Comparison of novel flexible and traditional ureteral access sheath in retrograde intrarenal surgery.

OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.

MolLoG: A Molecular Level Interpretability Model Bridging Local to Global for Predicting Drug Target Interactions.

Developing new pharmaceuticals is a costly and time-consuming endeavor fraught with significant safety risks. A critical aspect of drug research and disease therapy is discerning the existence of interactions between drugs and proteins. The evolution of deep learning (DL) in computer science has been remarkably aided in this regard in recent years. Yet, two challenges remain: (i) balancing the extraction of profound, local cohesive characteristics while warding off gradient disappearance and (ii) globally representing and understanding the interactions between the drug and target local attributes, which is vital for delivering molecular level insights indispensable to drug development. In response to these challenges, we propose a DL network structure, MolLoG, primarily comprising two modules: local feature encoders (LFE) and global interactive learning (GIL). Within the LFE module, graph convolution networks and leap blocks capture the local features of drug and protein molecules, respectively. The GIL module enables the efficient amalgamation of feature information, facilitating the global learning of feature structural semantics and procuring multihead attention weights for abstract features stemming from two modalities, providing biologically pertinent explanations for black-box results. Finally, predictive outcomes are achieved by decoding the unified representation via a multilayer perceptron. Our experimental analysis reveals that MolLoG outperforms several cutting-edge baselines across four data sets, delivering superior overall performance and providing satisfactory results when elucidating various facets of drug-target interaction predictions.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

Diversity of purposes of use, time spent online, and depression among older Chinese Internet users.

Objectives: Previous studies on the associations between Internet use and older people's depression have mostly focused on single types of online activities, especially online social engagement. The current study investigated the diversity of purposes of Internet use and its interaction with the time spent online in shaping older Chinese Internet users' depression.Method: A sample of 974 Internet users aged 60 and above was adopted from the 2020 China Family Panel Studies wave. We adopted a latent class analysis (LCA) to explore the diverse purposes of internet usage.Results: The participants were classified into three distinct types: socializers, basic users, and maximizers. Basic users and maximizers use the Internet for various purposes, despite different intensities; socializers use the Internet only to keep connected with families and friends. Compared with basic users and maximizers, a longer time spent online among socializers was significantly associated with a higher level of depression.Conclusion: This study calls for a closer examination of online profiles among older Internet users; more attention should be paid to the potential harms of excessive Internet use for social reasons only among older adults. Practitioners should enhance older Internet users' digital literacy to maximize the wide-range benefits of Internet use and reduce potential health inequality.

Flexible ureteroscopy with novel flexible ureteral access sheath versus mini-percutaneous nephrolithotomy for treatment of 2-3 cm renal stones.

OBJECTIVES: To assess and compare the effectiveness and safety of flexible ureteroscopy (f-URS) with a novel flexible ureteral access sheath (f-UAS) versus mini-percutaneous nephrolithotripsy (mini-PCNL) in treating 2-3 cm renal stones. METHODS: Retrospectively analyzed consecutive cases that underwent f-URS with f-UAS (12/14 Fr) from January 29, 2022, to November 30, 2022. Consecutive cases that underwent mini-PCNL (18 Fr) from June 5, 2021, to January 26, 2022, were selected as controls. The f-UAS is a novel device with a 10 cm anterior tip that passively bends along with the f-URS to enter the renal calyx. We analyzed demographic characteristics, stone parameters, operative time, stone-free rates (SFR), hospitalization time, and complication. RESULTS: A total of 96 consecutive cases that underwent f-URS with f-UAS and 96 consecutive cases that underwent mini-PCNL were included in the study. There were no significant differences between the two groups in terms of operative time (p = 0.06), stone volume clearance (p = 0.533) and complete SFR (p = 0.266) on the first postoperative day or residual Stone after 1 month (p = 0.407). We observed a significantly shorter postoperative hospital stay (1.4 days vs. 2.1 days; p < 0.001) and a lower decrease in hemoglobin levels (0.39 g/dL vs. 0.68 g/dL; p < 0.001) in the f-UAS group. The mini-PCNL group had a significantly higher overall complication rate (13.5%) compared with the f-UAS group (5.2%; p = 0.048). CONCLUSIONS: In the treatment of 2-3 cm renal stones, f-URS with a novel f-UAS may provide a superior alternative to mini-PCNL, potentially challenging its established status.

