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Cancer chemotherapy is advancing as we understand how cellular mechanisms and drugs interact, particularly involving the enzyme MGMT, which repairs DNA damage that can cause cancer. This review examines MGMT's role in DNA repair, its impact on chemotherapy, and its complex interaction with radiation therapy. MGMT activity can both protect against mutations and cause drug resistance. Modulating MGMT could improve treatment efficacy and tailoring therapy to MGMT status may enhance patient outcomes. Understanding MGMT is crucial for developing precise cancer treatments and advancing patient care.
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To explore the impact of shade treatment on grape berries, 'Marselan' grape berries were bagged under different light transmission rates (100% (CK), 75% (A), 50% (B), 25% (C), 0% (D)). It was observed that this treatment delayed the ripening of the grape berries. The individual weight of the grape berries, as well as the content of fructose, glucose, soluble sugars, and organic acids in the berries, was measured at 90, 100, and 125 days after flowering (DAF90, DAF100, DAF125). The results revealed that shading treatment reduced the sugar content in grape berries; the levels of fructose and glucose were higher in the CK treatment compared to the other treatments, and they increased with the duration of the shading treatment. Conversely, the sucrose content exhibited the opposite trend. Additionally, as the weight of the grape berries increased, the content of soluble solids and soluble sugars in the berries also increased, while the titratable acidity decreased. Furthermore, 16 differentially expressed genes (DEGs) were identified in the photosynthesis-antenna protein pathway from the transcriptome sequencing data. Correlation analysis revealed that the expression levels of genes VIT_08s0007g02190 (Lhcb4) and VIT_15s0024g00040 (Lhca3) were positively correlated with sugar content in the berries at DAF100, but negatively correlated at DAF125. qRT-PCR results confirmed the correlation analysis. This indicates that shading grape clusters inhibits the expression of genes in the photosynthesis-antenna protein pathway in the grape berries, leading to a decrease in sugar content. This finding contributes to a deeper understanding of the impact mechanisms of grape cluster shading on berry quality, providing important scientific grounds for improving grape berry quality.
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Frutas , Regulación de la Expresión Génica de las Plantas , Fotosíntesis , Proteínas de Plantas , Azúcares , Vitis , Vitis/genética , Vitis/metabolismo , Vitis/efectos de la radiación , Frutas/genética , Frutas/metabolismo , Frutas/efectos de la radiación , Fotosíntesis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Azúcares/metabolismo , LuzRESUMEN
Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.
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Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , NeuroimagenRESUMEN
Microtubules (MTs) are dynamic components of the cytoskeleton and play essential roles in morphogenesis and maintenance of tissue and cell integrity. Despite recent advances in understanding MT ultrastructure, organization, and growth control, how cells regulate MT organization at the cell cortex remains poorly understood. The EFA-6/EFA6 proteins are recently identified membrane-associated proteins that inhibit cortical MT dynamics. Here, combining visualization of endogenously tagged C. elegans EFA-6 with genetic screening, we uncovered tubulin-dependent regulation of EFA-6 patterning. In the mature epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR). We further show the EFA-6 IDR is sufficient to form biomolecular condensates in vitro. In screens for mutants with altered GFP::EFA-6 localization, we identified a novel gain-of-function (gf) mutation in an α-tubulin tba-1 that induces ectopic EFA-6 foci in multiple cell types. tba-1(gf) animals exhibit temperature-sensitive embryonic lethality, which is partially suppressed by efa-6(lf), indicating the interaction between tubulins and EFA-6 is important for normal development. TBA-1(gf) shows reduced incorporation into filamentous MTs but has otherwise mild effects on cellular MT organization. The ability of TBA-1(gf) to trigger ectopic EFA-6 foci formation requires ß-tubulin TBB-2 and the chaperon EVL-20/Arl2. The tba-1(gf)-induced EFA-6 foci display slower turnover, contain the MT-associated protein TAC-1/TACC, and require the EFA-6 MTED. Our results reveal a novel crosstalk between cellular tubulins and cortical MT regulators in vivo.
