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With the swift advancement of wearable electronics and artificial intelligence, the integration of electronic devices with the human body has advanced significantly, leading to enhanced real-time health monitoring and remote disease diagnosis. Despite progress in developing stretchable materials with skin-like mechanical properties, there remains a need for materials that also exhibit high optical transparency. Supercapacitors, as promising energy storage devices, offer advantages such as portability, long cycle life, and rapid charge/discharge rates, but achieving high capacity, stretchability, and transparency simultaneously remains challenging. This study combines the stretchable, transparent polymer PEDOT:PSS with MnO 2 nanoparticles to develop high-performance, stretchable, and transparent supercapacitors. PEDOT:PSS films were deposited on a PDMS substrate using a spin-coating method, followed by electrochemical deposition of MnO 2 nanoparticles. This method ensured that the nanosized MnO 2 particles were uniformly distributed, maintaining the transparency and stretchability of PEDOT:PSS. The resulting PEDOT:PSS/MnO 2 nanoparticle electrodes were gathered into a symmetric device using a LiCl/PVA gel electrolyte, achieving an areal capacitance of 1.14 mF cm -2 at 71.2% transparency and maintaining 89.92% capacitance after 5000 cycles of 20% strain. This work presents a scalable and economical technique to manufacturing supercapacitors that combine high capacity, transparency, and mechanical stretchability, suggesting potential applications in wearable electronics.

Main Conclusion: In this study, we assembled the first complete mitochondrial genome of Setaria italica and confirmed the multi-branched architecture. The foxtail millet (Setaria italica) holds significant agricultural importance, particularly in arid and semi-arid regions. It plays a pivotal role in diversifying dietary patterns and shaping planting strategies. Although the chloroplast genome of S. italica has been elucidated in recent studies, the complete mitochondrial genome remains largely unexplored. In this study, we employed PacBio HiFi sequencing platforms to sequence and assemble the complete mitochondrial genome. The mitochondrial genome spans a total length of 446,614 base pairs and harbors a comprehensive set of genetic elements, including 33 unique protein-coding genes (PCGs), encompassing 24 unique mitochondrial core genes and 9 variable genes, along with 20 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. Our analysis of mitochondrial PCGs revealed a pronounced codon usage preference. For instance, the termination codon exhibits a marked preference for UAA, while alanine (Ala) exhibits a preference for GCU, and glutamine (Gln) favors CAA. Notably, the maximum Relative Synonymous Codon Usage (RSCU) values for cysteine (Cys) and phenylalanine (Phe) are both below 1.2, indicating a lack of strong codon usage preference for these amino acids. Phylogenetic analyses consistently place S. italica in close evolutionary proximity to Chrysopogon zizanioides, relative to other Panicoideae plants. Collinearity analysis showed that a total of 39 fragments were identified to display homology with both the mitochondrial and chloroplast genomes. A total of 417 potential RNA-editing sites were discovered across the 33 mitochondrial PCGs. Notably, all these editing events involved the conversion of cytosine (C) to uracil (U). Through the employment of PCR validation coupled with Sanger sequencing for the anticipated editing sites of these codons, RNA-editing events were conclusively identified at two specific loci: nad4L-2 and atp6-1030. The results of this study provide a pivotal foundation for advanced genomic breeding research in foxtail millet. Furthermore, they impart essential insights that will be instrumental for forthcoming investigations into the evolutionary and molecular dynamics of Panicoideae species., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the evolving landscape of portable electronics, there is a critical demand for components that meld stretchability with optical transparency, especially in supercapacitors. Traditional materials fall short in harmonizing conductivity, stretchability, transparency, and capacity. Although poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) stands out as an exemplary candidate, further performance enhancements are necessary to meet the demands of practical applications. This study presents an innovative and effective method for enhancing electrochemical properties by homogeneously incorporating Ru(III) into PEDOT:PSS. These Ru(III) PEDOT:PSS complexes are readily synthesized by dipping PEDOT:PSS films in RuCl 3 solution for no longer than one minute, leveraging the high specific capacitance of Ru(III) while minimizing interference with transmittance. The supercapacitor made with this Ru(III) PEDOT:PSS complex demonstrated an areal capacitance of 1.62 mF cm -2 at a transmittance of 73.5%, which was 155% higher than that of the supercapacitor made with PEDOT:PSS under comparable transparency. Notably, the supercapacitor retained 87.8% of its initial capacitance even under 20% tensile strain across 20,000 cycles. This work presents a blueprint for developing stretchable and transparent supercapacitors, marking a significant stride toward next-generation wearable electronics.

Drought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis-antenna proteins, nitrogen metabolism, plant-pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5'-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.

Introduction: Breast cancer is a significant cause of mortality in women globally, and current treatment approaches face challenges due to side effects and drug resistance. Nanotechnology offers promising solutions by enabling targeted drug delivery and minimizing toxicity to normal tissues. Methods: In this study, we developed a composite platform called (Alg-AgNPs-CisPt), consisting of silver nanoparticles coated with an alginate hydrogel embedding cisplatin. We examined the effectiveness of this nanocomplex in induce synergistic cytotoxic effects on breast cancer cells. Results and Discussion: Characterization using various analytical techniques confirmed the composition of the nanocomplex and the distribution of its components. Cytotoxicity assays and apoptosis analysis demonstrated that the nanocomplex exhibited greater efficacy against breast cancer cells compared to AgNPs or cisplatin as standalone treatments. Moreover, the nanocomplex was found to enhance intracellular reactive oxygen species levels, further validating its efficacy. The synergistic action of the nanocomplex constituents offers potential advantages in reducing side effects associated with higher doses of cisplatin as a standalone treatment. Overall, this study highlights the potential of the (Alg-AgNPs-CisPt) nanocomplex as a promising platform embedding components with synergistic action against breast cancer cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maher, Kalil, Liu, Sossey-Alaoui and Bayachou.)

In actual production environments, antibiotic-resistant genes (ARGs) are abundant in pig manure, which can form transmission chains through animals, the environment, and humans, thereby threatening human health. Therefore, based on metagenomic analysis methods, ARGs and mobile genetic elements (MGEs) were annotated in pig manure samples from 6 pig farms in 3 regions of Shanxi Province, and the potential hosts of ARGs were analyzed. The results showed that a total of 14 ARG types were detected, including 182 ARG subtypes, among which tetracycline, phenol, aminoglycoside, and macrolide resistance genes were the main ones. ARG profiles, MGE composition, and microbial communities were significantly different in different regions as well as between different pig farms. In addition, Anaerobutyricum, Butyrivibrio, and Turicibacter were significantly associated with multiple ARGs, and bacteria such as Prevotella, Bacteroides, and the family Oscillospiraceae carried multiple ARGs, suggesting that these bacteria are potential ARG hosts in pig manure. Procrustes analysis showed that bacterial communities and MGEs were significantly correlated with ARG profiles. Variation partitioning analysis results indicated that the combined effect of MGEs and bacterial communities accounted for 64.08% of resistance variation and played an important role in ARG profiles. These findings contribute to our understanding of the dissemination and persistence of ARGs in actual production settings, and offer some guidance for the prevention and control of ARGs contamination., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate the population structure of environmental bacteria and fungi in three different types of medical institutions and the potential risks due to antibiotic resistance during the coronavirus disease 2019 (COVID-19) pandemic., Methods: One hundred twenty-six environmental surface samples were collected from three medical institutions during the COVID-19 pandemic. A total of 6,093 and 13,514 representative sequences of 16S and ITS ribosomal RNA (rRNA) were obtained by amplicon sequencing analysis. The functional prediction was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States tool based on the Greengenes database and the FAPROTAX database., Results: On environmental surfaces in three medical institutions during the COVID-19 pandemic, Firmicutes (51.6%) and Bacteroidetes (25%) were the dominant bacteria, while Ascomycota (39.4%) and Basidiomycota (14.2%) were the dominant fungi. A number of potential bacterial and fungal pathogens were successfully identified by the metagenomic approach. Furthermore, compared with the bacterial results, the fungi showed a generally closer Bray Curtis distance between samples. The overall ratio of Gram-negative bacteria to Gram-positive bacteria was about 3:7. The proportion of stress-tolerant bacteria in medical institutions A, B and C reached 88.9, 93.0 and 93.8%, respectively. Anaerobic bacteria accounted for 39.6% in outdoor environments, 77.7% in public areas, 87.9% in inpatient areas and 79.6% in restricted areas. Finally, the β-Lactam resistance pathway and polymyxin resistance pathway were revealed through functional prediction., Conclusion: We described the microbial population structure changes in three different types of medical institutions using the metagenomic approach during the COVID-19 pandemic. We found that the disinfection measures performed by three healthcare facilities may be effective on the "ESKAPE" pathogens, but less effective on fungal pathogens. Moreover, emphasis should be given to the prevention and control of β-lactam and polymyxin antibiotics resistance bacteria during the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Wu, Liu, Shen, Geng, Zhang, Zhou, Jiang, Gong, Fan and Ji.)

