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Dynamic molecular devices operating with time- and history-dependent performance raised new challenges for the fundamental study of microscopic non-steady-state charge transport as well as functionalities that are not achievable by steady-state devices. In this study, we reported a generic dynamic mode of molecular devices by addressing the transient redox state of ubiquitous quinone molecules in the junction by proton/water transfer. The diffusion limited slow proton/water transfer-modulated fast electron transport, leading to a non-steady-state transport process, as manifested by the negative differential resistance, dynamic hysteresis, and memory-like behavior. A quantitative paradigm for the study of the non-steady-state charge transport kinetics was further developed by combining the theoretical model and transient state characterization, and the principle of the dynamic device can be revealed by the numerical simulator. On applying pulse stimulation, the dynamic device emulated the neuron synaptic response with frequency-dependent depression and facilitation, implying a great potential for future nonlinear and brain-inspired devices.
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Ovule initiation determines the maximum ovule number and has great impact on seed number and yield. However, the regulation of ovule initiation remains largely elusive. We previously reported that most of the ovule primordia initiate asynchronously at floral stage 9 and PINFORMED1 (PIN1) polarization and auxin distribution contributed to this process. Here, we further demonstrate that a small amount of ovule primordia initiate at floral stage 10 when the existing ovules initiated at floral stage 9 start to differentiate. Genetic analysis revealed that the absence of PIN3 function leads to the reduction in pistil size and the lack of late-initiated ovules, suggesting PIN3 promotes the late ovule initiation process and pistil growth. Physiological analysis illustrated that, unlike picloram, exogenous application of NAA can't restore these defective phenotypes, implying that PIN3-mediated polar auxin transport is required for the late ovule initiation and pistil length. qRT-PCR results indicated that the expression of SEEDSTICK (STK) is up-regulated under auxin analogues treatment while is down-regulated in pin3 mutants. Meanwhile, overexpressing STK rescues pin3 phenotypes, suggesting STK participates in PIN3-mediated late ovule initiation possibly by promoting pistil growth. Furthermore, brassinosteroid influences the late ovule initiation through positively regulating PIN3 expression. Collectively, this study demonstrates that PIN3 promotes the late ovule initiation and contributes to the extra ovule number. Our results give important clues for increasing seed number and yield of cruciferous and leguminous crops.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Proteínas de Dominio MADS/genética , Óvulo Vegetal/genéticaRESUMEN
Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.
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Colorantes Fluorescentes , Tirosina 3-Monooxigenasa , Pez Cebra , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Tirosina 3-Monooxigenasa/metabolismo , Tirosina 3-Monooxigenasa/análisis , Animales , Ratones , Humanos , Imagen Óptica , Línea Celular Tumoral , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismoRESUMEN
Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.
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Inmunoconjugados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Resistencia a Antineoplásicos , Terapia Molecular Dirigida/métodos , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
INTRODUCTION AND HYPOTHESIS: Identifying the factors influencing the development of female urinary incontinence (UI) may facilitate early intervention, potentially delaying its progression. This study was aimed at investigating the impact of lifestyle habits on the severity of UI among women in East China. METHODS: This study included 414 women from six communities in East China who reported symptoms of UI and was conducted between September and December 2020. Data were collected using a general information questionnaire, the Toileting Behaviours: Women's Elimination Behaviours scale, and the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form Chinese Version. Participants were categorised into two groups: those with mild UI and those with moderate-to-severe UI. Propensity-score matching was performed to balance confounding factors, and logistic regression was used to explore the relationship between lifestyle behaviours and UI severity. RESULTS: A total of 117 pairs were successfully matched. Logistic regression analysis revealed that daily perineal cleaning significantly protected against moderate-to-severe UI (p < 0.05). Conversely, living alone, poor sleep quality and hovering over the toilet while voiding were identified as independent risk factors for moderate-to-severe UI (p < 0.05). CONCLUSION: Several lifestyle habits significantly impact the severity of UI among adult women. Screening for mild urinary leakage symptoms and implementing timely interventions are crucial for preventing the aggravation of UI and improving ability to work and quality of life.