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We are documenting the case of An 11-year-old girl who has been followed up at our out-patient clinic since birth with clinical presentations including intrauterine growth restriction, recurrent periodic fever in infancy, hypotonia, global developmental delay, liver function impairment with cirrhotic changes, and clinodactyly. Congenital abnormalities were suspected but a series of examinations including brain MRI, liver biopsy and muscle biopsy yielded insignificant findings. Whole genome sequencing (WGS) was conducted and revealed three novel mutations (c2T > G, c1826T > C, c.556-560delAGTAAinsCT) of the COG5 gene. A diagnosis of COG5-congenital disorders of glycosylation (COG5-CDG, or CDG IIi), with neurologic presentation was established. Sanger sequencing in the patient and her parents confirmed the compound heterozygous mutation. Upon literature review, we identified the patient as the first case of COG5-CDG in Taiwan. Our study enhances the clarity of the correlation between the mutative genes and the presentation of COG5-CDG.
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BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.
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Resección Endoscópica de la Mucosa , Inhibidores de la Bomba de Protones , Pirroles , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Gástrica , Sulfonamidas , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Sulfonamidas/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Pirroles/uso terapéutico , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Resultado del TratamientoRESUMEN
Manipulating the structural and kinetic dissociation processes of water at the catalyst-electrolyte interface is vital for alkaline hydrogen evolution reactions (HER) at industrial current density. This is seldom actualized due to the intricacies of the electrochemical reaction interface. Herein, this work introduces a rapid, nonequilibrium cooling technique for synthesizing ternary Turing catalysts with short-range ordered structures (denoted as FeNiRu/C). These advanced structures empower the FeNiRu/C to exhibit excellent HER performance in 1 m KOH with an ultralow overpotential of 6.5 and 166.2 mV at 10 and 1000 mA cm-2, respectively, and a specific activity 7.3 times higher than that of Pt/C. Comprehensive mechanistic analyses reveal that abundant atomic species form asymmetric atomic electric fields on the catalyst surface inducing a directed evolution and the dissociation process of interfacial H2O molecules. In addition, the locally topologized structure effectively mitigates the high hydrogen coverage of the active site induced by the high current density. The establishment of the relationship between free water population and HER activity provides a new paradigm for the design of industrially relevant high performance alkaline HER catalysts.
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BACKGROUND: Adelphocoris suturalis is a destructive pest that attacks > 270 plants, including cotton, maize, soybean, and fruit trees. Adelphocoris suturalis can cause tremendous crop losses when the density exceeds economic thresholds, but because it can be both phytophagous and zoophytophagous it can serve as a natural enemy of other pests when the density is below the economic threshold. Effective control of its population is beneficial for maximizing yield and profits. RNA interference (RNAi) has potential to be a viable alternative to conventional pesticide-based pest management, but the lack of efficient double-stranded RNA (dsRNA) delivery systems and candidate genes are currently limiting factors for field applications. RESULTS: In this study, RNAi of juvenile hormone (JH) receptor components methoprene-tolerant (Met)/Taiman (Tai) in Adelphocoris suturalis reduced fertility. Based on this reproductive role, we targeted Adelphocoris suturalis Met and Tai for knockdown by coupling nanomaterial-dsRNA complexes with a transdermal spray delivery system. Within 12 h of adult emergence, females were sprayed with star polycation (SPc)-dsRNA formulations and the RNAi effects were assessed over time. RNAi knockdown efficiencies of 39-58% were observed at 5 days post-treatment and abnormal ovarian development was apparent by 10 days post-treatment. CONCLUSION: Our results show that spray-induced and nanocarrier-delivered gene silencing (SI-NDGS) system targeting JH signal genes effectively impaired oviposition, thus developing a novel RNA fertility inhibitor to control Adelphocoris suturalis populations. These results give new perspective on pest management and suggest broad prospects for field applications. © 2024 Society of Chemical Industry.
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Interferencia de ARN , Animales , Femenino , ARN Bicatenario/genética , ARN Bicatenario/farmacología , Fertilidad/efectos de los fármacos , Control de Insectos/métodos , Hormonas Juveniles/farmacología , Heterópteros/genética , Heterópteros/efectos de los fármacos , Heterópteros/crecimiento & desarrollo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Silenciador del GenRESUMEN
OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.
