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X-ray communication is a kind of space communication technology which uses X-ray as information carrier. In order to improve the information transmission capacity, communication rate and anti-interference ability of X-ray communication, we proposes to design a novel multi-target X-ray source. The source is composed of a fast switching module of light channels based on FPGA technology and four photoelectric X-ray tubes with different target materials: Cr, Fe, Ni, and Cu. Using Geant4 software, we determined the optimal target thickness for each material, which enabled us to fully leverage the characteristic X-rays for multi-channel signal modulation transmission. Moreover, using CST software for particle trajectory simulation and optimization of the electron beam revealed that at a tube voltage of 20 kV, the focus area measures approximately 1.2 mm×1.2 mm. The simulations show that four kinds of spectra with high distinctiveness can be generated from the Cr, Fe, Ni, and Cu targets. Within a single modulation period, these spectra can be combined in various ways to create 16 different X-ray spectra signals, thereby increasing the number of communication elements and enhancing the information transmission rate.
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Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.
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Envejecimiento , Amoníaco , Ácidos y Sales Biliares , Disfunción Cognitiva , Absorción Intestinal , Animales , Ácidos y Sales Biliares/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Absorción Intestinal/efectos de los fármacos , Masculino , Femenino , Humanos , Ratones , Envejecimiento/metabolismo , Amoníaco/metabolismo , Anciano , Ratones Endogámicos C57BL , Resina de Colestiramina/farmacología , Simportadores/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Hipocampo/metabolismo , Hipocampo/patología , Ratas , Anciano de 80 o más AñosRESUMEN
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.
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Depresión , Microbioma Gastrointestinal , Ácido Homovanílico , Ratones Endogámicos C57BL , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Depresión/tratamiento farmacológico , Depresión/metabolismo , Masculino , Humanos , Ácido Homovanílico/metabolismo , Sinapsis/metabolismo , Sinapsis/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , FemeninoRESUMEN
Expansion of a G4C2 repeat in the C9orf72 gene is associated with familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). To investigate the underlying mechanisms of repeat instability, which occurs both somatically and intergenerationally, we created a novel mouse model of familial ALS/FTD that harbors 96 copies of G4C2 repeats at a humanized C9orf72 locus. In mouse embryonic stem cells, we observed two modes of repeat expansion. First, we noted minor increases in repeat length per expansion event, which was dependent on a mismatch repair pathway protein Msh2. Second, we found major increases in repeat length per event when a DNA double- or single-strand break (DSB/SSB) was artificially introduced proximal to the repeats, and which was dependent on the homology-directed repair (HDR) pathway. In mice, the first mode primarily drove somatic repeat expansion. Major changes in repeat length, including expansion, were observed when SSB was introduced in one-cell embryos, or intergenerationally without DSB/SSB introduction if G4C2 repeats exceeded 400 copies, although spontaneous HDR-mediated expansion has yet to be identified. These findings provide a novel strategy to model repeat expansion in a non-human genome and offer insights into the mechanism behind C9orf72 G4C2 repeat instability.
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Proteína C9orf72 , Expansión de las Repeticiones de ADN , Inestabilidad Genómica , Animales , Humanos , Ratones , Esclerosis Amiotrófica Lateral/genética , Proteína C9orf72/genética , Modelos Animales de Enfermedad , Roturas del ADN de Doble Cadena , Expansión de las Repeticiones de ADN/genética , Demencia Frontotemporal/genética , Técnicas de Sustitución del Gen , Inestabilidad Genómica/genética , Proteína 2 Homóloga a MutS/genéticaRESUMEN
Attention and memory are fundamental cognitive processes that closely interact. In the attentional boost effect (ABE), the stimuli that co-occur with targets are remembered better than those that co-occur with distractors in target detection tasks performed during memory encoding. In target detection tasks performed during retrieval, the stimuli that co-occur with targets are recognized as 'old' more easily than the stimuli that co-occur with distractors. This study mainly explored the internal mechanism of the effect of target detection on recognition. In Experiment 1, the full attention (FA; where participants performed only the memory task) condition was used to compare with divided attention (DA; where participants performed target detection while performing memory retrieval) condition to explore the impact of target detection and distraction inhibition on recognition. In Experiment 2, the proportion of old and new words in the retrieval stage was adjusted to 1:1 to eliminate the possible reaction tendency caused by the high proportion of old words. In Experiment 3, the presentation time of words was extended to 1.5 s and 3 s to eliminate the possible impact of rapid processing. The results indicated that the effect of target detection on recognition was attributed to both target detection and distraction rejection and is not affected by the ratio of old and new words and the word presentation time. The effect of target detection on recognition may be owing to temporal yoking of the dual tasks, which is different from the effect of target detection on memory encoding.
