nomogram were 0.737, 0.801 and 0.764, respectively. Besides, excellent agreements between the nomogram prediction and the actual observation were achieved in all cohorts. Conclusions: The current study constructed and validated an effective prognostic nomogram for patients with sRCC, which can be used to perform accurate predictions of the 0.5-, 1-, and 2-year possibilities of OS. [ABSTRACT FROM AUTHOR]

Background: Renal interstitial fibrosis is a common pathway of chronic kidney disease to end-stage renal disease, which is characterized by an imbalance between the synthesis and degradation of the collagen-rich extracellular matrix (ECM). While, discoidin domain receptor 2 (DDR2) can be activated when it binds to some types of collagen. Therefore, we hypothesized that DDR2 may be a major player in renal interstitial fibrosis. Methods: Renal histologic analysis, real-time PCR analyses and hydroxyproline assay were performed in DDR2-deficient mice and wild-type mice after unilateral ureteral obstruction; C57 mice were randomly divided into sham operation group (Sham group, n = 4), renal interstitial fibrosis model group (UUO group, n = 4), and calcium dobesilate treatment group (CDT group, n = 4), preparation of renal interstitial fibrosis model by unilateral ureteral obstruction (UUO), CDT Group was treated with calcium dobesilate orally, Sham group and UUO group were given double distilled water, HE staining, Masson staining, real-time quantitative PCR were detected after 14 days of UUO in mice to observe the renal interstitial fibrosis degree. Results: DDR2 expression was dramatically increased in the obstructed kidney; In contrast to wild-type mice that developed severe interstitial fibrosis, the DDR2-deficient mice displayed only moderate fibrotic changes; Compared with the UUO group, the degree of renal interstitial fibrosis in CDT group was relieved after operation 14 day. Conclusion: DDR2 might play an important role in the development of RIF; Calcium dobesilate can affect the expression of DDR2 and improve the renal interstitial fibrosis in mice. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) has a crucial role in prostate cancer. RNA‑binding protein‑mediated post‑transcriptional regulation is important in the initiation and development of cancer. The present study attempted to elucidate the mutual association of AR and RNA‑binding protein quaking (QKI) in the development of prostate cancer. Dual‑luciferase reporter demonstrated that AR can positively regulate the expression of QKI in prostate cancer cell lines due to its effective transcription regulating function. In addition, QKI may increase expression of AR by heat shock protein 90, which is a coactivator of AR, and silencing QKI can increase the sensitive of Casodex, which is an antagonist of AR in castration‑resistant prostate cancer. This may be a new strategy for advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Tumor vascular normalization involved in immune response is beneficial to the chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC). However, its vascular normalization in HCC and the role of the immune response in angiogenesis were unclear. In the present study, effects of Endostar on tumor vascular normalization were evaluated in hepatoma 22 (H22) tumor‑bearing mice. Endostar was able to inhibit the proliferation and infiltration of tumor cells and improve α‑fetoprotein, tumor necrosis factor‑α and cyclic adenosine 5'‑phosphate levels in the serum of H22‑bearing mice, as well as the protein expression levels of the immune factors interferon‑γ and cluster of differentiation (CD)86 in liver tissue. Endostar also exhibited more marked downregulation of the levels of vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)‑2, MMP‑9 and interleukin‑17 during day 3‑9 treatment, resulting in short‑term normalization of tumor blood vessels. The period of vascular normalization was 3‑9 days. The results of the present study demonstrated that Endostar was able to induce the period of vascular normalization, contributing to a more efficacious means of HCC treatment combined with other chemotherapy, and this effect was associated with the immune response. It may be concluded that Endostar inhibited immunity‑associated angiogenesis behaviors of vascular endothelial cells in response to HCC. The results of the present study provided more reasonable possibility for the combination therapy of Endostar for the treatment of HCC. [ABSTRACT FROM AUTHOR]