Background: Pelvic floor muscle training (PFMT) is a first-line conservative therapy for stress urinary incontinence (SUI). Electroacupuncture (EA) has been used to treat SUI recently., Objective: To compare the effectiveness of PFMT + EA versus PFMT + sham EA for SUI in women., Design, Setting, and Participants: A prospective, multicenter, randomized, controlled clinical trial was conducted at four hospitals in China involving 304 women with SUI from May 20, 2014 to November 21, 2017. Data were analyzed from April 20 to December 21, 2018., Intervention: Participants were randomized to receive 8 wk of PFMT+ EA (n = 154) or PFMT + sham EA (n = 150)., Outcome Measurements and Statistical Analysis: The primary outcome was the change in the amount of urine leakage measured on a 1-hr pad test. Student's t test, the χ 2 test, and the Wilcoxon rank-sum test were used for data analysis., Results and Limitations: Among the 304 participants randomized, 286 completed the study. The mean age was 57.6 yr (standard deviation [SD] 8.9) for the PFMT + sham EA group and 57.2 yr (SD 9.1) for the PFMT + EA group. The mean urine leakage at baseline was 13.6 g for the PFMT + sham EA group and 13.9 g for the PFMT + EA group. After the 8-wk intervention, the PFMT + EA group had a greater decrease in mean urine leakage (-9.8 g) than the PFMT + sham EA group (-5.8 g) with a mean difference of 4.0 g (95% confidence interval [CI] 0.8-7.2). Significantly more patients experienced a ≥50% reduction in urine leakage and the mean number of incontinence episodes in 24 h in the PFMT + EA group than in the PFMT + sham EA group (26.3%, 95%CI 15.8-36.8%). The PFMT + EA group experienced better improvement in participant-reported SUI severity at 6 wk (p < 0.001) and 8 wk (p < 0.001) and self-evaluated therapeutic effects at 2-32 wk (p < 0.001) after the intervention. Lack of measurement of the amount of urine leakage during follow-up is a limitation., Conclusions: In this randomized clinical trial, 8-wk combined treatment with PFMT + EA led to a greater improvement in SUI symptoms and better outcomes than with PFMT + sham EA., Patient Summary: We evaluated the effectiveness and safety of pelvic floor muscle training combined with electroacupuncture for stress urinary incontinence in women, Our results show that this is a promising therapeutic approach for the treatment of stress urinary incontinence., (Copyright © 2022. Published by Elsevier B.V.)

Viruses are ubiquitous in the gut of animals and play an important role in the ecology of the gut microbiome. The potential effects of these substances on the growth and development of the body are not fully known. Little is known about the effects of breeding environment on pig gut virome. Here, there are 3584 viral operational taxonomic units (vOTUs) longer than 5 kb identified by virus-enriched metagenome sequencing from 25 pig fecal samples. Only a small minority of vOTUs (11.16%) can be classified at the family level, and ∼50% of the genes could be annotated, supporting the concept of pig gut as reservoirs of substantial undescribed viral genetic diversity. The composition of pig gut virome in the six regions may be related to geography. There are only 20 viral clusters (VCs) shared among pig gut virome in six regions of Shanxi Province. These viruses rarely carry antibiotic resistance genes (ARGs). At the same time, they possess abundant auxiliary metabolic genes (AMGs) potentially involved in carbon, sulfur metabolism and cofactor biosynthesis, etc. This study has revealed the unique characteristics and potential function of pig gut DNA virome and established a foundation for the recognition of the viral roles in gut environment., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

Preclinical and human studies on the relationship between obesity/metabolic syndrome (MetS) and lower urinary tract dysfunction (LUTD) are inconsistent. We compared the temporal effects of feeding four different diets used to induce obesity/MetS, including 60% fructose, 2% cholesterol +10% lard, 30% fructose + 20% lard, or 32.5% lard diet, up to 42 wk, on metabolic parameters and bladder function in male Sprague-Dawley rats. Rats fed a 30% fructose + 20% lard or 32.5% lard diet consumed less food (grams), but only the 32.5% lard diet group took in more calories. Feeding rats a 60% fructose or 30% fructose + 20% lard diet led to glucose intolerance and increased blood pressure. Higher body weight and increased cholesterol levels were observed in the rats maintained on a 2% cholesterol +10% lard diet, whereas exposure to a 32.5% lard diet affected most of the above parameters. Voiding behavior measurement showed that voiding frequency and the total voided volume were lower in the experimental diet groups except for the 30% fructose + 20% lard group. The mean voided volume was lower in the 30% fructose + 20% lard and 32.5% lard groups compared with the control group. Cystometric analysis revealed a decreased bladder capacity, mean voided volume, intermicturition interval, and compliance in the 32.5% lard diet group. In conclusion, experimental diets including 60% fructose, 30% fructose + 20% lard, or 2% cholesterol + 10% lard diet differently affected physiological and metabolic parameters and bladder function to a limited extent, while exposure to a 32.5% lard diet had a greater impact.

The inhibitory effects of delphinidin-3-O-galactoside (DG) on the activities of tyrosinase (EC 1.14.18.1) (TY) from the edible Agaricus bisporus mushroom were investigated by enzyme kinetics, multispectroscopic methods, and molecular docking. As a result, DG showed strong inhibition on TY with the IC 50 of 34.14 × 10 -6  mol L -1 . The inhibition mode of DG against TY was mixed type with α values of 5.09. The binding constant K a and related thermodynamic parameters at the three different temperatures showed that the fluorescence quenching of TY by DG was static quenching. Synchronous fluorescence, three-dimensional fluorescence, ultraviolet-visible spectroscopy, and circular dichroism spectroscopies confirmed that the conformation or microenvironment of the TY protein were changed after binding with DG. Molecular docking revealed that DG had strong binding affinity to TY through hydrogen bonding and van der Waals force, and the results were consistent with the fluorescence data. Our findings suggested that DG may be potential TY inhibitor., (© 2021 International Union of Biochemistry and Molecular Biology, Inc.)

