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Hippophae tibetana, belonging to the Elaeagnaceae family, is an endemic plant species of the Qinghai-Tibet Plateau, valued for its remarkable ecological restoration capabilities, as well as medicinal and edible properties. Despite being acknowledged as a useful species, its mitochondrial genome data and those of other species of the Elaeagnaceae family are lacking to date. In this study, we, for the first time, successfully assembled the mitochondrial genome of H. tibetana, which is 464,208 bp long and comprises 31 tRNA genes, 3 rRNA genes, 37 protein-coding genes, and 3 pseudogenes. Analysis of the genome revealed a high copy number of the trnM-CAT gene and a high prevalence of repetitive sequences, both of which likely contribute to genome rearrangement and adaptive evolution. Through nucleotide diversity and codon usage bias analyses, we identified specific genes that are crucial for adaptation to high-altitude conditions. Notably, genes such as atp6, ccmB, nad4L, and nad7 exhibited signs of positive selection, indicating the presence of unique adaptive traits for survival in extreme environments. Phylogenetic analysis confirmed the close relationship between the Elaeagnaceae family and other related families, whereas intergenomic sequence transfer analysis revealed a substantial presence of homologous fragments among the mitochondrial, chloroplast, and whole genomes, which may be linked to the high-altitude adaptation mechanisms of H. tibetana. The findings of this study not only enrich our knowledge of H. tibetana molecular biology but also advance our understanding of the adaptive evolution of plants on the Qinghai-Tibet Plateau. This study provides a solid scientific foundation for the molecular breeding, conservation, and utilization of H. tibetana genetic resources.
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Immunosenescence, the aging of the immune system, leads to functional deficiencies, particularly in T cells, which undergo significant changes. While numerous studies have investigated age-related T-cell phenotypes in healthy aging, senescent T cells have also been observed in younger populations during pathological conditions like cancer. This review summarizes the recent advancements in age-associated alterations and markers of T cells, mechanisms, and the relationship between senescent T cells and the tumor microenvironment. We also discuss potential strategies for targeting senescent T cells to prevent age-related diseases and enhance tumor immunotherapy efficacy.
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Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.
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Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain. Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations. Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality. Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (ß=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (ß=-0.127), showed an indirect effect on infertility mediated by SUA (ß=-0.0187; 95% CI, -0.041 to -0.003; P=0.046). Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.
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Estradiol , Infertilidad Femenina , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Globulina de Unión a Hormona Sexual , Testosterona , Ácido Úrico , Humanos , Femenino , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/genética , Ácido Úrico/sangre , Estradiol/sangre , Infertilidad Femenina/sangre , Infertilidad Femenina/genética , Testosterona/sangre , Población Blanca/genética , Estudio de Asociación del Genoma Completo , Europa (Continente)/epidemiología , Adulto , Estudios de Casos y ControlesRESUMEN
Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1- T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1- T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.
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Receptor 1 de Quimiocinas CX3C , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Linfocitos Infiltrantes de Tumor , Receptor de Muerte Celular Programada 1 , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Receptor 1 de Quimiocinas CX3C/metabolismo , Humanos , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Femenino , Apoptosis/efectos de los fármacos , Masculino , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/metabolismo , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismoRESUMEN
Due to continuous plantation of poplar, its growth and biomass accumulation may be negatively affected by the accumulation of allelochemicals such as para-hydroxybenzoic acid (pHBA) in soil. As photosynthesis is the most fundamental process in plants, it can be negatively impacted by pHBA stress. Therefore, it is crucial to improve photosynthetic capacity under pHBA stress to facilitate poplar plant growth. The mitogen-activated protein kinase (MAPK) cascade pathway is widely involved in environmental stress responses in plants. However, the regulation mechanisms of photosynthesis-related pathways by MAPK pathway genes under pHBA stress are still unclear. In this study, through transcriptome analysis and weighted gene co-expression network analysis, we observed that PeMPK7 overexpression in poplar can regulate the expression of photosynthesis-related genes and transcription factor genes, namely, WRKY1, WRKY33, and ERF3, during the early stage of pHBA stress. In addition, PeMPK7 can improve photosynthesis in poplar under long-term pHBA stress. Moreover, yeast two-hybrid and pull-down assays confirmed the interaction between PeMPK7 and PeMKK7/10. Based on these results, a schematic diagram of the pathways involved in the regulation of photosynthesis by PeMPK7 was constructed. This study provided novel insights into the molecular mechanisms of regulation of pHBA stress via MAPK cascade pathway.
