RESUMEN
Objective: Drug-induced liver injury (DILI), a type of acute inflammation, has sparked significant concern owing to its unpredictability and severity. Psoraleae Fructus (PF), an edible Chinese herb widely used in traditional Chinese medicine (TCM), causes liver injury. Therefore, the elucidation of the mechanism underlying PF-induced liver injury and the search for more effective means of detoxification using herbal compatibility has become an urgent issue. This study evaluated the hepatoprotective effects of Paeoniae Radix Alba (PRA), a hepatoprotective Chinese medicine, on PF-induced liver injury and explored the underlying mechanisms. Methods: A rat model of lipopolysaccharide (LPS)-induced immune stress was established to evaluate the hepatotoxicity of PF and the detoxifying effect of PRA. Subsequently, inflammatory pathways were identified using network pharmacology. Finally, the molecular mechanism by which PRA alleviates PF-induced liver injury was validated using an inflammasome activation model in bone marrow-derived macrophages (BMDMs). Results: In vivo, hepatocytes in rats treated with LPS + PF exhibited massive inflammatory infiltration and apoptosis, and the expression of liver injury indicators and inflammatory factors was significantly upregulated, which was reversed by PRA pretreatment. Network pharmacology showed that PRA alleviated PF-induced liver injury and was associated with the NOD-like receptor signaling pathway. Moreover, PF directly induced inflammasome activation in LPS-primed BMDMs which in turn induced caspase-1 activation and the secretion of downstream effector cytokines such as IL-1ß. PRA pretreatment inhibited PF-induced activation of the NLRP3 inflammasome by mitigating the accumulation of mitochondrial reactive oxygen species (mtROS). Conclusions: The present study demonstrates that PRA alleviated PF induced-liver injury by inhibiting NLRP3 inflammasome activation. The results of this study are expected to inform the prevention and control of PF-induced hepatotoxicity in clinical practice.
RESUMEN
Lilac (Syringa oblata) is a well-known horticultural plant, and its aromatic heartwood is widely utilized in Traditional Mongolian Medicine for treating angina. However, limited research on the dynamic changes and mechanisms of aromatic substance formation during heartwood development hinders the analysis and utilization of its medicinal components. In this study, volatile metabolome analysis revealed that sesquiterpenes are the primary metabolites responsible for the aroma in heartwood, with cadinane and eremophilane types being the most prevalent. Among the identified sesquiterpene synthases, SoSTPS1-5 exhibited significantly increased expression in heartwood formation and was selected for further investigation. Molecular docking simulations predicted multiple amino acid binding sites and confirmed its ability to catalyze the formation of eremophilane, copaene, cadinane, germacrane, and elemane-type sesquiterpenes from FPP (farnesyl pyrophosphate). Co-expression and promoter analysis suggested a transcriptional regulatory network primarily involving WRKY transcription factors. Additionally, aiotic and biotic stress inducers, such as Ag+, Fusarium oxysporum, and especially MeJA, were found to activate the expression of SoSTPS1-5 and promote sesquiterpene accumulation. This study provides insights into the basis of medicinal substance formation and the potential mechanisms of sesquiterpene accumulation in lilac heartwood, laying a foundation for future research on the biosynthesis and utilization of its medicinal components.
Asunto(s)
Proteínas de Plantas , Sesquiterpenos , Sesquiterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Simulación del Acoplamiento Molecular , Regulación de la Expresión Génica de las Plantas , Transferasas Alquil y Aril/metabolismo , Transferasas Alquil y Aril/genética , Madera/metabolismoRESUMEN
AIM OF THE STUDY: To study the cross-border regulation of immunity and energy metabolism by ginseng miRNA156, and to provide a new perspective for further exploring the possibility of ginseng miRNA156 as a pharmacodynamic substance. MATERIALS AND METHODS: Combined with the previous research results of our research group, miRNA156 with high expression in blood sequencing of intragastrically administered with ginseng decoction was selected. Bioinformatics analysis was performed on the selected differential miRNA156. The target genes of differential miRNA156 were mainly enriched in metabolic, immune and other signaling pathways. According to the analysis results, the experimental part will use qi deficiency fatigue model and RAW264.7 cells. The contents of lactic acid (LA), creatine kinase (CK), blood urea nitrogen (BUN), lactate dehydrogenase (LD), liver glycogen (LG), muscle glycogen (MG), interleukin 4 (IL-4), matrix metallo-proteinase 9 (MMP-9), superoxide dismutase (SOD), malondialdehyde, phosphor-enolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6pase), nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured after administration of miRNA156. RESULTS: Ginseng miRNA156 can accelerate the removal of metabolic waste during exercise. Increase the glycogen reserve in, provide energy for the body, regulate the activity of key gluconeogenesis enzyme phosphorus, improve the energy metabolism system of, and enhance the endurance of fatigue mice. The contents of matrix metalloproteinase 9, superoxide dismutase and malondialdehyde were affected, and the content of TNF-α in the supernatant of RAW264.7 cells was significantly increased, which had certain antioxidant capacity and potential immunomodulatory effects. CONCLUSION: Ginseng miRNA156 has a certain regulatory effect on the energy metabolism and immune function of mice, which makes it possible to regulate the cross-species regulation of ginseng miRNA in theory, provides ideas for ginseng miRNA to become a new pharmacodynamic substance.
