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Bacillus subtilis relies on biofilms for survival in harsh environments. Extracellular polymeric substance (EPS) is a crucial component of biofilms, yet the dynamics of EPS production in single cells remain elusive. To unveil the modulation of EPS synthesis, we built a minimal network model comprising the SinI-SinR-SlrR module, Spo0A, and EPS. Stochastic simulations revealed that antagonistic interplay between SinI and SinR enables EPS production in bursts. SlrR widens these bursts and increases their frequency by stabilizing SinR-SlrR complexes and depleting free SinR. DNA replication and chromosomal positioning of key genes dictate pulsatile changes in the slrR:sinR gene dosage ratio (gr) and Spo0A-P levels, each promoting EPS production in distinct phases of the cell cycle. As the cell cycle lengthens with nutrient stress, the duty cycle of gr pulsing decreases, whereas the amplitude of Spo0A-P pulses elevates. This coordinated response facilitates keeping a constant proportion of EPS-secreting cells within colonies across diverse nutrient conditions. Our results suggest that bacteria may 'encode' eps expression through strategic chromosomal organization. This work illuminates how stochastic protein interactions, gene copy number imbalance, and cell-cycle dynamics orchestrate EPS synthesis, offering a deeper understanding of biofilm formation.
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Bacillus subtilis , Proteínas Bacterianas , Biopelículas , Replicación del ADN , Regulación Bacteriana de la Expresión Génica , Biopelículas/crecimiento & desarrollo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Bacillus subtilis/fisiología , Replicación del ADN/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Matriz Extracelular de Sustancias Poliméricas/metabolismo , Ciclo Celular/genéticaRESUMEN
PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.
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Hemorreoidectomía , Hemorroides , Terapia por Láser , Humanos , Hemorroides/cirugía , Masculino , Ligadura/métodos , Femenino , Persona de Mediana Edad , Hemorreoidectomía/métodos , Adulto , Terapia por Láser/métodos , Resultado del Tratamiento , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , RecurrenciaRESUMEN
The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-ß-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-ß-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-ß-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.
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Oro , Imagen por Resonancia Magnética , Glicosilación , Tecnología , Espectroscopía de Resonancia MagnéticaRESUMEN
It is widely known that integrative and conjugative elements (ICEs) play an important role in the transmission of resistance genes and other exogenous genes. The present study aimed to characterize the three novel ICEs including ICEGpa76, ICEGpa44, and ICEGpa11, from Glaesserella parasuis. The ICEs from G. parasuis strains d76, Z44, and XP11 were predicted and identified by whole-genome sequencing (WGS) analysis, ICEfinder, and PCR. Characterization of G. parasuis strains carrying ICEs were determined by conjugation assay, antimicrobial susceptibility testing, WGS, phylogenetic analysis, and comparative sequence analysis.The WGS results showed that three ICEs from G. parasuis have a common genetic backbone belonging to characteristics ofthe ICEHpa1 family. The sequence comparison showed that the ICEHpa1 family has five hot spots (HSs) determined by IS6, IS110, and IS256. Moreover, two variable regions (VRs), VR1 and VR2 were determined by multidrug resistance genes and the rearrangement hotspot (rhs) family, respectively. VR1 consists of multidrug resistance genes, ISApl1s, and other accessory genes, while VR2 is composed of IS4, rhs family, transposase, and hypothetical protein genes. Conjugation experiments and MICs revealed that three ICEs could be transferred to G. parasuis strain IV52, indicating these three ICEs could be transmitted horizontally among G. parasuis strains. Additionally, the difference in resistance genes from ICEs might be due to the insertion function of the ISApl1s in VR1, and the rhs family in VR2 might evolve andthen be stably inherited in G. parasuis. These results further elucidated the transmission mechanism of exogenous genes in G. parasuis.