Novel cuproptosis-related long non-coding RNA signature to predict prognosis in prostate carcinoma.

BACKGROUND: Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function. METHODS: RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships. RESULTS: The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed. CONCLUSIONS: A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.

Influence of samarium modification on the phase-change performance and phase structure of tin antimonide.

This work presents the optimization of the crystallization behavior and reliability of Sn15Sb85thin films by doping Sm element. The phase transition behaviors induced by thermal were investigated byin situresistance measurement. With the addition of Sm element, Sn15Sb85film exhibits the superior crystallization temperature (232 °C) and data conservation (172.32 °C for 10 years), larger activation energy of crystallization (4.91 eV) and crystalline resistance (∼103Ω), which contributes to the increased thermal stability of the amorphous state and decrease in the programming energy. The Sm-doping can broaden the energy band gap from 0.55 to 1.07 eV. The amorphous Sm and Sn compositions could retard grain growth and refine grain size from 21.13 to 11.13 nm, combining with x-ray diffraction and x-ray photoelectron spectroscopy. The surface morphology of Sn15Sb85film becomes smoother after Sm doping as determined by atomic force microscopy images, resulting in the improved interfacial reliability. Phase change memory devices based on Sm0.095(Sn15Sb85)0.905films can successfully achieve the complete SET and RESET reversible operation process with high operating speed (200 ns) and low power consumption (1.6 × 10-10J). The results suggest that doping the proper concentration of Sm element will be an effectual solution to adapt and optimize the crystallization properties of Sn15Sb85phase change material.

Simultaneously achieving high performance of thermal stability and power consumption via doping yttrium in Sn15Sb85thin film.

The effects of yttrium dopants on the phase change behavior and microstructure of Sn15Sb85films have been systematically investigated. The yttrium-doped Sn15Sb85film has the higher phase transition temperature, ten year data retention ability and crystallization activation energy, which represent a great improvement in thermal stability and data retention. X-ray diffraction, transmission electron microscopy and x-ray photoelectron spectroscopy reveal that the amorphous Sn and Y components restrict the grain growth and decrease the grain size. Raman mode typically associated with Sb is altered when the substance crystallized. Atomic force microscopy results show that the surface morphology of the doped films becomes smoother. T-shaped phase change storage cells based on yttrium-doped Sn15Sb85films exhibit the lower power consumption. The results demonstrate that the crystallization characteristics of Sn15Sb85film can be tuned and optimized through the yttrium dopant for the excellent performances of phase change memory.

Associations between parents' and grandparents' depressive symptoms, intergenerational coparenting relationships, and (grand)parenting behaviors: An actor-partner interdependence mediation model.

Intergenerational coparenting has become an increasingly common family phenomenon across the globe. In this study, we examined the associations among depressive symptoms, perceptions of intergenerational coparenting relationships, and (grand)parenting behaviors. Participants were parents and grandparents most involved in child care from 464 Chinese coparenting families sampled in urban China. The results from a test of the actor-partner interdependence mediation model showed that the depressive symptoms of parents and grandparents were indirectly and positively related to their harsh discipline of children or negatively related to their supportiveness toward children, and the association was mediated via their own perceptions of the coparenting relationship. In addition, parents' depressive symptoms were indirectly and positively related to grandparental harsh parenting or negatively related to grandparental supportive parenting through grandparents' perceived coparenting relationship. Grandparents' depressive symptoms were indirectly and positively related to parental harsh parenting or negatively related to parental supportive parenting through parents' perceptions of the coparenting relationship. This study highlights the importance of uncovering the processes and dynamics of parent-grandparent coparenting practices through a lens of family systems and interdependence theories as well as a dyadic approach. It also has practical implications for family interventions in the context of intergenerational coparenting. Specifically, this study recommends parallel (grand)parenting intervention sessions for parents and grandparents simultaneously to benefit the well-being of all three generations.

