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1.
bioRxiv ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38948808

RESUMEN

Background: Emerging studies in humans have established the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) over primary somatosensory cortex (S1) on somatosensory cortex activity and perception. However, to date, research in this area has primarily focused on the hand and fingers, leaving a gap in our understanding of the modulatory effects of rTMS on somatosensory perception of the orofacial system and speech articulators. Objective: The present study aimed to examine the effects of different types of theta-burst stimulation-continuous TBS (cTBS), intermittent TBS (iTBS), or sham-over the tongue representation of left S1 on tactile acuity of the tongue. Methods: In a repeated-measures design, fifteen volunteers participated in four separate sessions, where cTBS, iTBS, sham, or no stimulation was applied over the tongue representation of left S1. Effects of TBS were measured on both temporal and spatial perceptual acuity of tongue using a custom vibrotactile stimulator. Results: CTBS significantly impaired spatial amplitude threshold at the time window of 16-30 minutes after stimulation, while iTBS improved it at the same time window. The effect of iTBS, however, was smaller than cTBS. In contrast, neither cTBS nor iTBS had any effect on the temporal discrimination threshold. Conclusions: The current study establishes the validity of using TBS to modulate somatosensory perception of the orofacial system. Directly modifying somatosensation in the orofacial system has the potential to benefit clinical populations with abnormal tactile acuity, improve our understanding of the role of sensory systems in speech production, and enhance speech motor learning and rehabilitation. Highlights: Theta-burst stimulation (TBS) can modulate somatosensation in the orofacial systemcTBS over S1 impaired spatial acuity of tongueiTBS over S1 improved spatial acuity of tongue.

2.
Neurobiol Lang (Camb) ; 5(2): 454-483, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911464

RESUMEN

Hearing one's own speech allows for acoustic self-monitoring in real time. Left-hemisphere motor planning regions are thought to give rise to efferent predictions that can be compared to true feedback in sensory cortices, resulting in neural suppression commensurate with the degree of overlap between predicted and actual sensations. Sensory prediction errors thus serve as a possible mechanism of detection of deviant speech sounds, which can then feed back into corrective action, allowing for online control of speech acoustics. The goal of this study was to assess the integrity of this detection-correction circuit in persons with aphasia (PWA) whose left-hemisphere lesions may limit their ability to control variability in speech output. We recorded magnetoencephalography (MEG) while 15 PWA and age-matched controls spoke monosyllabic words and listened to playback of their utterances. From this, we measured speaking-induced suppression of the M100 neural response and related it to lesion profiles and speech behavior. Both speaking-induced suppression and cortical sensitivity to deviance were preserved at the group level in PWA. PWA with more spared tissue in pars opercularis had greater left-hemisphere neural suppression and greater behavioral correction of acoustically deviant pronunciations, whereas sparing of superior temporal gyrus was not related to neural suppression or acoustic behavior. In turn, PWA who made greater corrections had fewer overt speech errors in the MEG task. Thus, the motor planning regions that generate the efferent prediction are integral to performing corrections when that prediction is violated.

3.
Elife ; 132024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864853

RESUMEN

Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Emparejamiento Cromosómico , Meiosis , Oryza , Meiosis/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Oryza/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Cohesinas , Mitosis , Complejo Sinaptonémico/metabolismo , Complejo Sinaptonémico/genética , Sistemas CRISPR-Cas
4.
Front Hum Neurosci ; 18: 1364803, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567000

RESUMEN

Human speech production is strongly influenced by the auditory feedback it generates. Auditory feedback-what we hear when we speak-enables us to learn and maintain speaking skills and to rapidly correct errors in our speech. Over the last three decades, the real-time altered auditory feedback (AAF) paradigm has gained popularity as a tool to study auditory feedback control during speech production. This method involves changing a speaker's speech and feeding it back to them in near real time. More than 50% of the world's population speak tonal languages, in which the pitch or tone used to pronounce a word can change its meaning. This review article aims to offer an overview of the progression of AAF paradigm as a method to study pitch motor control among speakers of tonal languages. Eighteen studies were included in the current mini review and were compared based on their methodologies and results. Overall, findings from these studies provide evidence that tonal language speakers can compensate and adapt when receiving inconsistent and consistent pitch perturbations. Response magnitude and latency are influenced by a range of factors. Moreover, by combining AAF with brain stimulation and neuroimaging techniques, the neural basis of pitch motor control in tonal language speakers has been investigated. To sum up, AAF has been demonstrated to be an emerging tool for studying pitch motor control in speakers of tonal languages.