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Atención , Recuerdo Mental , Reconocimiento Visual de Modelos , Tiempo de Reacción , Reconocimiento en Psicología , Humanos , Reconocimiento Visual de Modelos/fisiología , Masculino , Adulto Joven , Femenino , Inhibición Psicológica , Semántica , Adulto , Aprendizaje VerbalRESUMEN
The inducible CRISPR activation (CRISPR-a) system offers unparalleled precision and versatility for regulating endogenous genes, making it highly sought after in plant research. In this study, we developed a chemically inducible CRISPR-a tool for plants called ER-Tag by combining the LexA-VP16-ER inducible system with the SunTag CRISPR-a system. We systematically compared different induction strategies and achieved high efficiency in target gene activation. We demonstrated that guide RNAs can be multiplexed and pooled for large-scale screening of effective morphogenic genes and gene pairs involved in plant regeneration. Further experiments showed that induced activation of these morphogenic genes can accelerate regeneration and improve regeneration efficiency in both eudicot and monocot plants, including alfalfa, woodland strawberry, and sheepgrass. Our study expands the CRISPR toolset in plants and provides a powerful new strategy for studying gene function when constitutive expression is not feasible or ideal.
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Regeneración , Regeneración/genética , Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Plantas Modificadas Genéticamente/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Non-coding RNAs play vital roles in the diverse biological processes of plants, and they are becoming key topics in horticulture research. In particular, miRNAs and long non-coding RNAs (lncRNAs) are receiving increased attention in fruit crops. Recent studies in horticulture research provide both genetic and molecular evidence that miRNAs and lncRNAs regulate biological function and stress responses during fruit development. Here, we summarize multiple regulatory modules of miRNAs and lncRNAs and their biological roles in fruit sets and stress responses, which would guide the development of molecular breeding techniques on horticultural crops.
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Healing of an anterior cruciate ligament (ACL) autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue, which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence. In this study, an injectable hydroxyapatite/type I collagen (HAp/Col â ) paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface. Physicochemical characterization demonstrated that the HAp/Col â paste was injectable, uniform and stable. The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression. The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL. The average width of the tunnel, total bone volume, bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group. The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL's maximal load at 24 weeks. According to histological examination, Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group. The injectable HAp/Col â paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation, further osteogenic expression and extracellular matrix deposition, and in vivo structural and functional regeneration of the tendon-bone interface.