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer.

BACKGROUND: MAPK8IP2 is one of the JNK-interacting proteins (JIPs) family members, and is involved in the regulation of the JNK and P38 MAPK signaling pathways. MAPK8IP2 has been reported to be closely associated with several cancers. However, the biological function of MAPK8IP2 in prostate cancer (PCa) remains unclear. METHODS: MAPK8IP2 expression in PCa and subgroups of PCa was analyzed by public databases. The prognostic role of MAPK8IP2 in prostate cancer was analyzed using the Cox regression method. The potential mechanism by which MAPK8IP2 affects PCa progression was investigated by utilizing public data, including genetic alteration, DNA methylation, m6A methylation, and immune infiltration data. We further performed in vitro assays to validate the effect of MAPK8IP2 on PCa cell proliferation, migration and invasion. RESULTS: MAPK8IP2 is highly expressed in PCa tissues. Overexpression of MAPK8IP2 is associated with adverse clinicopathological factors and a poor prognosis in PCa. Receiver operating curve analysis showed that MAPK8IP2 can distinguish PCa tissues from non-PCa tissues with a certain accuracy (AUC = 0.814). The MAPK8IP2 genetic alteration rate was 2.6% and MAPK8IP2 alterations correlated with a poor prognosis. We also found that CDK12 and TP53 mutations were associated with MAPK8IP2 expression. The DNA methylation level of MAPK8IP2 was higher in primary tumors than in normal tissues, and the high MAPK8IP2 DNA methylation group of PCa patients had poor survival. Enrichment analysis indicated that MAPK8IP2 was involved in the MAPK signaling pathway. In vitro, knockdown of MAPK8IP2 inhibited PCa cell proliferation, migration and invasion. CONCLUSION: MAPK8IP2 is a potential target for PCa treatment and can serve as a novel biomarker for PCa diagnosis and prognosis evaluation.

How does tea (Camellia sinensis) produce specialized metabolites which determine its unique quality and function: a review.

Tea (Camellia sinensis) is both a plant and a foodstuff. Many bioactive compounds, which are present in the final tea product and related to its quality or functional properties, are produced during the tea manufacturing process. However, the characteristic secondary metabolites, which give tea its unique qualities and are beneficial to human health, are produced mainly in the leaves during the process of plant growth. Therefore, it is important to understand how tea leaves produce these specialized metabolites. In this review, we first compare the common metabolites and specialized metabolites in tea, coffee, cocoa, and grape and discuss the occurrence of characteristic secondary metabolites in tea. Progress in research into the formation of these characteristic secondary metabolites in tea is summarized, including establishing a biological database and genetic transformation system, and the biosynthesis of characteristic secondary metabolites. Finally, speculation on future research into the characteristic secondary metabolites of tea is provided from the viewpoints of the origin, resources, cultivation, and processing of tea. This review provides an important reference for future research on the specialized metabolites of tea in terms of its characteristics.

CT-Based Predictor for the Success of 12/14-Fr Ureteral Access Sheath Placement.

Purpose: Ureteral access sheaths (UAS) are widely used in retrograde intrarenal surgery (RIRS), and this study aimed to develop a model for predicting the success of UAS placement based on computed tomography. Methods: We analyzed the clinical data of 847 patients who received ureteroscopy. Data on patient and stone characteristics and several computed tomography (CT)-based measurements were collected. A nomogram predicting the success of UAS placement was developed and validated using R software. Results: Two hundred and forty-seven patients were identified. Twenty-five patients (10.1%) failed to pass through the UAS. A model with three factors including the short diameter of ureteral calculi, the short diameter of hydronephrosis, and the diameter of the narrowest part of the renal parenchyma was to be strongly practical and had a high area under the curve on internal validation (80.3%). Using a threshold cutoff of 92%, the sensitivity and specificity for predicting UAS placement were 0.35 and 0.92, respectively. Conclusion: Our study provides a nomogram for predicting the success of UAS placement, and this model could help discriminate patients who are likely to suffer from failed UAS insertion; preoperative ureteral stenting is recommended according to the prediction.