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Regulación de la Expresión Génica de las Plantas , Parabenos , Fotosíntesis , Populus , Populus/genética , Populus/efectos de los fármacos , Populus/fisiología , Fotosíntesis/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Estrés Fisiológico , Hidroxibenzoatos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Contaminantes del Suelo/toxicidadRESUMEN
A nitrogen-doped carbon shell loaded with a gold and silver alloy (Au/Ag@NCS) was constructed for highly sensitive electrochemical detection of NO. The Au/Ag@NCS material was prepared by use of SiO2 particles as a template to polymerize imidazolium-based ionic liquids loaded with gold and silver salts, and subsequent carbonization treatment and template removal. The hollow structure of the carbon material acted as a carrier for electrochemical sensing, offering high specific surface area, large pore capacity, robust electron conductivity, and excellent mechanical stability. The inclusion of gold in the composite enhanced its catalytic and sensing capabilities, while silver oxidation was employed as a reference signal for accurate detection. By utilization of the Au/Ag@NCS-modified electrode, a wide detection range from 0.5 nM to 1.05 µM with a low detection limit of 0.32 nM was achieved for NO detection. The electrochemical sensor also exhibited high selectivity and excellent stability. The fabricated sensor was further utilized to explore the release of NO from breast cancer cells, revealing that the electrochemical platform could be regarded as an important method to study the daily tests of NO in clinical application.
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As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD4T mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD4T mice, accompanied by α-secretase activation and Aß reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.
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Enfermedad de Alzheimer , Humanos , Masculino , Ratones , Femenino , Animales , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ratones Transgénicos , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismo , Péptidos beta-Amiloides/metabolismo , Modelos Animales de EnfermedadRESUMEN
Photodynamic therapy (PDT) depends on the light-irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue-penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co-delivery of CRISPR-Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single-stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G-quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G-quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Ratones , Animales , Sistemas CRISPR-Cas , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes , Hemina , Peróxido de Hidrógeno , ARN Guía de Sistemas CRISPR-Cas , Nanopartículas/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Hipoxia , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
Streptococcus pyogenes (GAS) is one of the most virulent and infectious bacteria, severely threatening health and lives of people worldwide. Honey has been proven to have effective capability against GAS, but the underlying metabolites and mechanisms are still unclear. In this study, the Castanopsis honey (CH) showed significant antibacterial ability compared to other seven kinds of honey and artificial honey. Furthermore, the antibacterial metabolites and their targets in CH were screened by combined method of metabolomics, network pharmacology, and molecular docking. The results suggested that the activities of two antioxidant enzymes, glutathione peroxidase and tyrosyl tRNA synthetase identified as the primary targets, were significantly inhibited by CH, which significantly increased the level of oxidative stress in GAS. The results revealed a possibly novel mechanism regulating the oxidative stress and inhibits the growth in bacteria, providing strong experimental evidence to support the further development of CH as a novel antibacterial agent.
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Miel , Streptococcus pyogenes , Humanos , Farmacología en Red , Simulación del Acoplamiento Molecular , Antibacterianos/farmacología , MetabolómicaRESUMEN
Background: Few studies have evaluated the treatment of immunoglobulin A nephropathy (IgAN) patients with nephrotic syndrome (NS) and mesangioproliferative glomerulonephritis (MPGN). The aim of this study was to compare the therapeutic effects of oral glucocorticoids (GCS) combined with intravenous cyclophosphamide (CTX) and oral GCS alone in the treatment of the MPGN-IgAN patients with NS. Methods: Biopsy-proven primary IgAN patients who were aged ≥14 years at diagnosis, had coexistent NS and MPGN and estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2, and were treated by oral GCS combined with intravenous CTX or oral GCS alone for 6-12 months were retrospectively included. The patients in the GCS + CTX (prednisone 0.6-0.8 mg/kg/day and intravenous CTX 0.6-1.0 g monthly) or GCS (prednisone 0.8-1 mg/kg/day) group were rather matched at a 1:1 ratio on key characteristics by propensity score matching. The primary outcome was defined as either complete remission or partial remission at Month 24. The secondary outcome was a composite renal endpoint defined as a 50% decline in eGFR, doubling of serum creatinine or progression to end-stage kidney disease. Results: Among the 146 IgAN patients who met the inclusion criteria, 42 patients were enrolled in the GCS + CTX group, and 42 patients were enrolled in the GCS group after propensity score matching. The clinical and histological parameters were similar between the two groups. Remission occurred more frequently in the GCS + CTX group at Month 6 (88.1% vs 52.4%, P < 0.001), Month 12 (88.1% vs 56.1%, P = 0.001) and Month 24 (85.0% vs 47.5%, P < 0.001) than in the GCS group. Moreover, subgroup analysis revealed that the higher response rate at Month 24 in the GCS + CTX group than in the GCS group was also present in different subgroups defined by sex, age, eGFR or Oxford MEST-C. Notably, we found that eGFR decreased at a lower rate in patients from the GCS + CTX group than in patients from the GCS group [eGFR slope: 0.05(-3.09, 3.67) vs -2.56 (-11.30, 0.86) mL/min/1.73 m2/year, P = 0.03]. Based on multivariate Cox regression analysis, GCS + CTX treatment was found to be independently associated with a decrease in risk for the composite endpoint after adjusted by the International Risk Prediction Score with race (hazard ratio = 0.17, 95% confidence interval 0.04-0.83, P = .03). There was no significant difference in adverse events (50.0% vs 42.9%, P = 0.51) or serious adverse events (7.1% vs 11.9%, P = .71) between the two groups. Conclusions: Oral GCS combined with intravenous CTX is superior to GCS alone in treating MPGN-IgAN patients combined with NS. As the retrospective design and small sample size, our findings need to be validated by a prospective study.