Dysfunction of the lower urinary tract (LUT) including urinary bladder and urethra (and prostate in men) is one of the most frequent complications of diabetes and can manifest as overactive bladder, underactive bladder, urinary incontinence, and as aggravated symptoms of benign prostate hyperplasia. We have performed a selective literature search to review existing evidence on efficacy of classic medications for the treatment of LUT dysfunction in diabetic patients and animals, i.e., α 1 -adrenoceptor and muscarinic receptor antagonists, β 3 -adrenoceptor agonists, and phosphodiesterase type 5 inhibitors. Generally, these agents appear to have comparable efficacy in patients and/or animals with and without diabetes. We also review effects of antidiabetic medications on LUT function. Such studies have largely been performed in animal models. In the streptozotocin-induced models of type 1 diabetes, insulin can prevent and reverse alterations of morphology, function, and gene expression patterns in bladder and prostate. Typical medications for the treatment of type 2 diabetes have been studied less often, and the reported findings are not yet sufficient to derive robust conclusions. Thereafter, we review animal studies with emerging medications perhaps targeting diabetes-associated LUT dysfunction. Data with myoinositol, daidzein, and with compounds that target oxidative stress, inflammation, Rac1, nerve growth factor, angiotensin II receptor, serotonin receptor, adenosine receptor, and soluble guanylyl cyclase are not conclusive yet, but some hold promise as potential treatments. Finally, we review nonpharmacological interventions in diabetic bladder dysfunction. These approaches are relatively new and give promising results in preclinical studies. In conclusion, the insulin data in rodent models of type 1 diabetes suggest that diabetes-associated LUT function can be mostly or partially reversed. However, we propose that considerable additional experimental and clinical studies are needed to target diabetes itself or pathophysiological changes induced by chronic hyperglycemia for the treatment of diabetic uropathy., (© 2022. The Author(s).)

CCT transcription factors are involved in the regulation of photoperiod and abiotic stress in Arabidopsis and rice. It is not clear that how CCT gene family expand and regulate heading date in foxtail millet. In this study, we conducted a systematic analysis of the CCT gene family in foxtail millet. Thirty-nine CCT genes were identified and divided into four subfamilies based on functional motifs. Analysis showed that dispersed duplication played a predominant role in the expansion of CCT genes during evolution. Nucleotide diversity analysis suggested that genes in CONSTANS ( COL )-like, CCT MOTIF FAMILY ( CMF )-like, and pseudoresponse response regulator (PRR)-like subfamilies were subjected to selection. Fifteen CCT genes were colocalized with previous heading date quantitative trait loci (QTL) and genome-wide association analysis (GWAS) signals. Transgenic plants were then employed to confirm that overexpression of the CCT gene SiPRR37 delayed the heading date and increased plant height. Our study first investigated the characterization and expansion of the CCT family in foxtail millet and demonstrated the role of SiPRR37 . These results lay a significant foundation for further research on the function of CCT genes and provide a cue for the regulation of heading date., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ma, Wang, Li, Wang, Wang, Jiang, Liu, Liu, Liu, Cheng, Wang, Wei and Yao.)

5-lipoxygenase (5-LOX) was a key enzyme involved in many inflammatory diseases. Sec-O-glucosylhamaudol (SOG) was a chromone found in Saposhnikovia divaricata (Turcz.) Schischk (S. divaricate). The potato-derived 5-LOX (p-5-LOX) and human recombinant 5-LOX (h-5-LOX) were selected as model protein due to their simple usability and high stability in this study. Thus, the binding interactions of p-5-LOX and h-5-LOX with SOG were investigated by multi-spectroscopy and molecular docking. As a result, the fluorescence intensities of the two 5-LOX were quenched statically by SOG. However, the binding ability of SOG to h-5-LOX was higher than that of p-5-LOX at the same temperature. The results of multi-spectroscopy revealed that the conformation and micro-environment of the two 5-LOX proteins were changed after binding with SOG. Fluorescence assay and molecular docking indicated that hydrogen bond and electrostatic gravitation were the main forces between the two 5-LOX and SOG. Our results here suggested that SOG may exert anti-inflammatory effect by inhibiting 5-LOX activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aging and major chronic diseases are risk factors for lower urinary tract symptoms (LUTS). On the other hand, oxidative stress (OS) is one of the fundamental mechanisms of aging and the development of chronic diseases. Therefore, OS might be a candidate mechanism linking these two clinical entities. This article aims to summarize the studies on the prevalence of LUTS, the role of OS in aging and chronic diseases, and the potential mechanisms supporting the putative link. A comprehensive literature search was performed to identify recent reports investigating LUTS and OS in major chronic diseases. In addition, studies on the impact of OS on the lower urinary tract, including bladder, urethra, and prostate, were collected and summarized. Many studies showed LUTS are prevalent in aging and major chronic diseases, including obesity, metabolic syndrome, diabetes, cardiovascular disease, hypertension, obstructive sleep apnea, autoimmune diseases, Alzheimer's disease, and Parkinson's disease. At the same time, OS is a key component in the pathogenesis of those chronic diseases and conditions. Recent studies also provided evidence that exacerbated OS can cause functional and/or structural changes in the bladder, urethra, and prostate, leading to LUTS. The reviewed data support the concept that OS is involved in multiple risk factors-associated LUTS, although further studies are needed to confirm the causative relationship. The specific ROS/RNS and corresponding reactions/pathways involved in chronic diseases and associated LUTS should be identified in the future and could serve as therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Elrashidy, Li and Liu.)

Astilbin, isoastilbin and neoastilbin are the three flavonoid isomers prevalent in Rhizoma Smilax glabra. The interactions between human cytochrome P450 2D6 (CYP2D6) and the three isomers were investigated by multiple spectroscopic coupled with molecular docking. As a result, the fluorescence intensity of CYP2D6 was quenched statically by the three isomers. Meanwhile, astilbin had the strongest binding ability to CYP2D6, followed by isoastilbin and neoastilbin under the identical temperature. Synchronous fluorescence, three-dimensional fluorescence, ultraviolet-visible spectroscopy, circular dichroism and Fourier-transform infrared spectra confirmed that the conformation and micro-environment of CYP2D6 protein were changed after binding with the three isomers. As suggested from molecular docking, the three isomers had strong binding affinity to CYP2D6 via the bonding of hydrogen and van der Waals forces, and the results were in agreement with the fluorescence results. The findings here suggested that astilbin, isoastilbin and neoastilbin may cause the herb-drug interactions for their inhibition of CYP2D6 activity., (© 2021 John Wiley & Sons Ltd.)

Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug-drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh-performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the K m values were 18.9 and 36.4 μM and the V max values were 0.02 and 0.20 μM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC 50 values of 2.63, 3.03 and 6.51 μM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC 50 values of 1.48, 11.87 and 14.16 μM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug-drug interactions by affecting the activities of CYP3A4 and 2D6., (© 2020 John Wiley & Sons, Ltd.)

As typical bacterial replicons, circular chromosomes replicate bidirectionally and circular plasmids replicate either bidirectionally or unidirectionally. Whereas the finding of chromids (plasmid-derived chromosomes) in multiple bacterial lineages provides circumstantial evidence that chromosomes likely evolved from plasmids, all experimentally assayed chromids were shown to use bidirectional replication. Here, we employed a model system, the marine bacterial genus Pseudoalteromonas , members of which consistently carry a chromosome and a chromid. We provide experimental and bioinformatic evidence that while chromids in a few strains replicate bidirectionally, most replicate unidirectionally. This is the first experimental demonstration of the unidirectional replication mode in bacterial chromids. Phylogenomic and comparative genomic analyses showed that the bidirectional replication evolved only once from a unidirectional ancestor and that this transition was associated with insertions of exogenous DNA and relocation of the replication terminus region ( ter2 ) from near the origin site ( ori2 ) to a position roughly opposite it. This process enables a plasmid-derived chromosome to increase its size and expand the bacterium's metabolic versatility while keeping its replication synchronized with that of the main chromosome. A major implication of our study is that the uni- and bidirectionally replicating chromids may represent two stages on the evolutionary trajectory from unidirectionally replicating plasmids to bidirectionally replicating chromosomes in bacteria. Further bioinformatic analyses predicted unidirectionally replicating chromids in several unrelated bacterial phyla, suggesting that evolution from unidirectionally to bidirectionally replicating replicons occurred multiple times in bacteria. IMPORTANCE Chromosome replication is an essential process for cell division. The mode of chromosome replication has important impacts on the structure of the chromosome and replication speed. Bidirectional replication is the rule for bacterial chromosomes, and unidirectional replication has been found only in plasmids. To date, no bacterial chromosomes have been experimentally demonstrated to replicate unidirectionally. Here, we showed that the chromids (plasmid-derived chromosomes) in Pseudoalteromonas replicate either uni- or bidirectionally and that a single evolutionary transition from uni- to bidirectionality explains this diversity. These uni- and bidirectionally replicating chromids likely represent two stages during the evolution from a small and unidirectionally replicating plasmid to a large and bidirectionally replicating chromosome. This study provides insights into both the physiology of chromosome replication and the early evolutionary history of bacterial chromosomes., (Copyright © 2021 Xie et al.)