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Conjugación Genética , Genes MDR , Animales , FilogeniaRESUMEN
Artificial intelligence (AI) approaches in cancer analysis typically utilize a 'one-size-fits-all' methodology characterizing average patient responses. This manner neglects the diverse conditions in the pancancer and cancer subtypes of individual patients, resulting in suboptimal outcomes in diagnosis and treatment. To overcome this limitation, we shift from a blanket application of statistics to a focus on the explicit recognition of patient-specific abnormalities. Our objective is to use multiomics data to empower clinicians with personalized molecular descriptions that allow for customized diagnosis and interventions. Here, we propose a highly trustworthy multiomics learning (HTML) framework that employs multiomics self-adaptive dynamic learning to process each sample with data-dependent architectures and computational flows, ensuring personalized and trustworthy patient-centering of cancer diagnosis and prognosis. Extensive testing on a 33-type pancancer dataset and 12 cancer subtype datasets underscored the superior performance of HTML compared with static-architecture-based methods. Our findings also highlighting the potential of HTML in elucidating complex biological pathogenesis and paving the way for improved patient-specific care in cancer treatment.
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Inteligencia Artificial , Neoplasias , Humanos , Multiómica , Neoplasias/diagnóstico , Neoplasias/genética , AprendizajeRESUMEN
OBJECTIVES: The aim of this study was to characterize the floR-carrying plasmids originating from Glaesserella parasuis and Actinobacillus indolicus isolated from pigs with respiratory disease in China. METHODS: A total of 125 G. parasuis and 28 A. indolicus strains collected between 2009 and 2022 were screened for florfenicol resistance. Characterization of floR-positive isolates and plasmids were determined by antimicrobial susceptibility testing, serotyping, multilocus sequence typing (MLST), conjugation and transformation assays, whole-genome sequencing (WGS), and phylogenetic analysis. RESULTS: One A. indolicus and six G. parasuis were identified as positive for floR. The six G. parasuis were assigned to four different serovars, including serovars 6, 7, 9, and unknown. In addition to strain XP11, six floR genes were located on plasmids. The six floR-bearing plasmids could be transformed into Pasteurella multocida and divided into two different types, including â¼5000 bp and â¼6000 bp plasmids. The â¼5000 bp plasmids consisting of rep, lysR, mobB, and floR genes, exhibited high similarity among Pasteurellaceae bacteria. Furthermore, the â¼6000 bp plasmids, consisting of rep, lysR, mobC, mobA/L, and floR genes, showed high similarity between G. parasuis and Actinobacillus Spp. Notably, WGS results showed that the floR modules of the two types of plasmids could be transferred and integrated into the diverse Pasteurellaceae- origined plasmids. CONCLUSION: This study firstly reported the characterization of floR-carrying plasmids from A. indolicus and a non-virulent serovar of G. parasuis in pigs in China and elucidated the transmission mechanism of the floR resistance gene among the Pasteurellaceae family.
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Actinobacillus , Antibacterianos , Animales , Porcinos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Tipificación de Secuencias Multilocus , Filogenia , Plásmidos/genética , Actinobacillus/genéticaRESUMEN
Arsenic is an essential dopant in conventional silicon-based semiconductors and emerging phase-change memory (PCM), yet the detailed functional mechanism is still lacking in the latter. Here, we fabricate chalcogenide-based ovonic threshold switching (OTS) selectors, which are key units for suppressing sneak currents in 3D PCM arrays, with various As concentrations. We discovered that incorporation of As into GeS brings >100 °C increase in crystallization temperature, remarkably improving the switching repeatability and prolonging the device lifetime. These benefits arise from strengthened As-S bonds and sluggish atomic migration after As incorporation, which reduces the leakage current by more than an order of magnitude and significantly suppresses the operational voltage drift, ultimately enabling a back-end-of-line-compatible OTS selector with >12 MA/cm2 on-current, ~10 ns speed, and a lifetime approaching 1010 cycles after 450 °C annealing. These findings allow the precise performance control of GeSAs-based OTS materials for high-density 3D PCM applications.