The migration and invasion characteristics that are related to inflammatory response play important roles in the development of lung cancer. Astagaloside IV (AS-IV), an effective saponin component isolated from Astragali Radix, has been reported to inhibit metastasis of tumor cells. However, little is known about the underlying mechanism of AS-IV on inhibiting the migration and invasion characteristics of lung cancer cells. In the present study, cell proliferation was assessed by MTT colorimetric assay. Wound-healing assay and transwell chambers assay were used to detect the effects of AS-IV on the migration capacity and invasiveness of A549 cells. Metastasis-related bio-markers expressions were detected by Western blot analysis. Levels of inflammatory factors including transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cell supernatant were tested by enzyme linked immunosorbent assay (ELISA). The expressions of PKC-α, ERK1/2 and NF- κ B were analyzed by Western blot analysis. The results showed that the migration and invasion ability of A549 has been suppressed in presence of AS-IV. The levels of MMP-2, MMP-9 and integrin β1 were decreased significantly, whereas E-cadherin was increased by the treatment of different concentrations AS-IV. Furthermore, AS-IV also significantly decreased TGF-β1, TNF-α and IL-6 levels. Interestingly, PKC pathway inhibitor AEB071 (Sotrastaurin) (0.1 μM) or ERK inhibitor U0126 (1 μM) or NF- κ B inhibitor PDTC (1 μM) could affect suppression of AS-IV on cell invasion, at least partially. Our results suggested that the migration and invasion of AS-IV in A549 cells might be related to the PKC-α-ERK1/2-NF- κ B pathway. The result indicated that AS-IV could be used as a candidate for the inhibition of metastasis of human lung cancer. [ABSTRACT FROM AUTHOR]

Cytosine methylation is a well recognized epigenetic mark. Here, the methylation status of a salinity-tolerant wheat cultivar (cv. SR3, derived from a somatic hybridization event) and its progenitor parent (cv. JN177) was explored both globally and within a set of 24 genes responsive to salinity stress. A further comparison was made between DNA extracted from plants grown under control conditions and when challenged by salinity stress. The SR3 and JN177 genomes differed with respect to their global methylation level, and methylation levels were reduced by exposure to salinity stress. We found the genetic stress- (triggered by a combination of different genomes in somatic hybridization) induced methylation pattern of 13 loci in non-stressed SR3; the same 13 loci were found to undergo methylation in salinity-stressed JN177. For the salinity-responsive genes, SR3 and JN177 also showed different methylation modifications. C methylation polymorphisms induced by salinity stress were present in both the promoter and coding regions of some of the 24 selected genes, but only the former were associated with changes in transcript abundance. The expression of both TaFLS1 (encoding a flavonol synthase) and TaWRSI5 (encoding a Bowman–Birk-type protease inhibitor), which showed both a different expression and a different DNA methylation level between SR3 and JN177, enhanced the salinity tolerance of Arabidopsis thaliana. C methylation changes appear to be a common component of the plant response to stress, and methylation changes triggered by somatic hybridization may contribute to the superior salinity tolerance of SR3. [ABSTRACT FROM PUBLISHER]

Renal cell carcinoma (RCC) has always been considered resistant to chemotherapy. IR-780 is a near-infrared fluorescent (NIRF) dye that can be efficiently taken up by RCC cells. Cabazitaxel is a cytotoxic drug that interferes with mitosis by acting on tubulin. We chemically fused IR-780 and cabazitaxel into a new drug, Caba-780, which is expected to increase the sensitivity of RCC to chemotherapy. Infrared spectrum, nuclear magnetic resonance spectra, high-resolution mass spectra, and IR spectra were used for detecting structural characterization of the new synthetic drug Caba-780. The RCC cells lines ACHN and 786-O, as well as the non-cancerous human embryonic kidney cell line HEK293, were used to assess the cytotoxicity and tumor-efficient uptake of Caba-780 in vitro. The xenograft tumor-bearing mice and C57 mice were used to estimate the tumor-efficient imaging of Caba-780 as well as the safety and efficacy of its anti-tumor effects in vivo. The new synthetic drug Caba-780 retains the NIRF properties of IR-780. In vitro , Caba-780 was efficiently absorbed by the RCC cell lines ACHN and 786-O, and had an inhibitory effect on their growth, clonogenicity migration, and invasion. At the same time, Caba-780 retained the anti-tumor effect of cabazitaxel, which can inhibit the growth of tumor cells and promote apoptosis by inhibiting mitosis. In vivo experiments showed that Caba-780 can be taken up and imaged in tumor tissue, whereby it inhibits tumor growth. The novel fused molecule Caba-780 has application prospects in the diagnosis and treatment of RCC and makes RCC chemotherapy possible. [ABSTRACT FROM AUTHOR]