Objective: To observe whether urethral injection of chemokine (c-c motif) ligand 7 (CCL7) and overexpressing CC receptor 1 (CCR1) in mesenchymal stem cells (MSCs) can promote their homing and engraftment to the injured tissue, and improve the recovery of simulated birth injury-induced stress urinary incontinence (SUI) in rats. Methods: Female rats underwent a dual injury consisting of vaginal distension (VD) and pudendal nerve crush (PNC) to induce SUI. Bone marrow-derived MSCs were transduced with lentivirus carrying CCR1 (MSC-CCR1) and green fluorescent protein (GFP). Forty virgin Sprague-Dawley rats were evenly distributed into four groups: sham SUI + MSC-CCR1+CCL7, SUI + MSCs, SUI + MSC-CCR1, and SUI + MSC-CCR1+CCL7 group. The engrafted MSCs in urethra were quantified. Another three groups of rats, including sham SUI + sham MSC-CCR1+CCL7 treatment, SUI + sham MSC-CCR1+CCL7 treatment, and SUI + MSC-CCR1+CCL7 treatment group, were used to evaluate the functional recovery by testing external urethral sphincter electromyography (EUS EMG), pudendal nerve motor branch potentials (PNMBP), and leak point pressure (LPP) 1 week after injury and injection. Urethra and vagina were harvested for histological examination. Results: The SUI + MSC-CCR1+CCL7 group received intravenous injection of CCR1-overexpressing MSCs and local injection of CCL7 after simulated birth injury had the most engraftment of MSCs to the injured tissues and best functional recovery from SUI compared to other groups. Histological examination showed a partial repair in the SUI + MSC-CCR1+CCL7 group. Conclusions: Our study demonstrated combined treatment with CCR1-overexpressing MSCs and CCL7 can increase engraftment of MSCs and promote the functional recovery of simulated birth trauma-induced SUI in rats, which could be a new therapeutic strategy for SUI., (Copyright © 2020 Jiang, Ji, Li, Song, Bano, Chen, Liu and Wang.)

As a major bioactive compound from the Saposhnikovia divaricata (Turcz.) Schischk, sec-O-glucosylhamaudol (SOG), has been reported to have anti-nociceptive activity and high 5-lipoxygenase (5-LOX) activity. Nevertheless, the mechanism of the potential anti-inflammatory effects of SOG is unclear. The anti-inflammatory impacts of SOG in RAW 264.7 cell lines stimulated by LPS were explored in the present study. It was found that SOG dose-dependently reduced the emergence of inflammation cytokines, such as IL-6 and TNF-α in Raw264.7 murine macrophages stimulated by LPS. Real-time PCR assay demonstrated the SOG dose-dependently inhibited transcription of these cytokines as well. In addition, it was also found that NF-κB activation and MAPKs phosphorylation including p38, JNK and ERK1/2 induced by LPS were suppressed by SOG. Due to its anti-inflammatory activity, our results suggest that SOG might have therapeutic effects on inflammatory disease, such as acute lung injury or rheumatoid arthritis., (© 2020 The Author(s).)

Diabetes induces time-dependent alterations in urinary bladders. Long-term diabetes causes an underactive bladder. However, the fundamental mechanisms are still elusive. This study aimed to examine the histological changes and the potential molecular pathways affected by long-term diabetes in the rat bladder. Diabetes was induced in 8-week-old male Lewis rats by streptozotocin, while age-matched control rats received citrate buffer only. Forty-four weeks after diabetes induction, bladders were harvested for histological and molecular analyses. The expressions of proteins related to fibrosis, apoptosis and oxidative stress as well as the cellular signaling pathway in the bladder were examined by immunoblotting. Histological examinations illustrated diabetes caused detrusor hypertrophy and fibrotic changes in the bladder. Immunoblotting analysis demonstrated higher collagen I but lower elastin expression in the bladder in diabetic rats. These were accompanied by an increase in the expression of transforming growth factor-beta1, along with the downregulation of matrix metalloptoteinase-1, and upregulation of tissue inhibitor of metalloproteinase-1. Diabetic rats showed an increase in nitrotyrosine, but decrease in nuclear factor erythroid-related factor 2 (Nrf2) levels in the bladder. Enhanced apoptotic signaling was observed, characterized by increased expression of Bcl-2-associated X protein (Bax), decreased expression of Bcl-2, in the diabetic bladder. The nerve growth factor level was decreased in the diabetic bladder. A significant suppression in the protein expressions of phosphorylated extracellular signal-regulated kinases 1/2 was found in diabetic bladders. This study demonstrated that long-term diabetes caused molecular changes that could promote fibrosis and apoptosis in the bladder. Oxidative stress may be involved in this context., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this study, an accurate and reliable method of ultra-performance liquid chromatography coupled with a triple-quadrupole tandem mass spectrometry was firstly developed and fully validated for the simultaneous determination of epicatechin, neoastilbin, astilbin, isoastilbin, engeletin and resveratrol in rat plasma after administration of Smilacis glabrae Roxb. extract. Naringenin was used as an internal standard (IS). The analyte and IS were separated on a C 18 column by gradient elution with a mobile phase of acetonitrile-0.3% acetic acid at a flow rate of 0.25 mL/min for a total run time of 8 min. The method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect and stability. The developed method was successfully applied to determine the main pharmacokinetic parameters of six components in rat plasma., (© 2019 John Wiley & Sons, Ltd.)

Hybridization drives rapid speciation by shaping novel genotypic and phenotypic profiles. Genomic incompatibility and transcriptome shock have been observed in hybrids, although this is rarer in animals than in plants. Using the newly sequenced genomes of the blunt snout bream ( Megalobrama amblycephala [BSB]) and the topmouth culter ( Culter alburnus [TC]), we focused on the sequence variation and gene expression changes in the reciprocal intergeneric hybrid lineages (F 1 -F 3 ) of BSB × TC. A genome-wide transcriptional analysis identified 145-974 expressed recombinant genes in the successive generations of hybrid fish, suggesting the rapid emergence of allelic variation following hybridization. Some gradual changes of gene expression with additive and dominance effects and various cis and trans regulations were observed from F 1 to F 3 in the two hybrid lineages. These asymmetric patterns of gene expression represent the alternative strategies for counteracting deleterious effects of the subgenomes and improving adaptability of novel hybrids. Furthermore, we identified positive selection and additive expression patterns in transforming growth factor, beta 1b ( tgfb1b ), which may account for the morphological variations of the pharyngeal jaw in the two hybrid lineages. Our current findings provide insights into the evolution of vertebrate genomes immediately following hybridization., (© 2019 Ren et al.; Published by Cold Spring Harbor Laboratory Press.)

Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We tested the hypothesis that oxidative stress plays a key role in the development of diabetic bladder dysfunction using an inducible smooth muscle (SM)-specific superoxide dismutase 2 ( Sod2 ) gene knockout (SM- Sod2 KO) mouse model. Eight-week-old male Sod2 lox/lox , SM-CreER T2 (ki) Cre/+ mice and wild-type mice were assigned to diabetic or control groups. 4-Hydroxytamoxifen was injected into Sod2 lox/lox , SM-CreER T2 (ki) Cre/+ mice to activate CreER T2 -mediated deletion of Sod2 . Diabetes was induced by injection of streptozotocin, whereas control mice were injected with vehicle. Nine weeks later, bladder function was evaluated, and bladders were harvested for immunoblot analysis. Wild-type diabetic mice presented compensated bladder function along with increased nitrotyrosine and MnSOD in detrusor muscle. Induction of diabetes in SM- Sod2 KO mice caused deteriorated bladder function and even greater increases in nitrotyrosine compared with wild-type diabetic mice. Expression levels of apoptosis regulator Bax and cleaved caspase-3 were increased, but apoptosis regulator Bcl-2 expression was decreased in detrusor muscle of both diabetic groups, with more pronounced effects in SM- Sod2 KO diabetic mice. Our findings demonstrate that exaggerated oxidative stress can accelerate the development of bladder dysfunction in diabetic mice and the enhanced activation of apoptotic pathways in the bladder may be involved in the process.

Saccharina , as one of the most important brown algae (Phaeophyceae) with multicellular thallus, has a very remarkable evolutionary history, and globally accounts for most of the economic marine aquaculture production worldwide. Here, we present the 580.5 million base pairs of genome sequence of Saccharina japonica , whose current assembly contains 35,725 protein-coding genes. In a comparative analysis with Ectocarpus siliculosus , the integrated virus sequence suggested the genome evolutionary footprints, which derived from their co-ancestry and experienced genomic arrangements. Furthermore, the gene expansion was found to be an important strategy for functional evolution, especially with regard to extracelluar components, stress-related genes, and vanadium-dependent haloperoxidases, and we proposed a hypothesis that gene duplication events were the main driving force for the evolution history from multicellular filamentous algae to thallus algae. The sequenced Saccharina genome paves the way for further molecular studies and is useful for genome-assisted breeding of S. japonica and other related algae species.

A complete and accurate genome sequence provides a fundamental tool for functional genomics and DNA-informed breeding. Here, we assemble a high-quality genome (contig N50 of 6.99 Mb) of the apple anther-derived homozygous line HFTH1, including 22 telomere sequences, using a combination of PacBio single-molecule real-time (SMRT) sequencing, chromosome conformation capture (Hi-C) sequencing, and optical mapping. In comparison to the Golden Delicious reference genome, we identify 18,047 deletions, 12,101 insertions and 14 large inversions. We reveal that these extensive genomic variations are largely attributable to activity of transposable elements. Interestingly, we find that a long terminal repeat (LTR) retrotransposon insertion upstream of MdMYB1, a core transcriptional activator of anthocyanin biosynthesis, is associated with red-skinned phenotype. This finding provides insights into the molecular mechanisms underlying red fruit coloration, and highlights the utility of this high-quality genome assembly in deciphering agriculturally important trait in apple.

The Amur ide (Leuciscus waleckii) is a cyprinid fish that is widely distributed in Northeast Asia. The Lake Dali Nur population inhabits one of the most extreme aquatic environments on Earth, with an alkalinity up to 50 mmol/L (pH 9.6), thus providing an exceptional model with which to characterize the mechanisms of genomic evolution underlying adaptation to extreme environments. Here, we developed the reference genome assembly for L. waleckii from Lake Dali Nur. Intriguingly, we identified unusual expanded long terminal repeats (LTRs) with higher nucleotide substitution rates than in many other teleosts, suggesting their more recent insertion into the L. waleckii genome. We also identified expansions in genes encoding egg coat proteins and natriuretic peptide receptors, possibly underlying the adaptation to extreme environmental stress. We further sequenced the genomes of 10 additional individuals from freshwater and 18 from Lake Dali Nur populations, and we detected a total of 7.6 million SNPs from both populations. In a genome scan and comparison of these two populations, we identified a set of genomic regions under selective sweeps that harbor genes involved in ion homoeostasis, acid-base regulation, unfolded protein response, reactive oxygen species elimination, and urea excretion. Our findings provide comprehensive insight into the genomic mechanisms of teleost fish that underlie their adaptation to extreme alkaline environments., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Marinobacter psychrophilus strain 20041(T) was isolated from sea-ice of the Canadian Basin. Here we report the complete sequence of the 3.9-Mb genome of this strain. The complete genome sequence will facilitate the study of the physiology and evolution of Marinobacter species., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Accumulating evidences suggests that obesity and metabolic syndrome (MetS) contribute towards lower urinary tract symptoms (LUTS) through alterations in the phenotype of bladder and prostate gland. Clinical studies indicate a link between MetS and LUTS. Nevertheless, there is lack of suitable animal model(s) which could illustrate an association linking obesity to LUTS. We examined the lower urinary tract function in an obesity-initiated MetS mouse model., Methods: Male C57BL/6N wild-type and obese B6.V-Lepob/J maintained on regular diet for 28 weeks were subjected to the assessment of body weight (BW), body length (BL), waist circumference (WC), body mass index (BMI), blood glucose (BG), plasma insulin (INS), plasma leptin (LEP), total cholesterol (CHO), free fatty acid (FFA), and measurement of urinary functions. Whole animal peritoneal and subcutaneous adipose tissue measurements as well as prostate and bladder volumes were analyzed by MRI followed by histological evaluation. These parameters were used to draw correlations between MetS and LUTS., Results: Obesity parameters such as BW, WC, and BMI were significantly higher in B6.V-Lepob/J mice compared to C57BL/6N mice (P < 0.01). Higher levels of total CHO and FFA were noted in B6.V-Lepob/J mice than C57BL/6N mice (P < 0.05). These results were concurrent with frequency, lower average urine volume and other urinary voiding dysfunctions in B6.V-Lepob/J mice. MRI assessments demonstrate marked increase in body fat and prostate volume in these mice. Compared to C57BL/6N mice, histological analysis of the prostate from B6.V-Lepob/J mice showed increased proliferation, gland crowding, and infiltration of immune cells in the stroma; whereas the bladder urothelium was slightly thicker and appears more proliferative in these mice. The regression and correlation analysis indicate that peritoneal fat (R = 0.853; P < 0.02), CHO (R = 0.729; P < 0.001), BG (R = 0.712; P < 0.001) and prostate volume (R = 0.706; P < 0.023) strongly correlate with LUTS whereas BMI, WC, INS, and FFA moderately correlate with the prevalence of bladder dysfunction., Conclusion: Our results suggest that LUTS may be attributable in part to obesity and MetS. Validation of an in vivo model may lead to understand the underlying pathophysiological mechanisms of obesity-related LUTS in humans. Prostate 76:964-976, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Draconibacterium orientale strain FH5(T) isolated from a marine sediment sample from coast of Weihai, China, was a new species within the proposed new genus Draconibacterium in class Bacteroidia. Here, we present the genome sequence of D. orientale FH5(T), which contains 5,132,075 bp with a G+C content of 41.31%. The genome sequence will contribute to a better understanding of the physiology of this species., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Manganese superoxide dismutase (MnSOD) is considered a critical component of the antioxidant systems that protect against oxidative damage. We are interested in the role of oxidative stress in bladder detrusor smooth muscle (SM) in different disease states. In this study, we generated an inducible, SM-specific Sod2(-/-) mouse model to investigate the effects of MnSOD depletion on the function of the bladder. We crossbred floxed Sod2 (Sod2(lox/lox)) mice with mice containing heterozygous knock-in of a gene encoding a tamoxifen-activated Cre recombinase in the SM22α promoter locus [SM-CreER(T2)(ki)(Cre/+)]. We obtained Sod2(lox/lox),SM-CreER(T2)(ki)(Cre/+) mice and injected 8-wk-old males with 4-hydroxytamoxifen to induce Cre-mediated excision of the floxed Sod2 allele. Twelve weeks later, SM-specific deletion of Sod2 and depletion of MnSOD were confirmed by polymerase chain reaction, immunoblotting, and immunohistochemistry. SM-specific Sod2(-/-) mice exhibited normal growth with no gross abnormalities. A significant increase in nitrotyrosine concentration was found in bladder SM tissue of SM-specific Sod2(-/-) mice compared with both wild-type mice and Sod2(+/+), SM-CreER(T2)(ki)(Cre/+) mice treated with 4-hydroxytamoxifen. Assessment of 24-h micturition in SM-specific Sod2(-/-) mice revealed significantly higher voiding frequency compared with both wild-type and SM-specific Cre controls. Conscious cystometry revealed significantly shorter intercontraction intervals and lower functional bladder capacity in SM-specific Sod2(-/-) mice compared with wild-type mice. This novel model can be used for exploring the mechanistic role of oxidative stress in organs rich in SM in different pathological conditions., (Copyright © 2015 the American Physiological Society.)