Identification of the Risk Factors for the Failure of Ureteral Access Sheath Placement.

Purpose: Insertion of a ureteral access sheath (UAS) may fail in some patients in retrograde intrarenal surgery (RIRS), and this study aimed to seek preoperative risk factors for the failure of 12/14F UAS placement. Methods: We retrospectively analyzed 260 consecutive patients who underwent RIRS between May 2020 and March 2022 at our institution. Data on patient and stone characteristics and several computed tomography (CT)-based measurements were collected and compared between the success and failure UAS placement groups. Results: Twenty-nine (11.2%) patients failed to insert the UAS. Age, gender, height, weight, stone side, stone location, length of history, and computed tomography (CT)-based parameters were not significant differences between the two groups. Univariate logistic regression analyses showed sex (female/male) (odds ratio: 0.287 and 95% CI [0.107, 0.722], p=0.013), length of history 15-31 days (odds ratio: 0.315 and 95% CI [0.102, 0.974], p=0.045), length of history >31 days (odds ratio: 0.202 and 95% CI [0.051, 0.805], p=0.023), and diameter of the ipsilateral common iliac artery (odds ratio: 1.285 and 95% CI [1.018, 1.623], p=0.035) were associated with UAS placement. Conclusion: Our study indicated that males, the short length of history, and the short diameter of the ipsilateral common iliac artery were the risk factors for the failure of UAS placement.

Preoperative aspartate transaminase/alanine transaminase ratio as a prognostic biomarker in primary non-muscle-invasive bladder cancer: a propensity score-matched study.

PURPOSE: To evaluate the prognostic value of the aspartate transaminase/alanine transaminase (AST/ALT) ratio in primary non-muscle-invasive bladder cancer (NMIBC) using propensity score matching (PSM) analysis. METHODS: We retrospectively collected the clinical and pathological data from 314 patients with primary NMIBC who underwent transurethral resection of bladder tumor. The full cohorts were divided into a low AST/ALT ratio group and a high AST/ALT ratio group according to the optimal cut-off value which was obtained based on the analysis of the receiver operating characteristic curve for the 3-year recurrence-free survival (RFS). After 1:1 PSM, the correlation between preoperative AST/ALT ratio and survival prognosis was evaluated by Kaplan-Meier analysis with log-rank tests. The independent prognostic factors for RFS and progression-free survival (PFS) were also analyzed. RESULTS: The optimum cutoff value of the preoperative AST/ALT ratio was 1.40. Before PSM, a high AST/ALT ratio was correlated with the larger proportion of age > 60 years (P = 0.007) and the worse pathological T stage (P < 0.001). After PSM, patients with a high AST/ALT ratio had poorer RFS and PFS than patients with a low AST/ALT ratio (all P < 0.001). In addition, multivariate Cox regression analysis indicated that preoperative AST/ALT ratio was considered as an independent prognostic factor of RFS (HR 2.865; 95%CI 1.873-4.381; P < 0.001) and PFS (HR 4.771; 95%CI 2.607-8.734; P < 0.001) in patients with primary NMIBC. CONCLUSIONS: The high AST/ALT ratio group tended to have poorer RFS and PFS than the low AST/ALT ratio group. Our results also indicated that the elevated preoperative AST/ALT ratio could be seen as a useful prognostic biomarker for predicting early disease recurrence and progression in patients with primary NMIBC.

Within-family patterns of intergenerational emotional closeness and psychological well-being of older parents in China.