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There is a relationship between lung injury and ulcerative colitis. Currently, traditional Chinese medicine (Huangqi Jiegeng (HQJGD) and Huangqi Huanglian decoctions (HQHLD)) is commonly used for UC-related lung injury; however, the mechanisms of these drugs remain unclear. In this study, UC models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 4 weeks. The pathological changes in the lung, intestine, liver, and kidney were observed; cytokines, chemokines, and adhesion molecules in lung tissue were detected in order to explore the immunological mechanism of UC-related lung injury and the intervention mechanism of traditional Chinese medicine in treating the lung and intestine in the immune-TNBS-ethanol rat model. Histology examinations demonstrated evident pathological changes in the lungs and intestines of the model groups. Furthermore, all groups treated with TCMs demonstrated reduced expressions of toll-like receptor 4, nuclear factor kappa-B, and macrophage migration inhibitory factor. Additionally, radioimmunoassay and immunohistochemistry showed tumor necrosis factor-α, interleukin-6, and 8 expression downregulation. The results showed that HQJGD and HQHLD could alleviate pulmonary inflammation in UC-related lung injury by obviously improving the pathology and fibrosis of the lung, inhibiting the positive feedback loop of MIF/NF-κB, and reducing lymphocyte homing to bronchial mucosa. This model revealed the immune mechanism of UC-related lung injury and the intervention mechanism of the Chinese medicine, which provided the rationale for treating ulcerative colitis clinically, so as to demonstrate the theory of "the lung and the large intestine being interior-exteriorly related" and "treating the same disease with different approaches."
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Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.
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Microbioma Gastrointestinal , Animales , Bacteroidetes , Ácidos y Sales Biliares , Restricción Calórica , Dieta Alta en Grasa/efectos adversos , Microbioma Gastrointestinal/fisiología , Ratones , Ratones Endogámicos C57BL , Aumento de PesoRESUMEN
BACKGROUND: As a common postoperative complication to elderly patients, postoperative cognitive dysfunction (POCD) is a central nervous system complication, often taking place after anesthesia and surgery. (Su(var)3-9, enhancer-of-zeste, and trithorax) domain-containing protein 7 (SETD7) plays important roles in metabolic-related diseases, viral infections, tumor formation, and some inflammatory reactions. However, the role and mechanism of SETD7 in POCD have not been previously studied. METHODS: RT-PCR and Western blot were performed to evaluate the efficiency of knockdown of SETD7. The pathological changes of hippocampal neurons in isoflurane-anesthetized mice were detected by HE staining, and the Morris water maze experiment was performed to evaluate the learning and memory abilities of mice. The effect of SETD7 on the hippocampus in isoflurane-induced aged mice was examined by Western blot and TUNEL assay. Then ELISA assay was applied to determine the expression of some inflammatory cytokines, followed by the detection of expression of NOD-like receptor protein 3 (NLRP3) inflammasome through Western blot. RESULTS: The data of this research revealed that SETD7 knockdown improved cognitive impairment in isoflurane-anesthetized mice, ameliorated cell pyroptosis, inhibited the release of inflammatory cytokines, and suppressed the activation of NLRP3 inflammasome in the hippocampus in isoflurane-induced aged mice. CONCLUSION: Collectively, these results provided evidence that the inhibition of SETD7 could alleviate neuroinflammation, pyroptosis, and cognitive impairment by suppressing the activation of the NLRP3 inflammasome in isoflurane-induced aged mice.
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Anestésicos por Inhalación/efectos adversos , Técnicas de Silenciamiento del Gen , Inflamasomas/metabolismo , Metiltransferasas/metabolismo , Proteínas NLR/metabolismo , Dominios PR-SET/genética , Complicaciones Cognitivas Postoperatorias/inducido químicamente , Envejecimiento/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Inflamasomas/genética , Isoflurano/efectos adversos , Masculino , Metiltransferasas/genética , Ratones , Proteínas NLR/genéticaRESUMEN
The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field, such as collagen or hyaluronic acid, etc. However, the biosafety and efficacy of these implants are still challenged. In this study, a skin damage animal model was prepared by UV-photoaging and recombinant humanized type III collagen (rhCol III) was applied as a bioactive material to implant in vivo to study its biological effect, comparing with saline and uncrosslinked hyaluronic acid (HA). Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment. Histological observation, specific gene expression and other molecular biological methods were applied by the end of the animal experiment. The results indicated that rhCol III could alleviate the skin photoaging caused by UV radiation, including reduce the thickening of epidermis and dermis, increase the secretion of Collagen I (Col I) and Collagen III (Col III) and remodel of extracellular matrix (ECM). Although the cell-material interaction and mechanism need more investigation, the effect of rhCol III on damaged skin was discussed from influence on cells, reconstruction of ECM, and stimulus of small biological molecules based on current results. In conclusion, our findings provided rigorous biosafety information of rhCol III and approved its potential in skin repair and regeneration. Although enormous efforts still need to be made to achieve successful translation from bench to clinic, the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.