Asunto(s)
Metabolismo Energético , MicroARNs , Panax , Animales , Panax/genética , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Metabolismo Energético/genética , Células RAW 264.7 , Masculino , Fatiga/genética , Hígado/metabolismo , Hígado/inmunología , Glucógeno/metabolismoRESUMEN
OBJECTIVE: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. METHODS: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. RESULTS: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. CONCLUSIONS: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.
Asunto(s)
Barrera Hematoencefálica , Dasatinib , Estrés Oxidativo , Quercetina , Animales , Masculino , Dasatinib/farmacología , Dasatinib/uso terapéutico , Quercetina/farmacología , Quercetina/uso terapéutico , Ratones , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Respuesta al Choque Térmico/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Quimioterapia Combinada , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Cognición/efectos de los fármacosRESUMEN
Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.
Asunto(s)
Transferencia de Gen Horizontal , Simbiosis , Avispas , Wolbachia , Animales , Wolbachia/fisiología , Wolbachia/genética , Avispas/fisiología , Avispas/microbiología , Avispas/genética , Simbiosis/genética , Femenino , Masculino , Partenogénesis/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Procesos de Determinación del Sexo/genéticaRESUMEN
BACKGROUND: Obesity affects approximately 800 million people worldwide and may contribute to various diseases, especially cardiovascular and cerebrovascular conditions. Fat distribution and content represent two related yet distinct axes determining the impact of adipose tissue on health. Unlike traditional fat measurement indices, which often overlook fat distribution, the Chinese visceral adiposity index (CVAI) is a novel metric used to assess visceral fat accumulation and associated health risks. Our objective is to evaluate its association with the risk of cardiovascular and cerebrovascular diseases. METHODS: A nationwide longitudinal study spanning 9 years was conducted to investigate both the effects of baseline CVAI levels (classified as low and high) and dynamic changes in CVAI over time, including maintenance of low CVAI, transition from low to high, transition from high to low, and maintenance of high CVAI. Continuous scales (restricted cubic spline curves) and categorical scales (Kaplan-Meier curves and multivariable Cox regression analyses) were utilized to evaluate the relationship between CVAI and cardiovascular and cerebrovascular diseases. Furthermore, subgroup analyses were conducted to investigate potential variations. RESULTS: Totally 1761 individuals (22.82%) experienced primary outcomes among 7717 participants. In the fully adjusted model, for each standard deviation increase in CVAI, there was a significant increase in the risk of primary outcomes [1.20 (95%CI: 1.14-1.27)], particularly pronounced in the high CVAI group [1.38 (95%CI: 1.25-1.54)] compared to low CVAI group. Regarding transition patterns, individuals who consistently maintained high CVAI demonstrated the highest risk ratio compared to those who consistently maintained low CVAI [1.51 (95%CI: 1.31-1.74)], followed by individuals transitioning from low to high CVAI [1.22 (95% CI: 1.01-1.47)]. Analysis of restricted cubic spline curves indicated a positive dose-response relationship between CVAI and risk of primary outcomes (p for non-linear = 0.596). Subgroup analyses results suggest that middle-aged individuals with high CVAI face a notably greater risk of cardiovascular and cerebrovascular diseases in contrast to elderly individuals [1.75 (95% CI: 1.53-1.99)]. CONCLUSION: This study validates a significant association between baseline levels of CVAI and its dynamic changes with the risk of cardiovascular and cerebrovascular diseases. Vigilant monitoring and effective management of CVAI significantly contribute to early prevention and risk stratification of cardiovascular and cerebrovascular diseases.