Diabetic individuals have increased susceptibility to urinary tract infection (UTI), a common, painful condition. During diabetes mellitus, non-enzymatic reactions between reducing sugars and protein amine groups result in excessive production of advanced glycation end products (AGEs) that accumulate in tissues. Since bacteria adhere to cell surfaces by binding to carbohydrates, we hypothesized that adherence of bacteria to the bladder in diabetics may be enhanced by accumulation of AGEs on urothelial surface proteins. Using a murine model of UTI, we observed increased adherence of type 1 fimbriated uropathogenic Escherichia coli (UPEC) to the bladder in streptozotocin-induced diabetic female mice compared with age-matched controls, along with increased concentrations of two common AGEs in superficial urothelial cells from diabetic bladders. Several lectins with different specificities exhibited increased binding to urothelial homogenates from diabetic mice compared with controls, and two of those lectins also bound to AGEs. Furthermore, mannose-binding type 1 fimbriae isolated from UPEC bound to different AGEs, and UPEC adherence to the bladder in diabetic mice, were inhibited by pretreatment of mice with the AGE inhibitor pyridoxamine. These results strongly suggest a role for urothelial AGE accumulation in increased bacterial adherence during UTI in diabetes., (© FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diabetic patients have increased susceptibility to infections, and urinary tract infections (UTI) are the most common type in women with diabetes mellitus. Knowledge of bacterial clearance effectiveness following UTI in diabetics is sparse. In this study, the effects of diabetes on bacterial clearance efficiency and components of the innate immune system in response to UTI in a murine model were investigated. Streptozotocin-induced diabetic and control female C57BL/6J mice were infected with uropathogenic Escherichia coli, and bacterial load, expression of chemokines, and neutrophil infiltration in the bladder over time were investigated. Expression levels of histone deacetylases were also measured to address a potential mechanism underlying the phenotype. Bacterial clearance during UTI was significantly prolonged in diabetic mice relative to controls. Neutrophil infiltration in bladder tissue and urine, and both mRNA and protein expression of chemokines MIP-2, KC, MCP-1 and IL-6 in bladder tissue were diminished at early time points after infection in diabetic mice relative to controls. In addition, mRNA levels of histone deacetylases 1-5 were increased in diabetic mice. This is the first study to show an association of impaired bacterial clearance in diabetic mice with suppression of UTI-induced chemokine expression and neutrophil infiltration in the bladder., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To further improve the efficiency of xylose fermentation by modifying the pentose phosphate pathway (PPP) and the aldehyde reductase gene h16&#95;A3186 in Ralstonia eutropha W50-EAB., Methods: The transketolase (tktA, cbbT2) and transaldolase (tal) gene were cloned from R. eutropha chromosome by PCR and inserted into expressing vector pBBR1MCS-3. The resulting recombinant plasmids were transformed into W50-EAB to generate W50-KAB, W50-CAB and W50-TAB, respectively. The aldehyde reductase gene h16&#95;A3186 was shortened from 834 bp to 135 bp by in-frame deletion from strain W50-E in which the xylE gene coding for xylose transporter was chromosomally integrated to construct recombinant strain W50'-E. Then the xylAB gene coding for xylose isomerase and xylulokinase from Escherichia coli were expressed in W50'-E to generate recombinant strain W50'-EAB. Recombinant plasmid pWL1-TAL was transformed into W50'-EAB to construct the strain W50'-TAB. The fermentation characteristics of the engineered strains were investigated., Results: The expression of tktA, cbbT2 and tal genes in R. eutropha W50-EAB was confirmed by enzyme assay. The deletion of h16&#95;A3186 gene was confirmed by PCR analysis and enzyme assay. Amplification of transketolase activity in R. eutropha W50-EAB showed negative effect on cell growth and D-xylose consumption. The recombinant strain W50-TAB and W50'-EAB exhibited a faster growth than W50-EAB with the maximum specific growth rate of 0.039 h(-1) and 0.040 h(-1), respectively, when cultivated on 0.1 mol/L D-xylose. And the PHB accumulation of W50-TAB and W50'-EAB reached 16.2 ± 1.01% and 19.8 ± 1.05% on the basis of cell dry weight, respectively. Furthermore, recombinant strain W50'-TAB exhibited better fermentation performance with the maximum specific growth rate of 0.042 h(-1) and PHB content of 27.9 ± 0.47%, respectively. Meanwhile, the recombinant strains W50-TAB, W50'-EAB and W50'-TAB showed higher biomass and more PHB accumulation when using glucose (0.01 mol/L) and D-xylose (0.09 mol/L) mixed sugars as fermentative substrate., Conclusion: Overexpression of the tal gene resulted in incressed D-xylose consumption. Deficiency of the aldehyde reductase relieved inhibition to D-xylose metabolism. Combination of the two strategies contributed to a higher efficiency of D-xylose utilisation and more PHB accumulation of the engineered R. eutropha strain.

Objective: To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs ≤ 4.0 cm)., Materials and Methods: Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek's funnel plot was used to evaluate the publication bias., Result: A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95 % CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95 % CI: 0.06-0.13), the pooled DOR was 296.52(95 % CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959 ± 0.0254., Conclusion: Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs ≤ 4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration.

High-Fat Diet (HFD) has emerged as an important risk factor not only for obesity and diabetes but also for urological disorders. Recent research provides ample evidence that HFD is a putative cause for prostatic diseases including prostate cancer. The mechanisms whereby these diseases develop in the prostate have not been fully elucidated. In this review we discuss signaling pathways intricately involved in HFD-induced prostate disease. We performed a search through PUBMED using key words "high fat diet" and "prostate". Our data and perspectives are included in this review along with research performed by various other groups. HFD is positively associated with an increased risk of benign prostatic hyperplasia (BPH) and prostate cancer. HFD induces oxidative stress and inflammation in the prostate gland, and these adverse influences transform it from a normal to a diseased state. Studies demonstrate that HFD accelerates the generation of reactive oxygen species by driving the NADPH oxidase system, exacerbating oxidative stress in the prostate. HFD also causes a significant increase in the levels of pro-inflammatory cytokines and gene products through activation of two important signaling pathways: the Signal Transducer and Activator of Transcription (STAT)-3 and Nuclear Factor-kappa B (NF-κB). Both these pathways function as transcription factors required for regulating genes involved in proliferation, survival, angiogenesis, invasion and inflammation. The crosstalk between these two pathways enhances their regulatory function. Through its influences on the NF-κB and Stat-3 signaling pathways, it appears likely that HFD increases the risk of development of BPH and prostate cancer.