Objectives: There may be a substantial difference in the intergenerational emotional closeness among offspring in a multi-child family, both regarding the overall level as well as the extent to which older parents differentiate emotional closeness between their children. This study addressed different within-family patterns based on the average level and differentiation of older parent-child emotional closeness. It also examined the associations between these distinct patterns and the psychological well-being of older parents in China.Method: We derived a final sample of 4247 older parents (aged 60+) with 14,461 children from the baseline wave (2010) of the China Family Panel Studies. A latent profile analysis was applied to classify within-family patterns based on two indicators: within-family mean level and differentiation of parent-child emotional closeness among offspring. Ordered logistic regression and ordinary least square (OLS) regression were used to investigate the associations between these patterns and older adults' life satisfaction and depression, respectively.Results: Two family patterns of parent-child emotional closeness were identified: tight-knit (91.50%) and highly ambivalent (8.50%). Compared with the former, older parents having highly ambivalent relationships across multiple offspring tended to have lower life satisfaction and higher levels of depression.Conclusion: This study highlighted the importance of capturing different within-family dynamics of intergenerational emotional closeness in Chinese families. It also pointed out the negative effects of collective ambivalence for older adults' psychological well-being.

Histone tales: lysine methylation, a protagonist in Arabidopsis development.

Histone methylation plays a fundamental role in the epigenetic regulation of gene expression driven by developmental and environmental cues in plants, including Arabidopsis. Histone methyltransferases and demethylases act as 'writers' and 'erasers' of methylation at lysine and/or arginine residues of core histones, respectively. A third group of proteins, the 'readers', recognize and interpret the methylation marks. Emerging evidence confirms the crucial roles of histone methylation in multiple biological processes throughout the plant life cycle. In this review, we summarize the regulatory mechanisms of lysine methylation, especially at histone H3 tails, and focus on the recent advances regarding the roles of lysine methylation in Arabidopsis development, from seed performance to reproductive development, and in callus formation.

Transvesical robot-assisted radical prostatectomy: initial experience and surgical outcomes.

OBJECTIVES: To describe in detail the techniques for transvesical robot-assisted radical prostatectomy (RARP) using the da Vinci Si/Xi system (Intuitive Surgical, Sunnyvale, CA, USA) and to evaluate functional and oncological outcomes in 35 patients with prostate cancer. PATIENTS AND METHODS: Thirty-five patients with localized prostate cancer were enrolled for transvesical RARP. The patients' preoperative data (mean ± sd age 63.4 ± 8.1 years, body mass index 28.6 ± 5.3 kg/m2 , total prostate-specific antigen 10.8 ± 4.9 ng/mL and prostate volume 30.6 ± 14.4 mL, and median [interquartile range {IQR}] biopsy Gleason score 6 [6-7], and International Index of Erectile Function [IIEF]-5 score 18 [16-20]) were collected. Preoperative assessment revealed 28 cases of cT2a and seven cases of cT2b disease. All patients were continent preoperatively (defined as no pad required or one dry pad per day as a precaution). Surgical results and peri-operative complications were assessed. All patients were followed up for at least 12 months postoperatively. RESULTS: The mean operating time was 150 ± 35 min. Estimated blood loss was 100 ± 45 mL. Urinary infection was noted in one patient and managed with levofloxacin. Another patient complained of nocturia on postoperative day 14, which was relieved with solifenacin succinate. Urethral catheters were removed on postoperative day 7. Thirty-two patients achieved immediate urinary continence, with three patients returning to full continence on postoperative day 14. Postoperative pathology confirmed 24 pT2a cases, nine pT2b cases and two pT2c cases (median [IQR] Gleason score 6 [6-7]). Positive surgical margins were found in four patients (11.4%). No urethral stricture or urinary leakage was noted on urethrocystography taken 3 months after surgery. Urodynamic studies were performed preoperatively and 6 months after surgery: median (IQR) maximum urinary flow 12.2 (10.2-14.9) vs 13.7 (10.1-15.0) mL/s; bladder capacity 385.3 (351.3-410.2) vs 370.2 (330.1-395.4) mL; and voiding phase detrusor contractility 38.5 (27.8-42.3) vs 35.6 (28.3-41.3) mmH2 O, respectively. During a minimum of 12 months of follow-up, no biochemical recurrence was noted in any patient. The median (IQR) IIEF-5 score was 17 (16-19). CONCLUSIONS: The transvesical approach is a valid alternative to RARP in selected patients, providing promising postoperative urinary continence. Long-term functional and oncological results require further investigation.