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Estilo de Vida , Índice de Severidad de la Enfermedad , Incontinencia Urinaria , Humanos , Femenino , China/epidemiología , Estudios Transversales , Incontinencia Urinaria/epidemiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Encuestas y Cuestionarios , AncianoRESUMEN
High electrical conductivity and super high hardness are two sought-after material properties, but both are contradictory because the effective suppression of dislocation movement generally increases the scattering of conducting electrons. Here we synthesized a high-entropy dodecaboride composite (HEDC) with a large number of atomic-scale interlocking layers. It shows a Vickers hardness of 51.2 ± 3.6 GPa under an applied load of 0.49 N and an electrical resistivity of 44.5 µΩ·cm at room temperature. Such HEDC achieves superhardness by inheriting the high intrinsic hardness of its constituent phases and restricting the dislocation motion to further enhance the extrinsic hardness through forming numerous atom-scale interlocks between different slip systems. Moreover, the HEDC maintains the excellent electrical conductivity of the constituent borides, and the competition between two correlating structures produces the special kind of coherent boundary that minimizes the scattering of conducting electrons and does not largely deteriorate the electrical conductivity.
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Elevated stress levels are related to diminished mental health, potentially leading to decreased well-being and performance of nursing students. While researchers have focused on developing stress management interventions, there is a need to synthesize the evidence. A systematic review with meta-analysis was conducted to assess the evidence for the effectiveness of stress management interventions in nursing students. A systematic literature search identified controlled stress management interventions employing a validated psychological or physiological stress measure. Forty-one studies were included, with 36 forming a pool of 2715 participants in the meta-analysis. The overall effect on psychological stress was positive. Intervention type, delivery modality, intervention duration in weeks, and number of sessions were moderators of intervention effectiveness, with more significant effects for mind-body programs, on-site delivery methods, durations of 9-12 weeks, and 15-30 sessions. For physiological stress, the biomarkers of blood pressure, heart rate, and cortisol levels decreased significantly. Future research is necessary for promising outcomes related to currently underrepresented indicators and to investigate the long-term effects of interventions.
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Estrés Psicológico , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Estrés Psicológico/psicologíaRESUMEN
The mildly thermophilic purple phototrophic bacterium Allochromatium tepidum provides a unique model for investigating various intermediate phenotypes observed between those of thermophilic and mesophilic counterparts. The core light-harvesting (LH1) complex from A. tepidum exhibits an absorption maximum at 890 nm and mildly enhanced thermostability, both of which are Ca2+-dependent. However, it is unknown what structural determinants might contribute to these properties. Here, we present a cryo-EM structure of the reaction center-associated LH1 complex at 2.81 Å resolution, in which we identify multiple pigment-binding α- and ß-polypeptides within an LH1 ring. Of the 16 α-polypeptides, we show that six (α1) bind Ca2+ along with ß1- or ß3-polypeptides to form the Ca2+-binding sites. This structure differs from that of fully Ca2+-bound LH1 from Thermochromatium tepidum, enabling determination of the minimum structural requirements for Ca2+-binding. We also identified three amino acids (Trp44, Asp47, and Ile49) in the C-terminal region of the A. tepidum α1-polypeptide that ligate each Ca ion, forming a Ca2+-binding WxxDxI motif that is conserved in all Ca2+-bound LH1 α-polypeptides from other species with reported structures. The partial Ca2+-bound structure further explains the unusual phenotypic properties observed for this bacterium in terms of its Ca2+-requirements for thermostability, spectroscopy, and phototrophic growth, and supports the hypothesis that A. tepidum may represent a "transitional" species between mesophilic and thermophilic purple sulfur bacteria. The characteristic arrangement of multiple αß-polypeptides also suggests a mechanism of molecular recognition in the expression and/or assembly of the LH1 complex that could be regulated through interactions with reaction center subunits.