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Porcine sapelovirus (PSV) is a ubiquitous virus in farmed pigs that is associated with SMEDI syndrome, polioencephalomyelitis, and diarrhea. However, there are few reports on the prevalence and molecular characterization of PSV in Fujian Province, Southern China. In this study, the prevalence of PSV and a poetical combinative strain PSV2020 were characterized using real-time PCR, sequencing, and bioinformatics analysis. As a result, an overall sample prevalence of 30.8% was detected in 260 fecal samples, and a farm prevalence of 76.7% was observed in 30 Fujian pig farms, from 2020 to 2022. Noteably, a high rate of PSV was found in sucking pigs. Bioinformatics analysis showed that the full-length genome of PSV2020 was 7550 bp, and the genetic evolution of its ORF region was closest to the G1 subgroup, which was isolated from Asia and America; the similarity of nucleotides and amino acids to other PSVs was 59.5~88.7% and 51.7~97.0%, respectively. However, VP1 genetic evolution analysis showed a distinct phylogenetic topology from the ORF region; PSV2020 VP1 was closer to the DIAPD5469-10 strain isolated from Italy than strains isolated from Asia and America, which comprise the G1 subgroup based on the ORF region. Amino acid discrepancy analysis illustrated that the PSV2020 VP1 gene inserted twelve additional nucleotides, corresponding to four additional amino acids (STAE) at positions 898-902 AAs. Moreover, a potential recombination signal was observed in the 2A coding region, near the 3' end of VP1, owing to recombination analysis. Additionally, 3D genetic evolutionary analysis showed that all reference strains demonstrated, to some degree, regional conservation. These results suggested that PSV was highly prevalent in Fujian pig farms, and PSV2020, a PSV-1 genotype strain, showed gene diversity and recombination in evolutionary progress. This study also laid a scientific foundation for the investigation of PSV epidemiology, molecular genetic characteristics, and vaccine development.
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Aminoácidos , Enterovirus Porcinos , Porcinos , Animales , Prevalencia , Granjas , Filogenia , China/epidemiología , Variación Genética , Recombinación GenéticaRESUMEN
Conjugative plasmids play a vital role in bacterial evolution and promote the spread of antibiotic resistance. They usually cause fitness costs that diminish the growth rates of the host bacteria. Compensatory mutations are known as an effective evolutionary solution to reduce the fitness cost and improve plasmid persistence. However, whether the plasmid transmission by conjugation is sufficient to improve plasmid persistence is debated since it is an inherently costly process. Here, we experimentally evolved an unstable and costly mcr-1 plasmid pHNSHP24 under laboratory conditions and assessed the effects of plasmid cost and transmission on the plasmid maintenance by the plasmid population dynamics model and a plasmid invasion experiment designed to measure the plasmid's ability to invade a plasmid-free bacterial population. The persistence of pHNSHP24 improved after 36 days evolution due to the plasmid-borne mutation A51G in the 5'UTR of gene traJ. This mutation largely increased the infectious transmission of the evolved plasmid, presumably by impairing the inhibitory effect of FinP on the expression of traJ. We showed that increased conjugation rate of the evolved plasmid could compensate for the plasmid loss. Furthermore, we determined that the evolved high transmissibility had little effect on the mcr-1-deficient ancestral plasmid, implying that high conjugation transfer is vital for maintaining the mcr-1-bearing plasmid. Altogether, our findings emphasized that, besides compensatory evolution that reduces fitness costs, the evolution of infectious transmission can improve the persistence of antibiotic-resistant plasmids, indicating that inhibition of the conjugation process could be useful to combat the spread of antibiotic-resistant plasmids. IMPORTANCE Conjugative plasmids play a key role in the spread of antibiotic resistance, and they are well-adapted to the host bacteria. However, the evolutionary adaptation of plasmid-bacteria associations is not well understood. In this study, we experimentally evolved an unstable colistin resistance (mcr-1) plasmid under laboratory conditions and found that increased conjugation rate was crucial for the persistence of this plasmid. Interestingly, the evolved conjugation was caused by a single-base mutation, which could rescue the unstable plasmid from extinction in bacterial populations. Our findings imply that inhibition of the conjugation process could be necessary for combating the persistence of antibiotic-resistance plasmids.