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Puntos de Acupuntura , Electroacupuntura , Ratas , Animales , Ratas Sprague-Dawley , Ratas Wistar , Dolor , Neuronas , Inflamación/terapia , Analgésicos/efectos adversos , Médula EspinalRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 was one of the most devastating public health issues in recent decades. The ophthalmology community is as concerned about the COVID-19 pandemic as the global public health community is, as COVID-19 was recognized to affect multiple organs in the human body, including the eyes, early in the course of the outbreak. Ophthalmic manifestations of COVID-19 are highly variable and could range from mild ocular surface abnormalities to potentially sight and life-threatening orbital and neuro-ophthalmic diseases. Furthermore, ophthalmic manifestations may also be the presenting or the only findings in COVID-19 infections. Meanwhile, global vaccination campaigns to attain herd immunity in different populations are the major strategy to mitigate the pandemic. As novel vaccinations against COVID-19 emerged, so were reports on adverse ophthalmic reactions potentially related to such. As the world enters a post-pandemic state where COVID-19 continues to exist and evolve as an endemic globally, the ophthalmology community ought to be aware of and keep abreast of the latest knowledge of ophthalmic associations with COVID-19 and its vaccinations. This review is a summary of the latest literature on the ophthalmic manifestations of COVID-19 and the adverse ophthalmic reactions related to its vaccinations.
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COVID-19 , Oftalmopatías , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias , SARS-CoV-2 , Oftalmopatías/epidemiología , Oftalmopatías/etiología , Vacunación/efectos adversosRESUMEN
Here, Molecular Cell talks to first and co-corresponding author Lizhen Chen and co-corresponding authors Shasha Chong and Zhijie "Jason" Liu about their paper, ''Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions'' (in this issue of Molecular Cell) and their scientific journeys until now.
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BACKGROUND: Adelphocoris suturalis (Hemiptera: Miridae) is a notorious agricultural pest, which causes serious economic losses to a diverse range of agricultural crops around the world. The poor understanding of its genomic characteristics has seriously hindered the establishment of sustainable and environment-friendly agricultural pest management through biotechnology and biological insecticides. RESULTS: Here, we report a chromosome-level assembled genome of A. suturalis by integrating Illumina short reads, PacBio, 10x Chromium, and Hi-C mapping technologies. The resulting 1.29 Gb assembly contains twelve chromosomal pseudomolecules with an N50 of 1.4 and 120.6 Mb for the contigs and scaffolds, respectively, and carries 20,010 protein-coding genes. The considerable size of the A. suturalis genome is predominantly attributed to a high amount of retrotransposons, especially long interspersed nuclear elements (LINEs). Transcriptomic and phylogenetic analyses suggest that A. suturalis-specific candidate effectors, and expansion and expression of gene families associated with omnivory, insecticide resistance and reproductive characteristics, such as digestion, detoxification, chemosensory receptors and long-distance migration likely contribute to its strong environmental adaptability and ability to damage crops. Additionally, 19 highly credible effector candidates were identified and transiently overexpressed in Nicotiana benthamiana for functional assays and potential targeting for insect resistance genetic engineering. CONCLUSIONS: The high-quality genome of A. suturalis provides an important genomic landscape for further investigations into the mechanisms of omnivory, insecticide resistance and survival adaptation, and for the development of integrated management strategies.
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Genómica , Resistencia a los Insecticidas , Resistencia a los Insecticidas/genética , Filogenia , Agricultura , Productos Agrícolas , CromosomasRESUMEN
Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates through multivalent interactions mediated by its N-terminal intrinsically disordered region (IDR) to orchestrate enhancer assembly in response to androgen signaling. AR IDR can be substituted by IDRs from selective proteins for AR condensation capacity and its function on enhancers. Expansion of the poly(Q) track within AR IDR results in a higher AR condensation propensity as measured by multiple methods, including live-cell single-molecule microscopy. Either weakening or strengthening AR condensation propensity impairs its heterotypic multivalent interactions with other enhancer components and diminishes its transcriptional activity. Our work reveals the requirement of an optimal level of AR condensation in mediating enhancer assembly and suggests that alteration of the fine-tuned multivalent IDR-IDR interactions might underlie AR-related human pathologies.