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Chromatiaceae , Complejos de Proteína Captadores de Luz , Proteínas Bacterianas/metabolismo , Sitios de Unión , Calcio/metabolismo , Complejos de Proteína Captadores de Luz/química , Péptidos/químicaRESUMEN
Currently, the genus Paracoccus comprises 76 recognized species. Members of Paracoccus are mostly isolated from environmental, animal, and plant sources. This report describes and proposes a novel species of Paracoccus isolated from clinical specimens of the human ocular surface. We isolated two aerobic, Gram-stain-negative, non-spore-forming, coccoid or short rod-shaped, and non-motile strains (designated DK398T and DK608) from conjunctival sac swabs of two healthy volunteers. The results showed that the strains grew best under the conditions of 28°C, pH 7.0, and 1.0â% (w/v) NaCl. Sequence analysis based on the 16S rRNA gene showed that strains DK398T and DK608 were members of Paracoccus, most similar to Paracoccus laeviglucosivorans 43PT (98.54 and 98.62â%), Paracoccus litorisediminis GHD-05T (98.34 and 98.41â%), and Paracoccus limmosus NB88T (98.21 and 98.29â%). Phenotypic analysis showed that DK398T and DK608 were positive for catalase and oxidase, negative for producing N-acetyl-ß-glucosaminic acid, arginine dihydrolase, and ß-glucuronidase but positive for leucine arylamidase. The predominant isoprenoid quinone was Q-10, and the major polar lipids included phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and an unidentified glycolipid. The major fatty acids (>10%) were summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c) and C16â:â0. The meso-diaminopimelic acid was found in the cell wall peptidoglycan of DK398T. The major cell wall sugars were ribose and galactose. Based on the results of phylogenetic analyses, low (<83.22â%) average nucleotide identity, digital DNA-DNA hybridization (<26.0%), chemotaxonomic analysis, and physiological properties, strain DK398T represents a novel species of the genus Paracoccus, for which the name Paracoccus shanxieyensis sp. nov. is proposed. The type strain is DK398T (=CGMCC 1.17227T=JCM 33719T).
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Ácidos Grasos , Paracoccus , Animales , Humanos , Ácidos Grasos/química , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Ubiquinona/química , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Composición de BaseRESUMEN
With the widespread use of sulfonamide antibiotics (SAs), SAs are detected as residues in aquatic environments, posing a serious threat to human life and safety. Because of their high water solubility, fast transmission rate, and strong antibacterial properties, the safe disposal of SAs has become a key constraint for water quality assurance. Therefore, an ultrasound (US)-assisted zero-valent iron (ZVI)/persulfate (PS) system was proposed to explore the rapid and effective degradation of SAs. Comparative experiments were performed to study the removal of sulfadiazine (SDZ) by US, ZVI, PS, US/ZVI, US/PS, ZVI/PS, and US-ZVI/PS systems, respectively. Experimental results indicated that the highest removal efficiency of SDZ was ahieved in US-ZVI/PS system (97.4%), which were 2-44 times higher than that in other systems. Furthermore, the degradation efficiency of five typical SAs was achieved over 95%, demonstrating the effectiveness of the US ZVI/PS system for SAs removal. Also, quantum chemical computations for potential reactive sites of SAs and intermediate product detection by HPLCâMS/MS were performed. The radical attack on active sites of SAs, such as N atom (number 7), was the main reason for SAs removal in US-ZVI/PS system. Besides, the common degradation pathways of six typical SAs were defined as S-N bond cleavage, C-N bond cleavage, benzene ring hydroxylation, aniline oxidation, and R substituent oxidation. Interestingly, the unique pathway of "SO2 group extraction" was observed in the degradation of six-membered ring SAs. Therefore, the US-ZVI/PS system is a promising and cost-effective method for the removal of SAs and other refractory pollutants.