Asunto(s)
Adiposidad , Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Grasa Intraabdominal , Humanos , Masculino , Trastornos Cerebrovasculares/epidemiología , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Grasa Intraabdominal/fisiopatología , Estudios Longitudinales , Adulto , Anciano , Factores de Riesgo , China/epidemiología , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Estudios de Cohortes , Pueblos del Este de AsiaRESUMEN
The discovery of superconductivity in twisted bilayer graphene has reignited enthusiasm in the field of flat-band superconductivity. However, important challenges remain, such as constructing a flat-band structure and inducing a superconducting state in materials. Here, we successfully achieved superconductivity in Bi2O2Se by pressure-tuning the flat-band electronic structure. Experimental measurements combined with theoretical calculations reveal that the occurrence of pressure-induced superconductivity at 30 GPa is associated with a flat-band electronic structure near the Fermi level. Moreover, in Bi2O2Se, a van Hove singularity is observed at the Fermi level alongside pronounced Fermi surface nesting. These remarkable features play a crucial role in promoting strong electron-phonon interactions, thus potentially enhancing the superconducting properties of the material. These findings demonstrate that pressure offers a potential experimental strategy for precisely tuning the flat band and achieving superconductivity.
RESUMEN
We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a â¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.
Asunto(s)
Artemisia annua , Artemisininas , Grafito , MicroARNs , Fenómenos Fisiológicos , Plantas Medicinales , Artemisia annua/genética , Artemisia annua/metabolismo , Grafito/metabolismo , Grafito/farmacología , Peróxido de Hidrógeno/metabolismo , Plantas Medicinales/genética , Artemisininas/metabolismo , Artemisininas/farmacologíaRESUMEN
Genetic logic gates can be employed in metabolic engineering and synthetic biology to regulate gene expression based on diverse inputs. Design of tunable genetic logic gates with versatile dynamic performance is essential for expanding the usability of these toolsets. Here, using the p-coumaric acid biosensor system as a proof-of-concept, we initially investigated the parameters influencing the buffer (BUF) genetic logic gates. Subsequently, integrating binding sequences from the p-coumaric acid biosensor system and tetR or lacI regulation systems into a constitutive promoter yielded AND genetic logic gates. Additionally, characterized antisense RNAs (asRNAs) or single guide RNAs (sgRNAs) with various repression efficiencies were combined with BUF gates to construct a suite of p-coumaric acid-triggered NOT genetic logic gates. Finally, the designed BUF and NOT gates were combined to construct bifunctional genetic circuits that were subjected to orthogonality evaluation. The genetic logic gates established in this study can serve as valuable tools in future applications of metabolic engineering and synthetic biology.
Asunto(s)
Lógica , ARN Guía de Sistemas CRISPR-Cas , Regiones Promotoras Genéticas/genéticaRESUMEN
Transcriptional factors-based biosensors are commonly used in metabolic engineering for inducible control of gene expression and related applications such as high-throughput screening and dynamic pathway regulations. Mining for novel transcriptional factors is essential for expanding the usability of these toolsets. Here, we report the identification, characterization, and engineering of a phenolic acid responsive regulator PadR from Bacillus amyloliquefaciens (BaPadR). This BaPadR-based biosensor system showed a unique ligand preference and exhibited a high output strength comparable to that of commonly used inducible expression systems. Through engineering the DNA binding region of BaPadR, we further enhanced the dynamic range of the biosensor system. The DNA sequences that are responsible for BaPadR recognition were located by promoter truncation and hybrid promoter building. To further explore the tunability of the sensor system, base substitutions were performed on the BaPadR binding region of the phenolic acid decarboxylase promoter (PpadC) and the hybrid promoter. This novel biosensor system can serve as a valuable tool in future synthetic biology applications.