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Antibacterianos , Bacterias , Plásmidos/genética , Farmacorresistencia Microbiana/genética , Bacterias/genética , Mutación , Antibacterianos/farmacologíaRESUMEN
This study aimed to characterize two novel mcr-1 variants, mcr-1.35 and mcr-1.36, which originated from Moraxella spp. that were isolated from diseased pigs in China. The Moraxella spp. carrying novel mcr-1 variants were subjected to whole-genome sequencing (WGS) and phylogenetic analysis based on the 16S rRNA gene. The mcr-1 variants mcr-1.35 and mcr-1.36 were characterized using phylogenetic analysis, a comparison of genetic environments, and protein structure prediction. The WGS indicated that two novel mcr-1 variants were located in the chromosomes of three Moraxella spp. with a genetic environment of mcr-1-pap2. In addition to the novel colistin resistance genes mcr-1.35 and mcr-1.36, the three Moraxella spp. contained other antimicrobial resistance genes, including aac(3)-IId, tet(O), sul2, floR, and blaROB-3. A functional cloning assay indicated that either the mcr-1.35 or mcr-1.36 gene could confer resistance to colistin in Escherichia coli DH5α and JM109. The nucleotide sequences of mcr-1.35 and mcr-1.36 presented 95.33 and 95.33% identities, respectively, to mcr-1.1. The phylogenetic analysis showed that mcr-1.35 and mcr-1.36 were derived from Moraxella spp. that belonged to subclades that were different from those of the mcr-1 variants (mcr-1.1 to mcr-1.34 except mcr-1.10) originating from Enterobacteriaceae. The deduced amino acid sequences of MCR-1.35 (MCR-1.36) showed 96.67% (96.49%), 82.59% (82.04%), 84.07% (83.52%), 55.52% (55.17%), 59.75% (59.57%), and 61.88% (61.69%) identity to MCR-1.10, MCR-2.2, MCR-6.1, MCR-LIN, MCR-OSL, and MCR-POR, respectively, that originated from Moraxella sp. Notably, protein structure alignment showed only a few changes in amino acid residues between MCR-1.1 and MCR-1.35, as well as between MCR-1.1 and MCR-1.36. In conclusion, this study identified Moraxella spp. carrying two novel mcr-1 variants, mcr-1.35 and mcr-1.36, conferring resistance to colistin, which were isolated from pig farms in China. In addition, mcr-like variants were observed to be located in the chromosomes of some species of Moraxella isolated from pig samples.
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The selector is an indispensable section of the phase change memory (PCM) chip, where it not only suppresses the crosstalk, but also provides high on-current to melt the incorporated phase change material. In fact, the ovonic threshold switching (OTS) selector is utilized in 3D stacking PCM chips by virtue of its high scalability and driving capability. In this paper, the influence of Si concentration on the electrical properties of Si-Te OTS materials is studied; the threshold voltage and leakage current remain basically unchanged with the decrease in electrode diameter. Meanwhile, the on-current density (Jon) increases significantly as the device is scaling down, and 25 MA/cm2 on-current density is achieved in the 60-nm SiTe device. In addition, we also determine the state of the Si-Te OTS layer and preliminarily obtain the approximate band structure, from which we infer that the conduction mechanism conforms to the Poole-Frenkel (PF) model.
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Purpose: The objective of this study was to elucidate the characteristics and mechanism of formation of the fusion plasmid pHNSHP24 carrying mcr-1.1. Materials and Methods: mcr-1.1-bearing Escherichia coli SHP24 and the corresponding transconjugant were subjected to whole-genome sequencing (WGS) combining the Illumina and MinION platforms to obtain the complete sequences of the fusion plasmid and its original plasmids. Results: Complete sequence analysis and S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) results indicated that E. coli SHP24 carried four plasmids: mcr-1.1-harboring phage-like plasmid pHNSHP24-3, F53:A-:B- plasmid pHNSHP24-4, pHNSHP24-1, and pHNSHP24-2. However, the plasmid pHNSHP24 carrying mcr-1.1 presents in the transconjugant differed from the four plasmids in the donor strain SHP24. Further analysis showed that pHNSHP24 may be the fusion product of pHNSHP24-3 and pHNSHP24-4 and is formed through a replicative transposition mechanism mediated by IS26 in E. coli SHP24. Conclusion: This study is the first to report the fusion of an mcr-1.1-harboring phage-like pO111 plasmid and an F53:A-:B- plasmid mediated by IS26. Our findings revealed the role of phage-like and fusion plasmids in the dissemination of mcr-1.1.
