BACKGROUND:Hickory (Carya cathayensis) nuts, renowned for their health benefits and delightful taste, contain abundant bioactive compounds, particularly polyphenols. However, the specific mechanisms underlying their antioxidant properties and anti-aging effects remain elusive. PURPOSE:This study aims to investigate the effects of hickory nut polyphenols (HNP) on oxidative stress mitigation and aging modulation. METHODS:The innovative integration of medium-pressure liquid chromatography (MPLC) with in vitro bioactive screening was employed to discover an optimized HNP fraction (HNP3-2). Anti-aging effects of HNP3-2 on Caenorhabditis elegans (C. elegans) were determined through lifespan analysis, lipofuscin accumulation quantification, and motility assessments. Oxidative stress resistance was further evaluated by detecting the reactive oxygen species (ROS) contents, lipid peroxidation, and antioxidase activities. Integrative approaches combining transcriptomic, qRT-PCR, GFP reporter strains, and gene knockout mutants were utilized to explore the potential regulatory mechanisms. Non-targeted metabolomics was employed to conduct a comprehensive profiling analysis of HNP and their bioactive fractions. RESULTS:HNP3-2 significantly decreased ROS production, lipofuscin accumulation, and lipid peroxidation, while enhanced the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). It also conferred robust protection against oxidative stress induced by H2O2 and juglone. HNP3-2 regulated lifespan extension mainly via the DAF-16/-2 insulin/IGF-1 signaling (IIS), which was further validated using loss- and gain-of-function mutants including age-1, akt-1/2, daf-2, and daf-16, as well as worms overexpressing SOD-3, GST-4, and DAF-16. Metabolomic analysis identified 31 kinds of polyphenol compounds displaying abundance patterns congruent with the overall antioxidant potency in vitro. CONCLUSION:This study first reveals the efficacy of HNP as a promising antioxidant and anti-aging intervention. Notably, the screened bioactive fraction HNP3-2 acts primarily by modulating the DAF-16/DAF-2 insulin/IGF-1 signaling cascade, operating through a mechanism independent of dietary restriction. Collectively, these findings position HNP as a breakthrough candidate for next-generation gerotherapeutics, with translational potential for advancing human aging research.

Background: The apoptosis affected the prostate adenocarcinoma (PRAD); we aimed to explore the potential pathogenesis of high-risk patients based on the apoptosis features. Method: The RNA-seq data of patients and apoptosis genes were used for apoptosis score calculation via "GSVA" package; then, the weighted gene coexpression network analysis (WGCNA) and Lasso algorithm were performed for a RiskScore model. After that, the "maftools" package was applied for the somatic mutation analysis. By combining the Kaplan-Meier (KM) survival curves in order to compare the prognosis of different subgroups of patients, Cell Counting Kit-8 (CCK-8), EdU staining, and Transwell assays were performed. Protein expression was measured using western blotting. Finally, the activity of PRAD cells in macrophage polarization was detected using coculture and immunofluorescence assays. Results: The PRAD samples had significantly lower apoptosis scores, and the RiskScore supported the risk stratification of patients. In somatic mutation analysis, EPHB1 and KIF13A from the top six mutant genes were overexpressed in 22RV1 and PC-3 tumor cells, and low levels of EPHB1 indicated a better prognosis. Overexpression or knockdown of EPHB1 affected cell viability, proliferation, and invasion. We found that high expression of EPHB1 interacting with GSK3B protein promoted the expression of p-SMAD3 in 22RV1 cells with high levels of antiapoptotic and invasion markers (BCL2, Snail, and N-CAD). Importantly, GSK3B and EPHB1 knockdown inhibited p-SMAD3 activation and promoted proapoptotic features, accompanied by a reduction in macrophage M2 polarization. Conclusion: This study revealed that EPHB1 plays a pivotal role in activating the EPHB1-GSK3B-SMAD3 pathway to facilitate PRAD progression.

Hyperoside is a natural flavonol glycoside widely found in plants and has been reported to have a variety of pharmacological effects, including anticancer abilities. In this study, we demonstrated for the first time that hyperoside inhibited the proliferation of bladder cancer cells in vitro and in vivo. Moreover, hyperoside could not only induce cell cycle arrest, but also induce apoptosis of a few bladder cancer cells. Quantitative proteomics, bioinformatics analysis and Western blotting confirmed that hyperoside induced the overexpression of EGFR, Ras and Fas proteins, which affects a variety of synergistic and antagonistic downstream signaling pathways, including MAPKs and Akt, ultimately contributing to its anticancer effects in bladder cancer cells. This study reveals that hyperoside could be a promising therapeutic strategy for the prevention of bladder cancer.