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Antibacterianos , Espectrometría de Masas en Tándem , Humanos , Sulfanilamida , Sulfadiazina , Sulfonamidas , HierroRESUMEN
BACKGROUND: Even though the serum anion gap (AG) is frequently measured in clinical practice, there is not much research that has examined long-term mortality in unselected adult patients. Our study's objective was to investigate how serum anion gap levels could be used to predict death in unselected participants. METHODS: The relationship between baseline serum AG levels and short-, intermediate-, and long-term all-cause mortality in unselected adult patients is examined using the Cox proportional risk analysis, smoothed curve fitting, subgroup analysis, and Kaplan-Meier survival curves. RESULTS: After screening the database using the appropriate method, a total of 26,270 patients were enrolled in our study for the final data analysis. Our study used smoothed curve fit plots and COX proportional risk regression models incorporating cubic spline functions to evaluate the association between AG levels and all-cause mortality in a non-selected population, and the results indicated a non-linear relationship. In the fully adjusted model, we found that AG levels were positively associated with 30-day, 90-day, 365-day, and 4-year all-cause mortality in unselected adult patients with HRs of 1.08 95% CIs (1.06, 1.09); 1.08 95% CIs (1.06, 1.09); 1.08 95% CIs (1.07, 1.08); 1.07 95% CIs (1.06, 1.07). CONCLUSION: Serum anion gap levels were positively correlated with all-cause mortality in unselected adult patients, with increasing levels of serum anion gap increasing patient mortality.
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Equilibrio Ácido-Base , Suero , Humanos , Adulto , Estudios Retrospectivos , Medición de RiesgoRESUMEN
To achieve cancer screening in any appointed position in 3D regions of the gastrointestinal (GI) tract such as esophagus, stomach and colon, a highly integrated dual hemisphere capsule robot (DHCR) with a novel three-layer nested structure is proposed. Based on tracking effect, in which the robotic axis is likely to be approximately coincident with the orientation of the space universal rotating magnetic field (SURMF) using the gyroscope dynamic balance, the dual hemisphere structure realizes the observation at a fixed-point in the passive mode and the rolling locomotion in the active mode by the dynamic posture control of the SURMF manipulation. The image acquisition module, wireless transmission module and driving actuator are tuned in a spherical structure, making the DHCR more compact and less invasive. To verify the maneuverability of the innovative DHCR both for observation at a fixed-point and navigation in curved intestine by aid of image, experiments are conducted in the simulated GI tract environment. The results show that the DHCR achieves effective conversion between posture adjustment and rolling locomotion, which lays a foundation for all-over inspection and medical operation inside 3D regions of the GI tract of human body.
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Endoscopía Capsular , Robótica , Diseño de Equipo , Tracto Gastrointestinal , Humanos , Intestinos , Campos MagnéticosRESUMEN
Soil salinity severely threatens plant growth and crop performance. Hydrogen sulfide (H2S), a plant signal molecule, has been implicated in the regulation of plant responses to salinity stress. However, it is unclear how the transcriptional network regulates H2S biosynthesis during salt stress response. In this study, we identify a rice NAC (NAM, ATAF and CUC) transcription factor, OsNAC35-like (OsNACL35), from a salt-tolerant cultivar 'Sea Rice 86' (SR86) and further show that it may have improved salt tolerance via enhanced H2S production. The expression of OsNACL35 was significantly upregulated by high salinity and hydrogen peroxide (H2O2). The OsNACL35 protein was localized predominantly in the nucleus and was found to have transactivation activity in yeast. The overexpression of OsNACL35 (OsNACL35-OE) in japonica cultivar Nipponbare ramatically increased resistance to salinity stress, whereas its dominant-negative constructs (SUPERMAN repression domain, SRDX) conferred hypersensitivity to salt stress in the transgenic lines at the vegetative stage. Moreover, the quantitative real-time PCR analysis showed that many stress-associated genes were differentially expressed in the OsNACL35-OE and OsNACL35-SRDX lines. Interestingly, the ectopic expression of OsNACL35 triggered a sharp increase in H2S content by upregulating the expression of a H2S biosynthetic gene, OsDCD1, upon salinity stress. Furthermore, the dual luciferase and yeast one-hybrid assays indicated that OsNACL35 directly upregulated the expression of OsDCD1 by binding to the promoter sequence of OsDCD1. Taken together, our observations illustrate that OsNACL35 acts as a positive regulator that links H2S production to salt stress tolerance, which may hold promising utility in breeding salt-tolerant rice cultivar.