Asunto(s)
Bacillus amyloliquefaciens , Técnicas Biosensibles , Bacillus amyloliquefaciens/genética , Bacillus amyloliquefaciens/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hidroxibenzoatos/metabolismo , Regiones Promotoras Genéticas/genética , Ingeniería MetabólicaRESUMEN
Interlayer coupling and stacking order play essential roles in shaping the exotic electronic properties of two-dimensional materials. Here, we employ restacked TaS2âa novel transition metal dichalcogenide (TMD) with weak vdW bonding and twisted anglesâto investigate the strain effects of interlayer modulation on the electronic properties. Under pressure, an unexpected transition from metallic to semiconducting-like states occurs. Superconductivity coexists with the semiconducting-like state over a wide pressure range, which has never before been observed in TMDs. Upon further compression, a new superconducting SC-II state emerges without structural evolution and gradually replaces the initial SC-I state. The emerging SC-II state exhibits robust zero-resistance superconductivity and an ultrahigh upper critical field. The abundant electronic state changes in RS-TaS2 are strongly related to band-structure engineering resulting from pressure-induced interlayer stacking angle modulation. Our results reveal the remarkable effect of interlayer rearrangement on electronic properties and provide a special way to explore the unique properties of 2D materials.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Anethum graveolens L. (dill), which has been used as a medicine, spice and aromatic plant since ancient times, is not only a traditional Chinese medicines but also an important medicinal and functional food in Europe and Central and South Asia. In ethnomedicine, dill reportedly exerts a protective effect on the liver and has been widely used as a traditional medicine for the treatment of jaundice in the liver and spleen and inflammatory gout diseases in Saudi Arabia. Furthermore, studies have found that dill can regulate the NAT2 enzyme, and this plant was thus selected to study its alleviating effect on isoniazid liver injury. AIM OF THE STUDY: The purpose of this study was to explore the effect of dill on alleviating liver injury induced by hydrazine compounds represented by isoniazid through the use of network pharmacology combined with in vivo and in vitro experimental verifications. MATERIALS AND METHODS: First, we screened the key targets of dill in the treatment of liver injury through the use of network pharmacology; we then performed GO and KEGG pathway enrichment analyses using the DAVID database. We also verified the alleviative and anti-inflammatory effects of dill on isoniazid liver injury in rats by animal experiments. We further investigated the modulating effect of dill on the enzymatic activity of NAT2, a common metabolizing enzyme of hydrazine compounds. RESULTS: A total of 111 key targets were screened through network pharmacology. In vivo experiments showed that dill reduced the amount of inflammatory factors produced by isoniazid, such as IL-10, IL-1ß, TNF-α and IL-6, restored the levels of ALT, AST, r-GT, AKP and TBA in vivo, and attenuated isoniazid liver injury. Both in vivo and vitro results indicated that dill could regulate the expression of NAT2 enzymes. CONCLUSIONS: The results tentatively demonstrate that dill can alleviate isoniazid liver injury through multiple components, targets and pathways and exerts a regulatory effect on the NAT2 enzyme, and these findings thus provide new ideas for subsequent studies on hydrazide liver injury--reducing the risk of hydrazide-induced liver injury through anti-inflammation and regulation of NAT2 enzymes.
Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Medicamentos Herbarios Chinos , Ratas , Animales , Isoniazida/toxicidad , Medicina Tradicional China , Arabia Saudita , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11ß-hydroxyandrostenedione (11ß-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Próstata/metabolismo , Andrógenos/metabolismo , Andrógenos/farmacología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Antagonistas de Andrógenos/metabolismo , Antagonistas de Andrógenos/farmacología , Hidrocortisona/metabolismo , Hidrocortisona/farmacología , Línea Celular TumoralRESUMEN
With rapid advances in the development of metabolic pathways and synthetic biology toolkits, a persisting challenge in microbial bioproduction is how to optimally rewire metabolic fluxes and accelerate the concomitant high-throughput phenotype screening. Here we developed a biosensor-assisted titratable CRISPRi high-throughput (BATCH) screening approach that combines a titratable mismatch CRISPR interference and a biosensor mediated screening for high-production phenotypes in Escherichia coli. We first developed a programmable mismatch CRISPRi that could afford multiple levels of interference efficacy with a one-pot sgRNA pool (a total of 16 variants for each target gene) harboring two consecutive random mismatches in the seed region of sgRNA spacers. The mismatch CRISPRi was demonstrated to enable almost a full range of gene knockdown when targeting different positions on genes. As a proof-of-principle demonstration of the BATCH screening system, we designed doubly mismatched sgRNA pools targeting 20 relevant genes in E. coli and optimized a PadR-based p-coumaric acid biosensor with broad dynamic range for the eGFP fluorescence guided high-production screening. Using sgRNA variants for the combinatorial knockdown of pfkA and ptsI, the p-coumaric acid titer was increased by 40.6% to o 1308.6 mg/l from glycerol in shake flasks. To further demonstrate the general applicability of the BATCH screening system, we recruited a HpdR-based butyrate biosensor that facilitated the screening of E. coli strains achieving 19.0% and 25.2% increase of butyrate titer in shake flasks with sgRNA variants targeting sucA and ldhA, respectively. This work reported the establishment of a plug-and-play approach that enables multilevel modulation of metabolic fluxes and high-throughput screening of high-production phenotypes.