4-Hydroxyphenylacetate-3-hydroxylase (4HPA3H; EC 1.14.14.9) is a heterodimeric flavin-dependent monooxygenase complex that catalyzes the ortho-hydroxylation of resveratrol to produce piceatannol. Piceatannol has various health benefits and valuable applications in food, medicine, and cosmetics. Enhancing the catalytic activity of 4HPA3H toward resveratrol has the potential to benefit piceatannol production. In this study, the critical amino acid residues in the substrate pocket of 4HPA3H that affect its activity toward resveratrol were identified using semi-rational engineering. Two key amino acid sites (I157 and A211) were discovered and the simultaneous "best" mutant I157L/A211D enabled catalytic efficiency (Kcat/Km-resveratrol) to increase by a factor of 4.7-fold. Molecular dynamics simulations indicated that the increased flexibility of the 4HPA3H substrate pocket has the potential to improve the catalytic activity of the enzyme toward resveratrol. On this basis, we produced 3.78 mM piceatannol by using the mutant I157L/A211D whole cells. In this study, we successfully developed a highly active 4HPA3H variant for the hydroxylation of resveratrol to piceatannol.

Catechols have important applications in the pharmaceutical, food, cosmetic, and functional material industries. 4-hydroxyphenylacetate-3-hydroxylase (4HPA3H), a two-component enzyme system comprising HpaB (monooxygenase) and HpaC (FAD oxidoreductase), demonstrates significant potential for catechol production because it can be easily expressed, is highly active, and exhibits ortho-hydroxylation activity toward a broad spectrum of phenol substrates. HpaB determines the ortho-hydroxylation efficiency and substrate spectrum of the enzyme; therefore, studying its structure–activity relationship, improving its properties, and developing a robust HpaB-conducting system are of significance and value; indeed, considerable efforts have been made in these areas in recent decades. Here, we review the classification, molecular structure, catalytic mechanism, primary efforts in protein engineering, and industrial applications of HpaB in catechol synthesis. Current trends in the further investigation of HpaB are also discussed.

The toxicity of high-chlorinated polychlorinated biphenyls (PCBs) can be efficiently reduced through anaerobic dechlorination. However, this approach suffers a lot in face of in situ microbial remediations, like a shortage of biomass. In this study, we showed that the amendment of organic matters could help microbiota in paddy soil with anaerobic dechlorination and greatly shortened the lag period. The presence of organic matters offered a better environment for dechlorinating bacteria. They provided not only a more strictly anaerobic milieu but also copious carbon sources. By using high-throughput 16S rRNA gene sequencing, genera Dehalobacter, Dehalobacterium, and Desulfitobacterium capable of dechlorination were identified in enriched cultures. Taken together, this study proved that extra organic matters can promote anaerobic dechlorination in paddy soil slurry microcosm systems, which provides new insights into the bioremediation of PCB-contaminated soils.

通过投加颗粒活性炭(GAC)强化直接种间电子传递(DIET),进而提升餐厨垃圾中常见食用油的厌氧消化产甲烷效能,并分析投加GAC对微生物群落结构的影响.研究发现,与未投加GAC的对照组相比较,投加GAC的实验组可以高效稳定地进行厌氧消化产甲烷.在菜籽油厌氧消化过程中,对照组的乙酸浓度在第7天达到最大值(7 mmol/L),之后基本保持不变.而在投加GAC的实验组中,乙酸浓度在第7天达到最大值(3.9 mmol/L),之后逐渐降低,到第13天基本为0.与此同时,实验组的最大甲烷产量约为对照组的3.5倍.因而,投加GAC促进了乙酸的降解和甲烷的转化.对微生物群落结构进行分析发现,投加GAC的实验组中富集了大量可能具有胞外电子传递功能的细菌(Syntrophomonas和Geobacter),以及可以参与DIET的产甲烷菌(Methanosarcina),表明投加GAC可以有效富集以上三种微生物,并通过GAC作为电子载体促进菜籽油厌氧反应体系中DIET的形成,进而促进菜籽油的降解,提高甲烷产量.