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INTRODUCTION: Rapid dissemination of plasmid-borne polymyxin resistance mcr-1 genes threatens the efficacy of polymyxins. Acquisition of mcr-1 imposes a fitness cost on bacteria; identifying the molecular mechanisms underpinning this fitness cost will help in the development of adjunctive antimicrobial therapies that target polymyxin-resistant Gram-negative pathogens. METHODS: Phenotypic assays and transcriptomics were acquired to investigate the impact of mcr-1 expression on membrane characteristics and transcriptomic responses in Escherichia coli TOP10 carrying the empty vector pBAD (TOP10+pBAD) and harbouring pBAD-mcr-1 (TOP10+pBAD-mcr-1). RESULTS: The overexpression of mcr-1 increased outer membrane permeability and caused membrane depolarisation, reflective of the transcriptomic results that showed downregulation of multiple genes involved in lipopolysaccharide core and O-antigen biosynthesis. Overexpression of mcr-1 also caused considerable gene expression changes in pathways involving carbohydrate metabolism (phosphotransferase system, pentose phosphate pathway, and pantothenate and coenzyme A biosynthesis), ABC transporters and intracellular responses to stress, especially those associated with oxidative and nucleic acid damage. Expression of mcr-1 also triggered the production of reactive oxygen species. CONCLUSION: These findings indicate that overexpression of mcr-1 results in persistent transcriptomic changes that primarily involve disruption to cell envelope synthesis via the reduction of LPS modifications, as well as dysregulation of carbon metabolism, redox balance and nucleic acids. These consequences of expression dysregulation may act as the main factors that impose a fitness cost with mcr-1 expression.
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Proteínas de Escherichia coli , Ácidos Nucleicos , Antibacterianos/farmacología , Carbono , Colistina/metabolismo , Colistina/farmacología , Farmacorresistencia Bacteriana/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Pruebas de Sensibilidad Microbiana , Ácidos Nucleicos/metabolismo , Oxidación-Reducción , Plásmidos , PolimixinasRESUMEN
During the past decade, falling has been one of the top three causes of death amongst firefighters in China. Even though there are many studies on fall-detection systems (FDSs), the majority use a single motion sensor. Furthermore, few existing studies have considered the impact sensor placement and positioning have on fall-detection performance; most are targeted toward fall detection of the elderly. Unfortunately, floor cracks and unstable building structures in the fireground increase the difficulty of detecting the fall of a firefighter. In particular, the movement activities of firefighters are more varied; hence, distinguishing fall-like activities from actual falls is a significant challenge. This study proposed a smart wearable FDS for firefighter fall detection by integrating motion sensors into the firefighter's personal protective clothing on the chest, elbows, wrists, thighs, and ankles. The firefighter's fall activities are detected by the proposed multisensory recurrent neural network, and the performances of different combinations of inertial measurement units (IMUs) on different body parts were also investigated. The results indicated that the sensor fusion of IMUs from all five proposed body parts achieved performances of 94.10%, 92.25%, and 94.59% in accuracy, sensitivity, and specificity, respectively.
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Accidentes por Caídas , Dispositivos Electrónicos Vestibles , Anciano , Humanos , Movimiento (Física) , Redes Neurales de la Computación , MuñecaRESUMEN
Organic thin film transistors (OTFTs) are a promising technology for the application of photosensors in smart wearable devices. Light-induced electrical behavior of OTFTs is explored to achieve diverse functional requirements. In most studies, OTFTs show an increased drain current (ID) under light irradiation. Here, we use an ultraviolet (UV) light absorption top layer, tris(8-hydroxyquinoline) aluminum (Alq3), to improve the UV light response of poly(3-hexylthiophene-2,5-diyl) (P3HT)-based OTFTs. Unexpectedly, the Alq3-covered device operated at the accumulation mode demonstrates a decreased ID during the UV light irradiation. N,N'-Ditridecyl-3,4,9,10-perylene tetracarboxylic diimide (PTCDI, electron acceptor), pentacene (electron donor), and lithium fluoride (LiF, insulator) as an interlayer were inserted between the P3HT and the Alq3 layers. The PTCDI/Alq3-covered device also shows an unusual decrease in ID under the UV light but an increase in ID under the green light. The pentacene/Alq3-covered device shows an increased ID during the UV light irradiation and, unexpectedly, a memory effect in ID after removing the UV light. The LiF/Alq3-covered device exhibits an electrical behavior similar to the bare P3HT-based device under the UV light. Results of spectroscopic analyses and theoretical calculations have shown that the occurrence of charge transfer at heterojunctions during the UV light irradiation causes charge modulation in the multilayered P3HT-based OTFTs and then results in an unusual decrease or memory effect in ID. In addition, the unexpected ID reduction can be observed in the Alq3-covered poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene]-based OTFTs under UV light. The features, including opposite electrical responses to different wavelengths of light and optical memory effect, provide the multilayered P3HT-based OTFTs with potential for various optical applications, such as image recognition devices, optical logic gates, light dosimeters, and optical synapses.