5.
Plant Physiol ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38478471

RESUMEN

During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends towards the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.

6.
Plant Commun ; 5(6): 100857, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38433446

RESUMEN

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.


Asunto(s)
Meiosis , Mitosis , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Meiosis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Citocininas/metabolismo
7.
Emerg Microbes Infect ; 13(1): 2332669, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38494777

RESUMEN

Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.


Asunto(s)
Mpox , Vacunas , Animales , Humanos , Monkeypox virus/genética , Antivirales/farmacología , Macaca
8.
Sensors (Basel) ; 23(21)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37960593

RESUMEN

Reliable quality control of laser welding on power batteries is an important issue due to random interference in the production process. In this paper, a quality inspection framework based on a two-branch network and conventional image processing is proposed to predict welding quality while outputting corresponding parameter information. The two-branch network consists of a segmentation network and a classification network, which alleviates the problem of large training sample size requirements for deep learning by sharing feature representations among two related tasks. Moreover, coordinate attention is introduced into feature learning modules of the network to effectively capture the subtle features of defective welds. Finally, a post-processing method based on the Hough transform is used to extract the information of the segmented weld region. Extensive experiments demonstrate that the proposed model can achieve a significant classification performance on the dataset collected on an actual production line. This study provides a valuable reference for an intelligent quality inspection system in the power battery manufacturing industry.

9.
Plant J ; 116(3): 717-727, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37632767

RESUMEN

Crossovers (COs) are necessary for generating genetic diversity that breeders can select, but there are conserved mechanisms that regulate their frequency and distribution. Increasing CO frequency may raise the efficiency of selection by increasing the chance of integrating more desirable traits. In this study, we characterize rice FANCM and explore its functions in meiotic CO control. FANCM mutations do not affect fertility in rice, but they cause a great boost in the overall frequency of COs in both inbred and hybrid rice, according to genetic analysis of the complete set of fancm zmm (hei10, ptd, shoc1, mer3, zip4, msh4, msh5, and heip1) mutants. Although the early homologous recombination events proceed normally in fancm, the meiotic extra COs are not marked with HEI10 and require MUS81 resolvase for resolution. FANCM depends on PAIR1, COM1, DMC1, and HUS1 to perform its functions. Simultaneous disruption of FANCM and MEICA1 synergistically increases CO frequency, but it is accompanied by nonhomologous chromosome associations and fragmentations. FANCM interacts with the MHF complex, and ablation of rice MHF1 or MHF2 could restore the formation of 12 bivalents in the absence of the ZMM gene ZIP4. Our data indicate that unleashing meiotic COs by mutating any member of the FANCM-MHF complex could be an effective procedure to accelerate the efficiency of rice breeding.


Asunto(s)
Oryza , Oryza/genética , ADN Helicasas/genética , Fitomejoramiento , Meiosis/genética , Recombinación Homóloga , Intercambio Genético
10.
Front Immunol ; 14: 1203410, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37435062

RESUMEN

Since May 2022, mutant strains of mpox (formerly monkeypox) virus (MPXV) have been rapidly spreading among individuals who have not traveled to endemic areas in multiple locations, including Europe and the United States. Both intracellular and extracellular forms of mpox virus have multiple outer membrane proteins that can stimulate immune response. Here, we investigated the immunogenicity of MPXV structural proteins such as A29L, M1R, A35R, and B6R as a combination vaccine, and the protective effect against the 2022 mpox mutant strain was also evaluated in BALB/c mice. After mixed 15 µg QS-21 adjuvant, all four virus structural proteins were administered subcutaneously to mice. Antibody titers in mouse sera rose sharply after the initial boost, along with an increased capacity of immune cells to produce IFN-γ alongside an elevated level of cellular immunity mediated by Th1 cells. The vaccine-induced neutralizing antibodies significantly inhibited the replication of MPXV in mice and reduced the pathological damage of organs. This study demonstrates the feasibility of a multiple recombinant vaccine for MPXV variant strains.