Asunto(s)
Escherichia coli , Ensayos Analíticos de Alto Rendimiento , Escherichia coli/genética , Escherichia coli/metabolismo , Ácidos Cumáricos , Fenotipo , Sistemas CRISPR-Cas/genética , Ingeniería MetabólicaRESUMEN
Establishing microbial cell factories has become a sustainable and increasingly promising approach for the synthesis of valuable chemicals. However, introducing heterologous pathways into these cell factories can disrupt the endogenous cellular metabolism, leading to suboptimal production performance. To address this challenge, dynamic pathway regulation has been developed and proven effective in improving microbial biosynthesis. In this review, we summarized typical dynamic regulation strategies based on their control logic. The applicable scenarios for each control logic were highlighted and perspectives for future research direction in this area were discussed.
RESUMEN
N6-methyladenosine (m6A) RNA modification plays important regulatory roles in plant development and adapting to the environment, which requires methyltransferases to achieve the methylation process. However, there has been no research regarding m6A RNA methyltransferases in cotton. Here, a systematic analysis of the m6A methyltransferase (METTL) gene family was performed on twelve cotton species, resulting in six METTLs identified in five allotetraploid cottons, respectively, and three to four METTLs in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that METTL genes from cottons, Arabidopsis thaliana, and Homo sapiens could be classified into three clades (METTL3, METTL14, and METTL-like clades). Cis-element analysis predicated the possible functions of METTL genes in G. hirsutum. RNA-seq data revealed that GhMETTL14 (GH_A07G0817/GH_D07G0819) and GhMETTL3 (GH_A12G2586/GH_D12G2605) had high expressions in root, stem, leaf, torus, petal, stamen, pistil, and calycle tissues. GhMETTL14 also had the highest expression in 20 and 25 dpa fiber cells, implying a potential role at the cell wall thickening stage. Suppressing GhMETTL3 and GhMETTL14 by VIGS caused growth arrest and even death in G. hirsutum, along with decreased m6A abundance from the leaf tissues of VIGS plants. Overexpression of GhMETTL3 and GhMETTL14 produced distinct differentially expressed genes (DEGs) in A. thaliana, indicating their possible divergent functions after gene duplication. Overall, GhMETTLs play indispensable but divergent roles during the growth of cotton plants, which provides the basis for the systematic investigation of m6A in subsequent studies to improve the agronomic traits in cotton.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Gossypium , Metiltransferasas , Humanos , Genómica , Gossypium/genética , Metiltransferasas/genética , Filogenia , ARNRESUMEN
BACKGROUND: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. METHODS: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. CONCLUSION: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.
Asunto(s)
Terapia por Acupuntura , Calidad de Vida , Terapia por Acupuntura/métodos , Disnea/etiología , Disnea/terapia , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
Rare earth fluorides have been widely used in recent years in the field of solid-state lighting. However, the relationship between the structure and luminescence properties is still unclear. Herein, the photoluminescence and structural transition of CeF3:Tb3+ nanoparticles under high pressure were investigated through in situ photoluminescence and X-ray diffraction measurements. Intriguingly, the photoluminescence of CeF3:Tb3+ nanoparticles displays an enhancement from 18.3 to 33.4 GPa, accompanied by the phase transition from the starting hexagonal phase to the orthorhombic phase. It was found that the distance of luminescent centers increased sharply during the high-pressure phase transition, which weakened the quenching effect and improved transmission efficiency. Our work provides more insight into the optical characteristics and structures of rare earth trifluorides.
RESUMEN
BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.
Asunto(s)
Síndrome de Brown-Séquard , Traumatismos de la Médula Espinal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Síndrome de Brown-Séquard/tratamiento farmacológico , Femenino , Flavonas , Ratas , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patologíaRESUMEN
The widely cultivated medicinal and ornamental plant sage (Salvia officinalis L.) is an evergreen shrub of the Lamiaceae family, native to the Mediterranean. We assembled a high-quality sage genome of 480 Mb on seven chromosomes, and identified a biosynthetic gene cluster (BGC) encoding two pairs of diterpene synthases (diTPSs) that, together with the cytochromes P450 (CYPs) genes located inside and outside the cluster, form two expression cascades responsible for the shoot and root diterpenoids, respectively, thus extending BGC functionality from co-regulation to orchestrating metabolite production in different organs. Phylogenomic analysis indicates that the Salvia clades diverged in the early Miocene. In East Asia, most Salvia species are herbaceous and accumulate diterpenoids in storage roots. Notably, in Chinese sage S. miltiorrhiza, the diterpene BGC has contracted and the shoot cascade has been lost. Our data provide genomic insights of micro-evolution of growth type-associated patterning of specialized metabolite production in plants.