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This study aimed to identify group variations in adolescent impulsivity and explore the connections between latent categories of impulsivity and psychological symptoms, social anxiety, and internet addiction. The research involved 2,378 participants from three middle schools in Guangdong Province, China. We assessed the impact of impulsivity levels (measured by BBIS) on depression (measured by KADS-11), anxiety (measured by SCARED), social anxiety (measured by SASC), and internet addiction (measured by YDQ). Latent profile analysis was employed to examine the diversity in adolescent impulsivity, establish latent classifications, and investigate the variances in psychological symptoms, social anxiety, and internet addiction. The middle school students were categorized into five latent groups based on their BBIS scores. Statistical analysis revealed five impulsivity categories, strongly linked to psychological symptoms and social anxiety but less strongly associated with internet addiction. The high impulsivity group (C5) exhibited higher scores in psychological symptoms and social anxiety compared to other groups, whereas the poor self-regulation group (C3) displayed greater psychological symptoms, social anxiety scores, and internet addiction than the impulsive behavior group (C4). Future investigations should investigate the underlying factors contributing to the observed differences among these groups.
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In this paper, we present the first attempt at determining where the achievable rate-distortion (R-D) performance bound in versatile video coding (VVC) intra coding is when considering the mutual dependency in the rate-distortion optimization (RDO) process. In particular, the abundant search space of encoding parameters in VVC intra coding is practically explored with a beam search-based joint rate-distortion optimization (BSJRDO) scheme. As such, the partitioning, prediction and transform decisions are jointly optimized across different coding units (CUs) with a customized search subset instead of the full space. To make the beam search process implementation-friendly for VVC, the dependencies among the CUs are truncated at different depths. To facilitate finer computational scalability, the beam size is flexibly adjusted based on the characteristics of the CUs, such that the operational points that satisfy different complexity demands for diverse applications can be practically obtained. The proposed BSJRDO approach, which fully conforms to the VVC decoding syntax, can serve as both the way toward the optimal RDO bound and a practical performance-boosting solution. BSJRDO is further implemented on a VVC coding platform (VVC Test model (VTM) 12.0), and extensive experiments show that BSJRDO can achieve 1.30% and 3.22% bit rate savings compared to the VTM anchor under the common test condition and low-bit-rate coding scenarios, respectively. Moreover, the performance gain can also be flexibly customized with different computational overheads.
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Strengthening the analysis and risk assessment of the pig epidemic will help to better prevent and mitigate epidemic risks and promote the high-quality development of the pig industry. Based on a systematic understanding of live pig epidemics, a risk assessment index system was constructed, and the spatial and temporal variation characteristics of pig epidemics in China were explored by the entropy method. In recent years, the overall trend in pig epidemics over time first increased and then decreased; in space, the acceleration of the spread of epidemics across the country weakened. China still faces challenges, including many types and a wide range of diseases, large total livestock breeding and weak epidemic prevention and control capacity, and a large risk of introduced foreign animal epidemics. The spatial and temporal variations in the pig epidemic risk were obvious; one high-risk area, two medium-high-risk areas and 10 medium-risk areas have been found in recent years, during which time, the epidemic risk was highest in Beijing, Hainan, Liaoning, Tibet and Zhejiang. However, there were significant differences in the regional distribution of the risk level of pig epidemics in different years. To further build a secure "defense system" for the high-quality development of the pig industry, it is recommended to improve the monitoring and early warning system of pig epidemic risk, perfect the pig epidemic prevention and control system, and strengthen the regional collaboration mechanism of epidemic prevention and control.
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Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are becoming powerful tools for disease biomarkers detection. Due to the specific recognition, cis-cleavage and nonspecific trans-cleavage capabilities, CRISPR/Cas systems have implemented the detection of nucleic acid targets (DNA and RNA) as well as non-nucleic acid targets (e.g., proteins, exosomes, cells, and small molecules). In this review, we first summarize the principles and characteristics of various CRISPR/Cas systems, including CRISPR/Cas9, Cas12, Cas13 and Cas14 systems. Then, various types of applications of CRISPR/Cas systems used in detecting nucleic and non-nucleic acid targets are introduced emphatically. Finally, the prospects and challenges of their applications in biosensing are discussed.