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Defective autophagy occurred in osteoblasts under stress induced by high glucose and played an essential role in the development of diabetic osteoporosis. Timosaponin BII, a steroidal saponin isolated from the rhizomes of Anemarrhena asphodeloides Bunge, possessed anti-osteoporosis properties. In this study, we investigated the efficacy and mechanism of timosaponin BII on diabetic osteoporosis. Timosaponin BII attenuated the deterioration in the microarchitecture of the tibias in diabetic rats. Furthermore, treatment with timosaponin BII dose-dependently reduced hyperglycemia-induced cell apoptosis in primary osteoblasts from rat calvaria. High glucose-exposed osteoblasts exhibited increased mitochondrial superoxide level, decreased mitochondrial membrane potential and impaired autophagic flux, which was attenuated by timosaponin BII, as evidenced by the upregulation of autophagosome numbers, LC3B puncta formation and Beclin1 expression. The antiapoptotic and antioxidative effect of timosaponin BII were repressed by the autophagy inhibitor 3-methyladenine and enhanced by the autophagy inducer rapamycin. Further studies showed that timosaponin BII suppressed the phosphorylation of mTOR and S6K, as well as the downstream factors NFκB and IκB, consequently activating autophagy and decreasing apoptosis. Of note, coincubation of timosaponin BII with MHY1485, a pharmacological activator of mTOR, diminished the protein expression of Bcl2 induced by timosaponin BII, which was in parallel with decreased autophagy and increased phosphorylation of NFκB and IκB. Overexpression of NFκB reduced timosaponin BII-evoked autophagy and promoted apoptosis. The in vivo results showed that oral administration of timosaponin BII downregulated the phosphorylation of mTOR and NFκB and upregulated Beclin1 expression in the proximal tibias of diabetic rats. These results suggested that timosaponin BII attenuated high glucose-induced oxidative stress and apoptosis through activating autophagy by inhibiting mTOR/NFκB signalling in osteoblasts.
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Diabetes Mellitus Experimental , Hiperglucemia , Osteoporosis , Saponinas , Animales , Apoptosis , Autofagia , Diabetes Mellitus Experimental/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Osteoblastos , Osteoporosis/tratamiento farmacológico , Ratas , Saponinas/farmacología , Transducción de Señal , Esteroides/farmacología , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Plasmid-mediated colistin resistance gene mcr-1 generally confers low-level resistance. The purpose of this study was to investigate the impact of mcr-1 on the development of high-level colistin resistance (HLCR) in Klebsiella pneumoniae and Escherichia coli. In this study, mcr-1-negative K. pneumoniae and E. coli strains and their corresponding mcr-1-positive transformants were used to generate HLCR mutants via multiple passages in the presence of increasing concentrations of colistin. We found that for K. pneumoniae, HLCR mutants with minimum inhibitory concentrations (MICs) of colistin from 64 to 1,024 mg/L were generated. Colistin MICs increased 256- to 4,096-fold for mcr-1-negative K. pneumoniae strains but only 16- to 256-fold for the mcr-1-harboring transformants. For E. coli, colistin MICs increased 4- to 64-folds, but only 2- to 16-fold for their mcr-1-harboring transformants. Notably, mcr-1 improved the survival rates of both E. coli and K. pneumoniae strains when challenged with relatively high concentrations of colistin. In HLCR K. pneumoniae mutants, amino acid alterations predominately occurred in crrB, followed by phoQ, crrA, pmrB, mgrB, and phoP, while in E. coli mutants, genetic alterations were mostly occurred in pmrB and phoQ. Additionally, growth rate analyses showed that the coexistence of mcr-1 and chromosomal mutations imposed a fitness burden on HLCR mutants of K. pneumoniae. In conclusion, HLCR was more likely to occur in K. pneumoniae strains than E. coli strains when exposed to colistin. The mcr-1 gene could improve the survival rates of strains of both bacterial species but could not facilitate the evolution of high-level colistin resistance.