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Elementos de Facilitación Genéticos , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hormonas , Transducción de SeñalRESUMEN
Carbon dots (CDs), a new type of carbon-based fluorescent nanomaterial, have attracted widespread attention because of their numerous excellent properties. Lignocellulosic biomass is the most abundant renewable natural resource and possesses broad potential to manufacture different composite and smart materials. Numerous studies have explored the potential of using the components (such as cellulose, hemicellulose, and lignin) in lignocellulosic biomass to produce CDs. There are few papers systemically aiming in the review of the state-of-the-art works related to lignocellulosic biomass-derived CDs. In this review, the significant advances in synthesis processes, formation mechanisms, structural characteristics, optical properties, and applications of lignocellulosic biomass-based CDs such as cellulose-based CDs, hemicellulose-based CDs and lignin-based CDs in latest research are reviewed. In addition, future research directions on the improvement of the synthesis technology of CDs using lignocellulosic biomass as raw materials to enhance the properties of CDs are proposed. This review will serve as a road map for scientists engaged in research and exploring more applications of CDs in different science fields to achieve the highest material performance goals of CDs.
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During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.
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Pueblo Asiatico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , China , Data Warehousing , Bases de Datos Factuales , NeurocienciasRESUMEN
A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.
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Úlceras Bucales , Animales , Ratas , Úlceras Bucales/tratamiento farmacológico , Capsaicina , Gelatina , Películas Cinematográficas , Material ParticuladoRESUMEN
Improving the anaerobic treatment performance of waste activated sludge (WAS) to achieve resource recovery is an indispensable requirement to reduce carbon emissions, minimize and stabilize biosolids. In this study, a novel strategy by using urea hydrogen peroxide (UHP) to enhance SCFAs production through accelerating WAS disintegration, degrading recalcitrant substances and alleviating competitive suppression of methanogens. The SCFAs production and acetate proportion rose from 436.9 mg COD/L and 31.3% to 3102.6 mg COD/L and 54.1%, respectively, when UHP grew from 0 to 80 mg/g TSS. Mechanism investigation revealed that OH, O2 and urea were the major contributors to accelerate WAS disintegration with the sequence of OH> O2 > urea. Function microbes related to acidification and genes associated with acetate production ([EC:2.3.1.8] and [EC:2.7.2.1]) were upregulated while genes encoding propionic acid production ([EC:6.4.1.3] and [EC:6.2.1.1]) were downregulated. These results raised the application prospects of UHP in WAS resource utilization.
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Ácidos Grasos Volátiles , Aguas del Alcantarillado , Fermentación , Peróxido de Carbamida , Acetatos , Concentración de Iones de HidrógenoRESUMEN
The loss of proteostasis due to reduced efficiency of protein degradation pathways plays a key role in multiple age-related diseases and is a hallmark of the aging process. Paradoxically, we have previously reported that the Caenorhabditis elegans rpn-10(ok1865) mutant, which lacks the RPN-10/RPN10/PSMD4 subunit of the 19S regulatory particle of the 26S proteasome, exhibits enhanced cytosolic proteostasis, elevated stress resistance and extended lifespan, despite possessing reduced proteasome function. However, the response of this mutant against threats to endoplasmic reticulum (ER) homeostasis and proteostasis was unknown. Here, we find that the rpn-10 mutant is highly ER stress resistant compared to the wildtype. Under unstressed conditions, the ER unfolded protein response (UPR) is activated in the rpn-10 mutant as signified by increased xbp-1 splicing. This primed response appears to alter ER homeostasis through the upregulated expression of genes involved in ER protein quality control (ERQC), including those in the ER-associated protein degradation (ERAD) pathway. Pertinently, we find that ERQC is critical for the rpn-10 mutant longevity. These changes also alter ER proteostasis, as studied using the C. elegans