Metabolism of Gallic Acid and Its Distributions in Tea (Camellia sinensis) Plants at the Tissue and Subcellular Levels.

In tea (Camellia sinensis) plants, polyphenols are the representative metabolites and play important roles during their growth. Among tea polyphenols, catechins are extensively studied, while very little attention has been paid to other polyphenols such as gallic acid (GA) that occur in tea leaves with relatively high content. In this study, GA was able to be transformed into methyl gallate (MG), suggesting that GA is not only a precursor of catechins, but also can be transformed into other metabolites in tea plants. GA content in tea leaves was higher than MG content-regardless of the cultivar, plucking month or leaf position. These two metabolites occurred with higher amounts in tender leaves. Using nonaqueous fractionation techniques, it was found that GA and MG were abundantly accumulated in peroxisome. In addition, GA and MG were found to have strong antifungal activity against two main tea plant diseases, Colletotrichum camelliae and Pseudopestalotiopsis camelliae-sinensis. The information will advance our understanding on formation and biologic functions of polyphenols in tea plants and also provide a good reference for studying in vivo occurrence of specialized metabolites in economic plants.

Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo.

MLN4924, also known as pevonedistat, is the first-in-class inhibitor of NEDD8-activating enzyme, which blocks the entire neddylation modification of proteins. Previous preclinical studies and current clinical trials have been exclusively focused on its anticancer property. Unexpectedly, we show here, to our knowledge for the first time, that MLN4924, when applied at nanomolar concentrations, significantly stimulates in vitro tumor sphere formation and in vivo tumorigenesis and differentiation of human cancer cells and mouse embryonic stem cells. These stimulatory effects are attributable to (i) c-MYC accumulation via blocking its degradation and (ii) continued activation of EGFR (epidermal growth factor receptor) and its downstream pathways, including PI3K/AKT/mammalian target of rapamycin and RAS/RAF/MEK/ERK, via inducing EGFR dimerization. Finally, MLN4924 accelerates EGF-mediated skin wound healing in mouse and stimulates cell migration in an in vitro culture setting. Taking these data together, our study reveals that neddylation modification could regulate stem cell proliferation and differentiation and that a low dose of MLN4924 might have a therapeutic value for stem cell therapy and tissue regeneration.

Characterization and subcellular localization of histone deacetylases and their roles in response to abiotic stresses in soybean.

BACKGROUND: Histone deacetylases (HDACs) function as key epigenetic factors in repressing the expression of genes in multiple aspects of plant growth, development and plant response to abiotic or biotic stresses. To date, the molecular function of HDACs is well described in Arabidopsis thaliana, but no systematic analysis of this gene family in soybean (Glycine max) has been reported. RESULTS: In this study, 28 HDAC genes from soybean genome were identified, which were asymmetrically distributed on 12 chromosomes. Phylogenetic analysis demonstrated that GmHDACs fall into three major groups previously named RPD3/HDA1, SIR2, and HD2. Subcellular localization analysis revealed that YFP-tagged GmSRT4, GmHDT2 and GmHDT4 were predominantly localized in the nucleus, whereas GmHDA6, GmHDA13, GmHDA14 and GmHDA16 were found in both the cytoplasm and nucleus. Real-time quantitative PCR showed that GmHDA6, GmHDA13, GmHDA14, GmHDA16 and GmHDT4 were broadly expressed across plant tissues, while GmHDA8, GmSRT2, GmSRT4 and GmHDT2 showed differential expression across various tissues. Interestingly, we measured differential changes in GmHDACs transcripts accumulation in response to several abiotic cues, indicating that these epigenetic modifiers could potentially be part of a dynamic transcriptional response to stress in soybean. Finally, we show that the levels of histone marks previously reported to be associated with plant HDACs are modulated by cold and heat in this legume. CONCLUSION: We have identified and classified 28 HDAC genes in soybean. Our data provides insights into the evolution of the HDAC gene family and further support the hypothesis that these genes are important for the plant responses to environmental stress.