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Mitogen-activated protein kinase (MAPK) plays a crucial role in plant stress response. Poplar is one of the most important afforestation and timber species and inevitably encounters allelopathy effects during continuous cropping. para-hydroxybenzoic acid (pHBA) is a primary soil allelochemical, which can restrict the growth and biomass of poplar. However, the involvement of MAPKs in the underlying physiological and molecular regulatory mechanisms in response to pHBA stress remains unclear. In this study, PeMPK17, a gene encoding a group D MAPK, was cloned from Populus × euramericana. PeMPK17 protein was localized in both nucleus and plasma membrane. Quantitative real-time polymerase chain reaction analysis demonstrated that PeMPK17 expression in poplar increased when treated with pHBA, PEG, and H2O2. Exogenous pHBA and H2O2 induced PeMPK17 expression mediated by reactive oxygen species (ROS). The transgenic poplar plants overexpressing PeMPK17 demonstrated attenuated phenotypic injury, higher relative water content in leaves, and lower ion leakage under pHBA stress. In transgenic poplar, the activity and expression of antioxidant enzymes including superoxide dismutase, peroxidase, and catalase increased, while the content of H2O2, O2·-, and malondialdehyde decreased. These results suggested that PeMPK17 protects cell membranes from oxidative damage by removing excess ROS. In addition, overexpression of PeMPK17 promoted osmoprotectant accumulation including soluble sugar and free proline, which may aid in the regulation of ROS balance under pHBA treatment. Furthermore, the interaction between PeMPK17 and PeMKK7 was confirmed. Collectively, these data identify the molecular mechanisms and signal pathways associated with PeMPK17 that regulate pHBA response in poplar.
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The trans-cleavage property of CRISPR-Cas12a system makes it an excellent tool for disease diagnosis. Nevertheless, most methods based on CRISPR-Cas system still require pre-amplification of the target to achieve the desired detection sensitivity. Here we generate Framework-Hotspot reporters (FHRs) with different local densities to investigate their effect on trans-cleavage activity of Cas12a. We find that the cleavage efficiency increases and the cleavage rate accelerates with increasing reporter density. We further construct a modular sensing platform with CRISPR-Cas12a-based target recognition and FHR-based signal transduction. Encouragingly, this modular platform enables sensitive (100â fM) and rapid (<15â min) detection of pathogen nucleic acids without pre-amplification, as well as detection of tumor protein markers in clinical samples. The design provides a facile strategy for enhanced trans cleavage of Cas12a, which accelerates and broadens its applications in biosensing.
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Técnicas Biosensibles , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Biomarcadores de Tumor , Transducción de SeñalRESUMEN
In this study, naked oat bran albumin hydrolysates (NOBAH) were subjected to gel chromatography with Sephadex G-15, reverse phase-high liquid performance separation, and UPLC-ESI-MS/MS identification. Six safe peptides including Gly-Thr-Thr-Gly-Gly-Met-Gly-Thr (GTTGGMGT), Gln-Tyr-Val-Pro-Phe (QYVPF), Gly-Ala-Ala-Ala-Ala-Leu-Val (GAAAALV), Gly-Tyr-His-Gly-His (GYHGH), Gly-Leu-Arg-Ala-Ala-Ala-Ala-Ala-Ala-Glu-Gly-Gly (GLRAAAAAAEGG), and Pro-Ser-Ser-Pro-Pro-Ser (PSSPPS) were identified. Next, in silico screening demonstrated that QYVPF and GYHGH had both angiotensin-I-converting enzyme (ACE) inhibition activity (IC50: 243.36 and 321.94 µmol/L, respectively) and Zinc-chelating ability (14.85 and 0.32 mg/g, respectively). The inhibition kinetics demonstrated that QYVPF and GYHGH were both uncompetitive inhibitors of ACE. Molecular docking showed that QYVPF and GYHGH could bind, respectively, three and five active residues of ACE with short hydrogen bonds (but not belonging to any central pocket). QYVPF and GYHGH could bind, respectively, twenty-two and eleven residues through hydrophobic interactions. Moreover, GYHGH was able to affect zinc tetrahedral coordination in ACE by interacting with His383. The inhibition activities of QYVPF and GYHGH toward ACE were relatively resistant to gastrointestinal digestion. GYHGH improved zinc solubility in the intestines (p > 0.05) because its amino and carboxyl groups were chelating sites for zinc ions. These results suggest the potential applications of naked oat peptides for potential antihypertension or zinc fortification.