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Background: The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery. Methods: Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan-Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS. Results: A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan-Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort. Conclusions: The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.
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Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 1019) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 × 105). B4GALT1 genebased analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease.
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LDL-Colesterol/sangre , Fibrinógeno/análisis , Galactosiltransferasas/genética , Mutación Missense , Animales , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/prevención & control , Femenino , Galactosa/metabolismo , Galactosiltransferasas/metabolismo , Técnicas de Sustitución del Gen , Técnicas de Silenciamiento del Gen , Glicoproteínas/sangre , Glicosilación , Humanos , Hígado/enzimología , Masculino , Ratones , Ácido N-Acetilneuramínico/metabolismo , Polisacáridos/sangre , Secuenciación Completa del GenomaRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the colon. The aim of the present study was to explore the effects of leonurine (YMJ) on inflammation and intestinal microflora in colonic tissues of a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Mice were randomly divided into control (n=5), DSS (n=5, treated with DSS) and DSS+YMJ (n=5, treated with DSS and YMJ) groups. Body weight was recorded, disease activity index (DAI) was calculated, and colon histopathology was evaluated using hematoxylin and eosin staining. Serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1ß levels were examined using ELISA. Expression levels of nuclear factor-κB (p65) and phosphorylated (p)-p65 were evaluated via western blotting. 16S ribosomal RNA was extracted from mouse feces. Composition or abundance changes of intestinal microflora were analyzed. The results indicated that YMJ treatment (DSS+YMJ group) significantly increased body weight, reduced DAI scores and increased colon length in UC mouse models compared with those in the DSS group (P<0.05). YMJ significantly reduced inflammatory infiltration, significantly decreased serum TNF-α, IL-6 and IL-1ß levels (P<0.05) and significantly downregulated the p-p65/p65 ratio compared with the DSS group (P<0.05). YMJ increased the quantity of the intestinal flora and improved intestinal microflora diversity in the mice of the DSS group. Specifically, YMJ partly regulated intestinal microflora in feces, including a reduction of Bifidobacterium, and an increase in Parasutterella and Ackermania. In conclusion, YMJ improved disease outcomes of the UC mice, reduced the levels of serum inflammatory factors and increased the ratio of beneficial bacteria in the intestinal tract.
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Lysosomal diseases are a class of genetic disorders predominantly caused by loss of lysosomal hydrolases, leading to lysosomal and cellular dysfunction. Enzyme replacement therapy (ERT), where recombinant enzyme is given intravenously, internalized by cells, and trafficked to the lysosome, has been applied to treat several lysosomal diseases. However, current ERT regimens do not correct disease phenotypes in all affected organs because the biodistribution of enzyme uptake does not match that of the affected cells that require the enzyme. We present here targeted ERT, an approach that utilizes antibody-enzyme fusion proteins to target the enzyme to specific cell types. The antibody moiety recognizes transmembrane proteins involved in lysosomal trafficking and that are also preferentially expressed in those cells most affected in disease. Using Pompe disease (PD) as an example, we show that targeted ERT is superior to ERT in treating the skeletal muscle phenotypes of PD mice both as a protein replacement therapeutic and as a gene therapy.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Enfermedades por Almacenamiento Lisosomal , Animales , Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Hidrolasas/metabolismo , Enfermedades por Almacenamiento Lisosomal/tratamiento farmacológico , Enfermedades por Almacenamiento Lisosomal/genética , Lisosomas/metabolismo , Ratones , Distribución Tisular , alfa-Glucosidasas/genéticaRESUMEN
Tissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR+ IELs, however, the mechanisms that control γδ IEL maintenance within discrete intestinal segments are unclear. Here, we show that Btnl2 suppressed homeostatic proliferation of γδ IELs preferentially in the ileum. High throughput transcriptomic characterization of site-specific Btnl2-KO γδ IELs reveals that Btnl2 regulated the antimicrobial response module of ileal γδ IELs. Btnl2 deficiency shapes the TCR specificities and TCRγ/δ repertoire diversity of ileal γδ IELs. During DSS-induced colitis, Btnl2-KO mice exhibit increased inflammation and delayed mucosal repair in the colon. Collectively, these data suggest that Btnl2 fine-tunes γδ IEL frequencies and TCR specificities in response to site-specific homeostatic and inflammatory cues. Hence, Btnl-mediated targeting of γδ IEL development and maintenance may help dissect their immunological functions in intestinal diseases with segment-specific manifestations.