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The design of low-cost yet highly efficient electrocatalysts plays a critical role in energy storage and conversion reactions. The oxygen evolution reaction (OER) is considered a bottleneck of electrochemical water splitting for hydrogen fuel generation. It is still challenging to extract a high density of charge carriers in noble-metal-free alternative catalysts to facilitate sluggish kinetics. Herein, we report the rational design and coherent interface engineering for combining light-harvesting Cu31S16 with electroactive Co9-xNixS8 (x = 0-9) to form novel Cu31S16-Co9-xNixS8 heterodimers. By delicately controlling the kinetic growth in a seed-mediated growth method, the bifunctional centers, even with two distinct crystal phases, were integrated into a synergistic architecture, which achieved full-spectrum solar energy capture and light conversion to drive and activate the electrochemical reaction. Benefiting from the well-defined structure, high-quality interface, oriented attachment, and optimal Co/Ni bimetal ratio, Cu31S16-Co7.2Ni1.8S8 produces a dramatically reduced overpotential (242 mV at 10 mA cm-2) with a shift of 83 mV under visible-light excitation, achieving a 4.5-fold higher turnover frequency than that of its unirradiated Co7.2Ni1.8S8 counterpart. This enhanced performance also far exceeds commercial RuO2 (358 mV at 10 mA cm-2) and most nonprecious-metal nanocatalysts. Further mechanistic studies reveal that coherent interface engineering leads to a strong photo/electricity coupling effect and efficient spatial charge separation, which induces sufficient hot holes that eventually accumulate at the electroactive sites to accelerate the multihole-involved OER. This work would open up new opportunities for the fabrication of non-noble metal electrocatalysts and management of charge carriers.
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Cyperus rotundus L. (C. rotundus) is a sedge belonging to the family Cyperaceae and is widely distributed in tropical and warmer temperate regions worldwide. It is one of the oldest traditional medicinal herbs in China, India, Japan, and Korea. In this study, we sequenced the complete chloroplast genome of C. rotundus on the Illumina HiSeq Platform. The chloroplast genome is 182,986 bp in length, with a typical quadripartite structure and consisting of a pair of inverted repeat (IR) regions (35,969 bp) separated by a large single-copy (LSC) region (100,733 bp) and a small single-copy (SSC) region (10,315 bp). It was predicted to contain a total of 133 genes, with an overall GC content of 33.26%. Phylogenetic analysis suggested C. rotundus is sister to Eleocharis celluosa and Eleocharis dulcis.
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BACKGROUND: Traditional rubber band ligation can improve the symptoms of hemorrhoids, the techniques used vary among centers and the degree of hemorrhoids may also affect the therapeutic efficacy and postoperative outcome, especially for patients with grade III hemorrhoids (hemorrhoid prolapses). This study aimed to investigate the clinical efficacy of modified rubber band ligation (MRBL) in the treatment of grade III internal hemorrhoids. METHODS: A total of 120 patients with grade III internal hemorrhoids were randomly assigned to receive MRBL or Milligan-Morgan haemorrhoidectomy (MMH) (n=60 per group). The post-operative pain, bleeding, urine retention and feeling of anal distension were recorded, and the resting anal pressure (RAP) and post-operative recurrence rate were compared between two groups. RESULTS: The post-operative pain, bleeding and urine retention in the MRBL group were improved significantly as compared with the MMH group (P<0.05), but the feeling of anal distension was similar between them (P>0.05). The RAP remained unchanged after MRBL, but the RAP at 1 month after surgery in the MMH group increased markedly (P<0.01) as compared with that before surgery and was significantly higher than that in the MRBL group (P<0.01). The post-operative recurrence rate was comparable between two groups (P>0.05). CONCLUSIONS: As compared with traditional MMH, MRBL is effective to attenuate the post-operative pain and other discomforts and stabilize the RA. Thus, MRBL is an ideal choice for the treatment of grade III internal hemorrhoids.