Small double-stranded RNAs (dsRNAs) have been proved to effectively up-regulate the expression of particular genes by targeting their promoters. These small dsRNAs were also termed small activating RNAs (saRNAs). We previously reported that several small double-stranded RNAs (dsRNAs) targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can up-regulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in bladder cancer. Promisingly, we found that up-regulation of PAWR by saRNA inhibited the growth of bladder cancer cells by inducing cell apoptosis and cell cycle arrest which was related to inhibition of anti‑apoptotic protein Bcl-2 and inactivation of the NF-κB and Akt pathways. The activation of the caspase cascade and the regulation of cell cycle related proteins also supported the efficacy of the treatment. Moreover, our study also showed that these saRNAs cooperated with cisplatin in the inhibition of bladder cancer cells. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for bladder cancer.

Apocynum venetum L. and Eleutherococcus senticosus have been used for hundreds of years to treat hypertension in China. In previous research, there was not a suitable quality control of method for the formulas of Apocynum venetum L. and Eleutherococcus senticosus. It is urgent and essential to develop modern analytical methods for Apocynum venetum L. and Eleutherococcus senticosus to ensure the quality of the formulas. A rapid approach for simultaneous determination of hyperoside, isoquercitrin and eleutheroside E in Apocynum venetum L. and Eleutherococcus senticosus by high-performance liquid chromatography with a diode array detector was described and validated. The full method validation, including the linearity, limits of detection and quantification, precision, repeatability, stability and recovery, was examined. All target components, including isomers of hyperoside and isoquercitrin, were baseline separated in 35 min. The developed method was sensitive, reliable and feasible. With this method, the optimal decoction conditions of Apocynum venetum L. and Eleutherococcus senticosus were selected, and their quality analysis was carried out. Furthermore, an herbal compatibility study of Apocynum venetum L. and Eleutherococcus senticosus based on detecting variations in the content of their active ingredients was performed by the developed HPLC method. It could be an alternative for the quantitative analysis of herbs that contain hyperoside, isoquercitrin or (and) eleutheroside E in the future.

Due to long-chain fatty acids (LCFAs) and acidification, rapeseed oil as a typical lipid in kitchen waste is difficult to be biodegraded by anaerobic digestion. It has been reported that incorporation of some conductive materials into reactors treating complex organic matter could enhance reactor performance. In this study, the aim was to study this possibility of application of granular activated carbon (GAC) in anaerobic digestion of rapeseed oil. As expected, the GAC-amended reactor could significantly improve methane yield and reduce acidification. Besides, the GAC-amended broth could efficiently degrade palmitate into methane. Microbial community analysis showed that bacteria (Syntrophomonas) and methanogens (Methanosarcina) were greatly enriched on the GAC surface in GAC-amended system. These results, and the kwon of easy enrichment of Syntrophomonas on conductive materials or current-harvesting electrodes in methanogenic and/or electrogenic systems, suggest that Syntrophomonas could participate in direct interspecies electron transfer with Methanosarcina species, when GAC is available as an electron transfer mediator. Hence, the addition of GAC could efficiently, stably and environmentally enhance the methanogenic metabolism of rapeseed oil.

ABSTRACT Emerging evidence has elucidated that microRNAs (miRNAs) transcribed from miRNA cluster at DLK‐DIO3 imprinted domain are involved in various cancers. However, as one member of this cluster, the underlying mechanisms and functions of miR‐381‐3p in bladder cancer (BCa) still remains elusive. Here we demonstrate that the hypermethylated status of upstream maternally expressed gene 3 divergent methylation region reduces the expression of miR‐381‐3p in BCa by bisulfite‐sequencing PCR. In vitro and in vivo experiments indicate that overexpression of miR‐381‐3p significantly inhibits cell proliferation via inducing G 1 phase arrest and migration via down‐regulating MET and CCNA2 induced EMT progression. CDK6/CCNA2/MET are all identified as the direct targets of miR‐381‐3p by bioinformatics analysis and dual‐luciferase reporter assay. Furthermore, inhibition of CCNA2 mediated by miR‐381‐3p as the crucial biregulator not only participates in the proliferation regulation with CDK6 in cell cycle but also modulates the EMT progression via ROCK/AKT/β‐catenin/SNAIL pathway, which establishes an EMT circuit combined with miR‐381‐3p/MET/AKT/GSK‐3β/SNAIL pathway, and SNAIL is the last confocal target to induce EMT progression. To conclude, we propose 2 novel regulatory circuits mediated by miR‐381‐3p in BCa, which may assist in the development of more effective therapies against BCa in the future.—Li, J., Ying, Y., Xie, H., Jin, K., Yan, H., Wang, S., Xu, M., Xu, X., Wang, X., Yang, K., Zheng, X., Xie, L. Dual regulatory role of CCNA2 in modulating CDK6 and MET‐mediated cell‐cycle pathway and EMT progression is blocked by miR‐381‐3p in bladder cancer. FASEB J. 33, 1374–1388 (2019). www.fasebj.org