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Butirofilinas/genética , Íleon/inmunología , Inmunidad Innata/genética , Inmunidad Mucosa/genética , Linfocitos Intraepiteliales/metabolismo , Animales , Butirofilinas/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Allergic rhinitis is a global problem. About 10% to 40% of the global population is affected by allergic rhinitis and is on the rise, which has a significant health and economic impact on society. Ear acupuncture is a non-invasive acupuncture therapy, which has been used in the treatment of allergic rhinitis, and some positive results have been reported, but there is not enough evidence to prove its efficacy and safety. METHODS: This is a single-center, randomized, single-blind, sham-controlled trial. With the approval of the ethics committee of our hospital, participants with allergic rhinitis will be randomly assigned to receive either real or sham ear acupuncture once a week for 8âweeks, followed by 12âweeks of follow-up. Evaluate the patient's nasal symptom score and Standardised Rhinoconjunctivitis Quality of Life Questionnaire score, and monitor adverse events. Finally, the data are analyzed by SPSS 22.0 software. DISCUSSION: The results of this study will determine the efficacy and safety of ear acupuncture in the treatment of allergic rhinitis and provide a basis for promoting the application of ear acupuncture in the treatment of allergic rhinitis. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/MVEF7.
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Acupuntura Auricular , Rinitis Alérgica/terapia , Acupuntura Auricular/efectos adversos , Humanos , Estudios Prospectivos , Calidad de Vida , Rinitis Alérgica/psicología , Método Simple Ciego , Resultado del TratamientoRESUMEN
Long noncoding RNAs (lncRNAs) are emerging as important regulators in plant development, but few of them have been functionally characterized in fruit ripening. Here, we have identified 25,613 lncRNAs from strawberry ripening fruits based on RNA-seq data from poly(A)-depleted libraries and rRNA-depleted libraries, most of which exhibited distinct temporal expression patterns. A novel lncRNA, FRILAIR harbours the miR397 binding site that is highly conserved in diverse strawberry species. FRILAIR overexpression promoted fruit maturation in the Falandi strawberry, which was consistent with the finding from knocking down miR397, which can guide the mRNA cleavage of both FRILAIR and LAC11a (encoding a putative laccase-11-like protein). Moreover, LAC11a mRNA levels were increased in both FRILAIR overexpressing and miR397 knockdown fruits, and accelerated fruit maturation was also found in LAC11a overexpressing fruits. Overall, our study demonstrates that FRILAIR can act as a noncanonical target mimic of miR397 to modulate the expression of LAC11a in the strawberry fruit ripening process.
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Fragaria/crecimiento & desarrollo , Fragaria/genética , Frutas/genética , Regulación de la Expresión Génica de las Plantas , ARN Largo no Codificante , ARN de Planta , Edición Génica , Estudios de Asociación Genética , MicroARNs/genética , Modelos Biológicos , Fenotipo , ARN Guía de Kinetoplastida , ARN Mensajero/genéticaRESUMEN
Neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G > A (p.Arg128Gln), c.520G > T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.