alpha-1 antitrypsin (AAT) deficiency model, which comprises an intestinal ER-localised transgenic reporter of an aggregation-prone form of AAT called ATZ. The rpn-10 mutant shows a significant reduction in the accumulation of the ATZ reporter, thus indicating that its ER proteostasis is augmented. Via a genetic screen for suppressors of decreased ATZ aggregation in the rpn-10 mutant, we then identified ecps-2/H04D03.3, a novel ortholog of the proteasome-associated adaptor and scaffold protein ECM29/ECPAS. We further show that ecps-2 is required for improved ER proteostasis as well as lifespan extension of the rpn-10 mutant. Thus, we propose that ECPS-2-proteasome functional interactions, alongside additional putative molecular processes, contribute to a novel ERQC adaptation which underlies the superior proteostasis and longevity of the rpn-10 mutant.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retículo Endoplásmico/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Respuesta de Proteína Desplegada/genéticaRESUMEN
PURPOSE: Glioma patients have varying degrees of psychiatric symptoms, which severely affect the quality of life of patients and their families. The present study investigated the correlation between preoperative psychiatric symptoms and local cerebral perfusion parameters of in glioma patients. PATIENTS AND METHODS: The depression, anxiety, and cognitive impairment (CI) scores of 39 patients were assessed separately, and all of the patients underwent a preoperative perfusion computed tomography scan. RESULTS: This study found that: (1) The incidence of preoperative symptoms of depression, anxiety, and CI was 46.15%, 48.72%, and 25.64%, respectively. (2) Cerebral blood volume (CBV) (lesion-sided [LS] occipital lobe white matter [WM] and parietal lobe WM and normal-sided temporal lobe WM), permeability surface (PS) (LS temporal lobe gray matter [GM] and parietal lobe WM) in the depression group were significantly decreased (p < .05). (3) CBV (LS occipital lobe WM), cerebral blood flow (LS parietal lobe GM, centrum ovale and frontal lobe WM and normal-sided frontal lobe WM, temporal lobe WM and parietal lobe WM), and mean transition time (MTT) (normal-sided frontal lobe WM and temporal lobe WM) in the anxiety group were significantly increased (p < .05). (4) CBV (LS temporal lobe GM), MTT (LS anterior limb of internal capsule), and PS (LS thalamus) in the CI group were significantly increased (p < .05). CONCLUSION: This study showed that glioma patients had different levels of psychological distress in glioma patients before surgery, which may be related to the changes in brain perfusion caused by the tumor.
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Disfunción Cognitiva , Glioma , Humanos , Imagen por Resonancia Magnética/métodos , Depresión/diagnóstico por imagen , Depresión/etiología , Calidad de Vida , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Glioma/complicaciones , Glioma/diagnóstico por imagen , Glioma/cirugía , Ansiedad/diagnóstico por imagen , Ansiedad/etiología , Tomografía Computarizada por Rayos X , Circulación Cerebrovascular/fisiologíaRESUMEN
The development of electrochemical DNA biosensors has been limited by their reliability and reproducibility due to many interfering factors such as electrode properties, DNA surface densities, and complex biological samples. In this work, we developed a nanobalance polyA hairpin probe (polyA-HP), which was effectively assembled onto the gold electrode surface through the affinity between the central polyA fragment and the Au surface. One flanking probe of the polyA-HP captured the target sequence together with a MB-labeled signal probe, and the other flanking probe captured a reference probe simultaneously. The MB signal related to the amount of target was normalized by the reference Fc signal; thus, the signal-to-noise (S/N) was as high as 2000, and the reproducibility was remarkably improved to 2.77%, even facing deliberately changed experiment conditions. By designing a hairpin structure at the terminal of the polyA-HP, the selectivity and specificity were dramatically improved for the analysis of mismatched sequences. The analysis performance of biological samples was dramatically improved after normalization, which is critical for its practicability. Our novel biosensor is a universal single-molecule platform for ratiometric biosensors with excellent performance in real samples, indicating great potential for next-generation high-precision electrochemical sensors.