Objective: To screen and identify the new long non-coding RNAs from transcriptome of laryngeal squamous cell cancer using strand-specific RNA-Seq technology and bioinformatics tools, and to analyze the difference expression of these LncRNAs., Methods: RNA was extracted from laryngeal squamous cell cancer tissues of 10 patients and the strand-specific libraries were constructed for high-throughput sequencing. The low-quality data were filtered and the high quality sequencing reads were mapped to the reference genome and assembled. The obtained transcripts were classified and annotated, the optimized LncRNA identification pipeline was used to discover novel LncRNA in these transcriptome, and the characteristics of LncRNA were analyzed., Results: A more optimized pipeline were established and 134 new LncRNA transcripts were found, which was not included in the public database. The new LncRNA transcripts had some characteristics in length distribution, ORF length, and expression., Conclusion: Some new LncRNA from the transcriptome of laryngeal carcinoma were identified, with different expression, and they may play an important role in laryngeal squamous cell cancer.

Objective: This study aimed to broaden the substrate spectrum of Ralstonia eutropha W50 to use D-xylose, which can produce poly-beta-hydroxybutyrates (PHB) at a high level., Methods: The D-xylose transporter gene xylE from Escherichia coli K-12 W3110 was cloned by PCR technique and integrated into the R. eutropha W50 chromosome. The recombinant strain W50-E was obtained. The D-xylose catabolic genes xylAB from E. coli K-12 W3110 and the promotor of PHA synthase gene phaC1 from R. eutropha H16 were cloned into pBBR1MCS to construct a recombinant plasmid. The plasmid was transformed into R. eutropha W50 and W50-E to generate the recombinant strains W50-AB and W50-EAB respectively. The characteristics of D-xylose utilization by W50-AB and W50-EAB were investigated., Results: The expression of xylA and xylB genes in R. eutropha W50 was confirmed by enzyme assay. The recombinant strain W50-AB could grow on 0.1 mol/L D-xylose with the maximum specific growth rate of 0.025 h(-1), but no growth and D-xylose consumption were observed when cultivated on 0.01 mol/L D-xylose. The recombinant strain W50-EAB exhibited a faster growth than W50-AB on 0.1 mol/L D-xylose, with the maximum specific growth rate of 0.035 h(-1). Furthermore, it exhibited a slow but defined growth and D-xylose consumption on 0.01 mol/L D-xylose. The PHB content assay showed that both recombinant strains accumulated a small amount of PHB, with a proportion of 15.07 +/- 1.01% and 15.07 +/- 1.64% on the basis of dry cell weight respectively, by using D-xylose (0.1 mol/L) as substrate. And their final D-xylose-PHB conversion rates were 0.0920 g x g(-1) and 0.0838 g x g(-1) respectively, which were much lower than their glucose-PHB conversion rates( > 0.22 g x g(-1)). However, the recombinant strains W50-AB and W50-EAB exhibited better fermentation performance and more PHB accumulation when using glucose(0.01 mol/L) and D-xylose (0.09 mol/L) mixed sugars as fermentative substrate., Conclusion: The recombinant strain W50-AB can metabolize D-xylose by the expression of xylAB genes, and the further expression of xylE gene is able to improve its D-xylose consumption rate. Meanwhile, the two recombinant strains can accumulate a small amount of PHB by using D-xylose as the sole carbon source.

Objective: To review studies on diabetic bladder dysfunction (DBD), a common and bothersome complication of diabetes mellitus., Data Sources: We performed a search of the English literature through PubMed. The key words used were "diabetes" and "bladder dysfunction" or "cystopathy". Our own data and perspective are included in the discussion., Study Selection: Studies containing data relevant to DBD were selected. Because of the limited length of this article, we also referenced reviews that contain comprehensive amalgamations of relevant literature., Results: The classic symptoms of DBD are decreased bladder sensation, increased bladder capacity, and impaired bladder emptying with resultant elevated post-void residual urine. However, recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes. Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes, causing an early phase of compensatory bladder function and a later phase of decompensated bladder function. The pathophysiology of DBD is multifactorial, including disturbances of the detrusor, urothelium, autonomic nerves, and urethra. Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes. Polyuria causes significant bladder hypertrophy in the early stage of diabetes, whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function., Conclusions: DBD includes time-dependent and mixed manifestations. The pathological alterations include muscle, nerve, and urothelium. Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD. Treatments for DBD are limited. Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately. Animal studies of DBD in type 2 diabetes are needed, from the natural history to mechanisms. Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.

Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super ability of carbon source biosynthesis and catabolism. The comparative transcriptome analysis from three culture conditions revealed the landscape of gene-altered expressions responsible for lipid accumulation. The LD proteomes further identified the proteins that mediate lipid synthesis, storage and other biological functions. Integrating these three omics uncovered 177 proteins that may be involved in lipid metabolism and LD dynamics. A LD structure-like protein LPD06283 was further verified to affect the LD morphology. Our omics studies provide not only a first integrated omics study of prokaryotic LD organelle, but also a systematic platform for facilitating further prokaryotic LD research and biofuel development.

Objective: To broaden the substrate spectrum including L-arabinose, Ralstonia eutropha W50, a mutant strain with high yield of poly-beta-hydroxybutyrate (PHB), was metabolically engineered by expressing the genes encoding L-arabinose catabolic enzymes and high-affinity L-arabinose transporter from Escherichia coli., Methods: The promoter fragment of PHB synthase gene phaC1 (P(pha C1)) from R. eutropha H16 and the araBAD genes from E. coli W3110 were cloned by PCR and inserted into expression vector pBBR1 MCS. The resulting recombinant plasmid was transformed into W50 to generate W50-1. The araFGH gene from E. coli W3110 was introduced into W50-1 by plasmid system or homologous recombination, yielding W50-2 and W50-3 respectively. The fermentation characteristics of the three engineered strains were investigated., Results: The flask fermentation experiments of the engineered strains show that W50-1 carrying the arabinose catabolic genes under the control of P(pha C1) could grow in the fermentation medium containing 0.1 mol/L arabinose as the sole carbon source, but could not utilize low concentration arabinose (0.01 mol/L). However, W50-2 and W50-3 containing the gene of high-affinity arabinose transporter were able to utilize low concentration arabinose. In the fermentation medium containing 0.1 mol/L arabinose, the biomass of W50-3 was 2.5 fold higher than that of W50-1, and the PHB accumulation amount of W50-3 accounted for 38.6% of the cell dry weight., Conclusion: R. eutropha W50 was able to metabolize L-arabinose by the expression of araBAD genes, and the simultaneous expression of araFGH genes could further improve its ability of L-arabinose utilization. By using L-arabinose as the sole carbon source, the recombinant strain W50-3 can accumulate a noticeable level of PHB.

Purpose: Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats., Materials and Methods: A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder., Results: Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes., Conclusions: Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants.