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Sulfuro de Hidrógeno , Oryza , Regulación de la Expresión Génica de las Plantas , Hidrógeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/metabolismo , Oryza/metabolismo , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Saccharomyces cerevisiae/metabolismo , Tolerancia a la Sal/genética , Plantones/genética , Plantones/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/metabolismoRESUMEN
Rhodospirillum (Rsp.) rubrum is one of the most widely used model organisms in bacterial photosynthesis. This purple phototroph is characterized by the presence of both rhodoquinone (RQ) and ubiquinone as electron carriers and bacteriochlorophyll (BChl) a esterified at the propionic acid side chain by geranylgeraniol (BChl aG) instead of phytol. Despite intensive efforts, the structure of the light-harvesting-reaction center (LH1-RC) core complex from Rsp. rubrum remains at low resolutions. Using cryo-EM, here we present a robust new view of the Rsp. rubrum LH1-RC at 2.76 Å resolution. The LH1 complex forms a closed, slightly elliptical ring structure with 16 αß-polypeptides surrounding the RC. Our biochemical analysis detected RQ molecules in the purified LH1-RC, and the cryo-EM density map specifically positions RQ at the QA site in the RC. The geranylgeraniol side chains of BChl aG coordinated by LH1 ß-polypeptides exhibit a highly homologous tail-up conformation that allows for interactions with the bacteriochlorin rings of nearby LH1 α-associated BChls aG. The structure also revealed key protein-protein interactions in both N- and C-terminal regions of the LH1 αß-polypeptides, mainly within a face-to-face structural subunit. Our high-resolution Rsp. rubrum LH1-RC structure provides new insight for evaluating past experimental and computational results obtained with this old organism over many decades and lays the foundation for more detailed exploration of light-energy conversion, quinone transport, and structure-function relationships in this pigment-protein complex.
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BACKGROUND: Evidence regarding the relationship between the type of anaesthesia and length of hospital stay is controversial. Therefore, the objective of this research was to investigate whether the type of anaesthesia was independently related to the length of hospital stay in patients undergoing unilateral total knee arthroplasty (TKA) after adjusting for other covariates. METHODS: The present study was a cohort study. A total of 2622 participants underwent total knee arthroplasty (TKA) at a hospital in Singapore from 2013 to 1-1 to 2014-6-30. The target independent variable and the dependent variable were two types of anaesthesia and length of hospital stay, respectively. The covariates included age, BMI, hemoglobin (Hb), length of stay (LOS), duration of surgery, sex, ethnicity, American Society of Anesthesiologist (ASA) Status, smoking, obstructive sleep apnea (OSA), diabetes mellitus (DM), DM on insulin, ischemic heart disease (IHD), congestive cardiac failure (CCF), cerebrovascular accident (CVA), creatinine > 2 mg/dl, day of week of operation. Multivariate linear and logistic regression analyses were performed on the variables that might influence the choice of the two types of anaesthesia and the LOS. This association was then tested by subgroup analysis using hierarchical variables. RESULTS: The average age of 2366 selected participants was 66.57 ± 8.23 years old, and approximately 24.18% of them were male. The average LOS of all enrolled patients was 5.37 ± 4.87 days, 5.92 ± 6.20 days for patients receiving general anaesthesia (GA) and 5.09 ± 3.98 days for patients receiving regional anaesthesia (RA), P < 0.05. The results of fully adjusted linear regression showed that GA lasted 0.93 days longer than RA (ß = 0.93, 95% CI (0.54, 1.32)), P < 0.05. The results of fully adjusted logistic regression showed that LOS > 6 days was 45% higher for GA than for RA (OR = 1.45, 95% CI (1.15, 1.84)), P < 0.05. Through the subgroup analysis, the results were basically stable and reliable. CONCLUSION: Our study showed that GA increased the length of stay during unilateral TKA compared with RA. This finding needs to be validated in future studies.