Background Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population. Methods We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs). Random effects logistic regression was used to calculate odds ratios (ORs) of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling. Results Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (P-trend = 0.04) with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95% CI: 0.28-0.98). Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61), neither were vigorous (P-trend = 0.60) or moderate levels of physical activity (P-trend = 0.21). Walking and cycling were not significantly associated with either prostate (P-trend > = 0.62) or bladder cancer risk (P-trend > = 0.25). Conclusions The findings of this largest ever case-control study in China investigating the relationship between physical activity and prostate and bladder cancer suggest that overall physical activity is associated with a decreased risk of prostate cancer, but not with bladder cancer.

RNA activation (RNAa) is a promising discovery whereby expression of a particular gene can be induced by targeting its promoter using small double-stranded RNAs (dsRNAs) also termed small activating RNAs (saRNAs). We previously reported that several small dsRNAs targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can upregulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in prostate cancer cells. Promisingly, we found that upregulation of PAWR by saRNA inhibited the growth of prostate cancer cells by inducing cell apoptosis which was related to inactivation of the NF-κB and Akt pathways. The decreased anti‑apoptotic protein Bcl-2 and activation of the caspase cascade and poly(ADP-ribose) polymerase (PARP) also supported the efficacy of the treatment. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for prostate and other types of cancer.

The environmental pollution and health risks caused by the improper disposal of electric and electronic waste (e‐waste) have become urgent global issues. Severe and widespread contaminations of polychlorinated biphenyls (PCBs) are commonly found in drylands or paddy fields in Taizhou, a major hotspot of e‐waste recycling in China. In this research, comparative study was performed on PCBs transformation in polluted agricultural soil under drying and flooded conditions. Uncontaminated soils spiked with PCB31 (2,3,4′‐trichlorobiphenyl) and PCB153 (2,2′,4,4′,5,5′‐hexachlorobiphenyl) were also investigated to verify the transformation characteristics of highly and less chlorinated congeners under both conditions. In a 180‐day incubation period, total PCBs in contaminated soil decreased 63.85% in paddy conditions but only 33.10% in dryland conditions; dissipation rate of highly chlorinated congeners in flooded treatment was 39% higher than drying treatment. Furthermore, PCB153 spiked soil exhibited a 19% higher removal rate in flooded conditions than drying ones. In contrast, degradation rate of PCB31 under drying conditions was 33% higher. It was proposed that drying conditions in dryland or fallowed paddy field favoured the aerobic biodegradation of less chlorinated PCBs, whereas paddy conditions benefitted anaerobic reductive dechlorination process of highly chlorinated congeners, which was crucial for completely mineralization of PCBs.

Urethral leiomyoma is an extremely rare condition that arises from the smooth muscle of the urethra. To the best of our knowledge, there is only a single reported recurrence treated by a repeat excision in the literature to date. The present study reports an exceptionally rare case of a recurrent huge leiomyoma of the female urethra. The 47-year-old female was diagnosed with a huge mass located between the urethra and vagina during a gynecological examination. The patient had no symptoms and was successfully treated with transabdominal excision. Pathological examinations revealed a leiomyoma of the urethra. The patient was followed up for one year without any sign of recurrence.