Diabetes causes significant increases in bladder weight but the natural history and underlying mechanisms are not known. In this study, we observed the temporal changes of detrusor muscle cells (DMC) and the calcineurin (Cn) and Akt expressions in detrusor muscle in the diabetic rat. Male Sprague-Dawley rats were divided into 3 groups: streptozotocin-induced diabetics, 5% sucrose-induced diuretics, and age-matched controls. The bladders were removed 1, 2, or 9weeks after disease induction and the extent of hypertrophy was examined by bladder weights and cross sectional area of DMC. Cn and Akt expression were evaluated by immunoblotting. Both diabetes and diuresis caused significant increases in bladder weight. The mean cross sectional areas of DMC were increased in both diabetic and diuretic animals 1, 2, or 9weeks after disease induction. The expression levels of both the catalytic A (CnA) and regulatory B (CnB) subunits of Cn were increased at 1 and 2weeks, but not at 9weeks. Expression of Akt was similar among control, diabetic, and diuretic rat bladder at all time points. In conclusion, diabetes and diuresis induce similar hypertrophy of detrusor muscle during the first 9weeks, indicating that bladder hypertrophy in the early stage of diabetes is in response to the presence of increased urine output in diabetes. Our results suggest that the Cn, but not the Akt signaling pathway may be involved in the development of bladder hypertrophy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Animal genes of different lineages, such as vertebrates and arthropods, are well-organized and blended into dynamic chromosomal structures that represent a primary regulatory mechanism for body development and cellular differentiation. The majority of genes in a genome are actually clustered, which are evolutionarily stable to different extents and biologically meaningful when evaluated among genomes within and across lineages. Until now, many questions concerning gene organization, such as what is the minimal number of genes in a cluster and what is the driving force leading to gene co-regulation, remain to be addressed. Here, we provide a user-friendly database-LCGbase (a comprehensive database for lineage-based co-regulated genes)-hosting information on evolutionary dynamics of gene clustering and ordering within animal kingdoms in two different lineages: vertebrates and arthropods. The database is constructed on a web-based Linux-Apache-MySQL-PHP framework and effective interactive user-inquiry service. Compared to other gene annotation databases with similar purposes, our database has three comprehensible advantages. First, our database is inclusive, including all high-quality genome assemblies of vertebrates and representative arthropod species. Second, it is human-centric since we map all gene clusters from other genomes in an order of lineage-ranks (such as primates, mammals, warm-blooded, and reptiles) onto human genome and start the database from well-defined gene pairs (a minimal cluster where the two adjacent genes are oriented as co-directional, convergent, and divergent pairs) to large gene clusters. Furthermore, users can search for any adjacent genes and their detailed annotations. Third, the database provides flexible parameter definitions, such as the distance of transcription start sites between two adjacent genes, which is extendable to genes that flanking the cluster across species. We also provide useful tools for sequence alignment, gene ontology (GO) annotation, promoter identification, gene expression (co-expression), and evolutionary analysis. This database not only provides a way to define lineage-specific and species-specific gene clusters but also facilitates future studies on gene co-regulation, epigenetic control of gene expression (DNA methylation and histone marks), and chromosomal structures in a context of gene clusters and species evolution. LCGbase is freely available at http://lcgbase.big.ac.cn/LCGbase.

Using a pyrosequencing-based custom-made sequencer BIGIS-4, we sequenced a Gram-negative bacterium Glaciecola mesophila sp. nov. (Gmn) isolated from marine invertebrate specimens. We generated 152043 sequencing reads with a mean high-quality length of 406 bp, and assembled them using the BIGIS-4 post-processing module. No systematic low-quality data was detected beyond expected homopolymer-derived errors. The assembled Gmn genome is 5144318 bp in length and harbors 4303 annotated genes. A large number of metabolic genes correspond to various nutrients from surface marine invertebrates. Its abundant cold-tolerant and cellular signaling and related genes reveal a fundamental adaptation to low-temperature marine environment.

Objective: • To characterize the temporal changes of the nerves and vasculature of the bladder in diabetic rats., Materials and Methods: • A total of 36 Sprague-Dawley rats were divided into three groups: streptozotocin-induced diabetics, 5% sucrose-induced diuretics and age-matched controls. • The characteristics of the nerves and vasculature in the equatorial cross-sectional areas of the bladder were examined by immunofluorescence staining of their specific markers, neurofilament 200 (NF200) and CD31, at 1, 9 or 20 weeks after induction. • The distributions of the nerves and blood vessels were observed and the densities were quantified., Results: • Diabetes caused a significant reduction in body weight. Bladder weight increased in diabetic and diuretic rats, but not in controls. • The total cross-sectional wall area and detrusor muscle area at the equatorial midline were greater in bladders of diabetic and diuretic rats than in controls. • Neurofilament 200-immunoreactive (NF200-IR) nerves were mainly distributed in the detrusor muscle. CD31-immunoreactive blood vessels were mainly distributed in the mucosa/submucosa. • There were no significant differences in the NF200-IR nerve terminal area among control, diabetic and diuretic groups. However nerve density was decreased at 9 and 20 weeks in the muscle, and at 20 weeks in the mucosa/submucosa in diabetic and diuretic animals. • Blood vessel density decreased in the diabetic and diuretic groups at 20 weeks in the muscle., Conclusions: • Diabetes induced time-dependent changes in the density of the nerves and vasculature in the bladder tissues. • Diabetes-related polyuria plays an important role in these changes., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Purpose: Urinary diversion has been used as a surgical option for some bladder diseases. We developed a urinary diversion model in the rat and examined the effects of urinary diversion on the bladder., Materials and Methods: We distributed female Sprague-Dawley® rats into age matched control, sham urinary diversion and urinary diversion groups. Each group was subsequently evaluated 1 or 8 weeks after urinary diversion or sham operation. Diversion was done by surgical disconnection of the ureters from the bladder and implantation to the uterine cervix. Conscious cystometry was examined. Bladders were harvested for histological examination and quantification of smooth muscle, urothelium and collagen. Vaginal histology was assessed. Bladder muscarinic and purinergic receptor expression was examined., Results: All rats survived the urinary diversion procedure. Bladder weight decreased in the diversion group. Cystometry showed decreased intercontractile interval and voided volume in the urinary diversion group compared to those in the control and sham operated groups. Compliance was decreased in diverted rats. Smooth muscle and urothelium were decreased as a percent of total bladder cross-sectional area. Collagen increased in 1 and 8-week diverted rats vs controls. Histological examination of the vaginal wall revealed mild swelling in 2 rats. Urinary diversion caused decreased muscarinic 3 and ligand gated purinergic 1 receptor expression but no change in muscarinic 2 or ligand gated purinergic 2 receptors., Conclusions: Creating a urinary diversion model by ureterovaginostomy in the rat is feasible. Urinary diversion causes distinct functional and morphometric bladder alterations., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) belong to a class of small non-coding RNAs that play important roles in complex biological processes through degradation of target mRNAs or repression of their translation. We exploited cross-species comparison to predict miRNAs and identified 266 genes encoding 274 mature miRNAs in Oryctolagus cuniculus. Comparative analyses among mammalian genomes demonstrated that most of the identified miRNAs and their clusters are ancient in origin and conserved among mammals but a few clades as well as some species-specific miRNAs exhibit an ongoing evolutionary process where gain and loss of individual miRNAs have occurred through tandem duplications and random mutations. Our microarray- and RT-PCR-based analyses and target prediction reveal specific expression patterns in brain, spleen, muscle, heart, and ovary, and significant over-representations in certain GO categories as regarded to their mRNA targets include genes that play key roles in signal transduction and transcriptional regulation.

Gasoline engine exhaust has been considered as a major source of air pollution in China. Due to lower cyto- and geno-toxicity effects of methanol engine exhaust, methanol is regarded as a potential substitute for gasoline. We have previously compared cyto- and geno-toxicities of gasoline engine exhaust with that of methanol engine exhaust in A549 cells (Zhang et al., 2007).To characterize the immunotoxic effects for gasoline and methanol engine exhausts in immune cell, in this study, we further compared effects of gasoline and methanol engine exhausts on immune function in RAW264.7 cell and rabbit alveolar macrophages. Results showed that both gasoline and methanol engine exhaust could evidently inhibit RAW264.7 cell proliferation, promote RAW264.7 cell apoptosis, decrease E-rosette formation rate and inhibit anti-tumor effects of alveolar macrophages, at the same time, these effects of gasoline engine exhaust were far stronger than those of methanol engine exhaust. In addition, gasoline engine exhaust could significantly inhibit activities of ADCC of alveolar macrophages, but methanol engine exhaust could not. These results suggested that both gasoline and methanol engine exhausts might be immunotoxic atmospheric pollutants, but some effects of gasoline engine exhaust on immunotoxicities may be far stronger than that of methanol engine exhaust., (Copyright 2010 Elsevier Ltd. All rights reserved.)