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Anestesia de Conducción/métodos , Anestesia de Conducción/estadística & datos numéricos , Anestesia General/métodos , Anestesia General/estadística & datos numéricos , Artroplastia de Reemplazo de Rodilla/métodos , Tiempo de Internación/estadística & datos numéricos , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SingapurRESUMEN
We report a novel solid-state molecular device structure based on double self-assembled monolayers (D-SAM) incorporated into the suspended nanowire architecture to form a "Au|SAM-1||SAM-2|Au" junction. Using commercially available thiol molecules that are devoid of synthetic difficulty, we constructed a "Au|S-(CH2)6-ferrocene||SAM-2|Au" junction with various lengths and chemical structures of SAM-2 to tune the coupling between the ferrocene conductive molecular orbital and electrode of the junction. Combining low noise and a wide temperature range measurement, we demonstrated systematically modulated conduction depending on the length and chemical nature of SAM-2. Meanwhile, the transport mechanism transition from tunneling to hopping and the intermediate state accompanied by the current fluctuation due to the coexistence of the hopping and tunneling transport channels were observed. Considering the versatility of this solid-state D-SAM in modulating the electrode-molecule interface and electroactive groups, this strategy thus provides a novel facile strategy for tailorable nanoscale charge transport studies and functional molecular devices.
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The rapid development of microbiota research has remolded our view of human physiological and pathological processes. Among all the gastrointestinal microorganisms, Helicobacter pylori (H pylori) is probably the most notorious constituent. Although half of the adults worldwide are infected with H pylori, their clinical manifestations vary widely, suggesting other microorganisms beyond H pylori may play a role in determining clinical outcomes. Recently, many studies have put effort into elucidating the crosstalk within the human microbiota, some of which specifically explored the interplay between H pylori and other gastrointestinal microbial members. In this work, we reviewed these potential interactions. Meanwhile, the impacts of H pylori eradication therapy on gastrointestinal microbial homeostasis were summarized in terms of diversity, composition, functional capacity, and antibiotic resistance.
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Microbioma Gastrointestinal , Infecciones por Helicobacter , Adulto , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori , HumanosRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC) ranks as the fifth most frequent cancer worldwide, and the recurrence and migration of OSCC still pose large threats to patients. Long non-coding RNAs (lncRNAs) have recently emerged as crucial players in cancer development, and it is of great significance to understand the regulatory nexus of lncRNAs in OSCC. METHODS: Here, we identified a novel lncRNA, RP11-874J12.4, which is ectopically expressed in OSCC and facilitates OSCC. RESULTS: RP11-874J12.4 directly binds to and regulates miR-19a-5p. Interestingly, RP11-874J12.4 and miR-19a-5p form a negative regulatory loop that inhibits the expression of miR-19a-5p in OSCC. The expression of an oncogenic transcription factor, EBF1, is unleashed in OSCC due to the low expression of miR-19a-5p, which promotes the growth and migration of OSCC. CONCLUSION: Our data illustrate a regulatory axis of RP11-874J12.4/miR-19a-5P/EBF1 and an inhibitory loop with RP11-874J12.4 and miR-19a-5p. These data provide insights into the tumorigenesis of OSCC and the novel drug targets for OSCC.
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Carcinoma de Células Escamosas , MicroARNs/genética , Neoplasias de la Boca , ARN Largo no Codificante/genética , Carcinogénesis/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias de la Boca/genética , TransactivadoresRESUMEN
miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.