Objective:To construct a PSA luciferase report plasmid and monitor the growth and metastasis of prostate cancer after emasculation in SCID mice.Methods:PSA promoter sequence and luciferase gene were amplified by PCR and subsequently inserted into pZsCreen1-1 vector to construct pPSA-FL-Luc vector.LNCaP cells that were stably transfected with pPSA-FL-Luc were used to establish a SCID mouse xenograft model.Then,the growth and metastasis of prostate cancer were monitored via living imaging.Results:We successfully constructed a PSA luciferase piasmid,pPSA-FL-Luc.DHT enhanced lucifcrase activity in a concentration-dependent manner in 293 T cells with pPSA-FL-Luc transfection.Prostate cancer SCID mouse model was established with pPSA-FL-Luc transfected LNCaP cells.In tumor bearing mice with or without emasculation,pPSA-FL-Lue piasmid was applied to monitored tumor growth and metastasis based on bioluminescence imaging.Conclusions:We construct a pPSA-FL-Luc piasmid,which stably expresses luciferase and can be applied to monitor tumor development in a prostate SCID mouse model.

The biotransformation of PCBs in three niches with contrasting redox conditions (water–soil interface, rhizosphere and non-rhizosphere subsoil) was studied using rhizoboxes subjected to the sequential flooding and draining conditions associated with rice cultivation in paddy fields. Rice cultivation favored PCB dechlorination and further transformation of the degradation products. Microbial dechlorination activity not only began earlier but was also 50% greater in the rhizosphere in comparison with bulk soil. Distinct profiles of both phospholipid fatty acids (PLFAs) and PCB congeners arose in each niche. Signature PLFAs attributed to Gram-positive (G+) bacteria were significantly correlated with the dissipation of PCB congeners in paddy field soils, especially in the rhizosphere.

The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell renal cell carcinoma (RCC) and normal kidney tissues. Next, γ-secretase inhibitor was used to suppress the Notch pathway in renal carcinoma cell lines. The proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis was performed to determine the apoptosis, as well as cell cycle alteration. The expression of Notch1 and Jagged1 proteins was detected to be higher in tumor tissues than in non-neoplastic tissues by western blot analysis. The positive staining rates of Notch1 and Jagged1 in clear cell RCC were higher than in normal kidney tissues [95.3 vs. 36.4% (P<0. 05); 93.0 vs. 42.4% (P<0.05), respectively]. The expression levels of Notch1 and Jagged1 were found to statistically correlate with tumor size, grade, TNM stage and disease relapse. The suppression of the Notch pathway was associated with cell proliferation inhibition, as well as induced G2/M phase cell cycle arrest and cell apoptosis. The Notch pathway may be important in oncogenesis of clear cell RCC and the γ-secretase inhibitor may be a potential agent for target therapy of RCC.

The environmental pollution and health risks caused by the improper disposal of electric and electronic waste (e-waste) have become urgent issues for the developing countries. One of the typical pollutants, polychlorinated biphenyls (PCBs), is commonly found in farmland in Taizhou, a major hotspot of e-waste recycling in China. This study investigated the amount of PCB residue in local farmlands. Biotransformation of PCBs was further studied under different water management conditions in paddy field with or without rice cultivation, with a special focus on the alternating flooded and drying processes. It was found that paddy field improved the attenuation of PCBs, especially for highly chlorinated congeners. In the microcosm experiment, 40% or more of the initial total PCBs was removed after sequential flood–drying treatments, compared to less than 10% in the sterilized control and 20% in the constant-drying system. Variation in the quantity of PCBs degrading and dechlorinating bacterial groups were closely related to the alteration of anaerobic–aerobic conditions. These results suggested that alternating anoxic–oxic environment in paddy field led to the sequential aerobic–anaerobic transformation of PCBs, which provided a favorable environment for natural PCB attenuation.

Six bacteria strains of which total nitrogen removal efficiency is over 70% were isolated from the activated sludge after enrichment culture.The strain Z31 with higher nitrogen removal was selected and its characteristic of aerobic denitrification was confirmed by the nitrogen element track.The results showed that the nitrate in the culture could be efficiently removed by strain Z31 and the nitrate nitrogen removal rate was up to above 95%.There was obvious nitrite accumulation during the denitrification process.Moreover, medium pH was increased and medium ORP was decreased as a result of denitrification.According to the morphological observation, physiological biochemical test and sequence analysis of the 16S rDNA, strain Z31 was identified as Pseudomonas stutzeri.And the phylogentic position of the strain was performed based on the phylogenetic tree.