Asunto(s)
Mpox , Vacuna contra Viruela , Animales , Ratones , Ratones Endogámicos BALB C , Mpox/prevención & control , Monkeypox virus , Proteínas Recombinantes , Vacunación
11.
Phytomedicine ; 115: 154837, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37126969

RESUMEN

BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease, which seriously affects the sufferers' life quality and increases the socioeconomic burden. Guominkang (GMK), a well-known prescription for AR treatment, showed satisfactory effects; while its anti-allergic components remain to be disclosed. AlGaN/GaN HEMT biochip is more sensitive and cost-effective than other binding equipments, indicating its great potential for screening of active ingredients from herbal medicines. METHODS: AR mouse models were first established to test the anti-allergic effect of GMK and discover the ingredients absorbed into blood by ultra-high performance liquid chromatography-mass spectra (UHPLC-MS). Then, novel Syk/Lyn/Fyn-functionalized high electron mobility transistor (HEMT) biochips with high sensitivity and specificity were constructed and applied to screen the active components. Finally, the results from HEMT biochips screening were validated via in silico (molecular docking and molecular dynamics simulation), in vitro (RBL-2H3 cells), and in vivo (PCA mice model) assays. RESULTS: GMK showed a potent therapeutic effect on AR mice, and fifteen components were identified from the medicated plasma. Furthermore, hamaudol was firstly found to selectively inhibit the Syk and Lyn, and emodin was to selectively inhibit Lyn, which were further confirmed by isothermal titration calorimetry, molecular docking, and molecular dynamics simulation analyses. Suppression of the activation of FcεRI-MAPK signals might be the possible mechanism of the anti-allergic effect of hamaudol. CONCLUSIONS: The targets of emodin and hamaudol were discovered by HEMT biochips for the first time. This study provided a novel and effective strategy to discover active components in a complex herbal formula by using AlGaN/GaN HEMT biochips.


Asunto(s)
Antialérgicos , Emodina , Rinitis Alérgica , Ratones , Animales , Antialérgicos/farmacología , Simulación del Acoplamiento Molecular , Emodina/farmacología , Rinitis Alérgica/tratamiento farmacológico , Modelos Animales de Enfermedad
12.
Plant Physiol ; 192(2): 1063-1079, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-36905369

RESUMEN

Centromeres consist of highly repetitive sequences that are challenging to map, clone, and sequence. Active genes exist in centromeric regions, but their biological functions are difficult to explore owing to extreme suppression of recombination in these regions. In this study, we used the CRISPR/Cas9 system to knock out the transcribed gene Mitochondrial Ribosomal Protein L15 (OsMRPL15), located in the centromeric region of rice (Oryza sativa) chromosome 8, resulting in gametophyte sterility. Osmrpl15 pollen was completely sterile, with abnormalities appearing at the tricellular stage including the absence of starch granules and disrupted mitochondrial structure. Loss of OsMRPL15 caused abnormal accumulation of mitoribosomal proteins and large subunit rRNA in pollen mitochondria. Moreover, the biosynthesis of several proteins in mitochondria was defective, and expression of mitochondrial genes was upregulated at the mRNA level. Osmrpl15 pollen contained smaller amounts of intermediates related to starch metabolism than wild-type pollen, while biosynthesis of several amino acids was upregulated, possibly to compensate for defective mitochondrial protein biosynthesis and initiate consumption of carbohydrates necessary for starch biosynthesis. These results provide further insight into how defects in mitoribosome development cause gametophyte male sterility.


Asunto(s)
Oryza , Oryza/genética , Oryza/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Genes de Plantas , Almidón/metabolismo , Polen/genética , Polen/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
Protoplasma ; 260(5): 1313-1325, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36918417

RESUMEN

During the growth of Pinellia ternata (Thunb.) Breit. (P. ternata), the violet-red skin was occasionally produced spontaneously under natural cultivation. However, the specific mechanism leading to the color change is still unclear. This study performed transcriptomes in violet-red and pale-yellow skin and their peeled tubers of P. ternata, and the total flavonoids and anthocyanin contents were also determined. The results showed that the majority of genes involved in anthocyanin production were considerably increased in the violet-red skin of P. ternata tuber compared to the pale-yellow skin. Especially, phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) showed a remarkable increase in gene expression levels. Notably, shikimate O-hydroxycinnamoyltransferase (HCT), naringenin 3-dioxygenase (F3H), flavanone 4-reductase (DFR), and anthocyanidin synthase (ANS) were explicitly expressed in violet-red skin of P. ternata tuber, while undetectable in pale-yellow skin. The upregulation of these genes may explain the accumulation of anthocyanins, which forms the violet-red skin of P. ternata tuber. The transcription factors, including C2H2, bZIP, ERF, GATA, bHLH, C3H, NAC, MYB-related, and MYB families, might trigger the skin color change in P. ternata. The entire anthocyanin content in the violet-red skin of P. ternata tuber was 71.10 µg/g, and pale-yellow skin was 7.74 µg/g. According to phenotypic and transcriptome results, the elevated expression levels of genes linked to the synthesis of anthocyanins considerably contributed to the violet-red skin alterations in P. ternata tuber. This study provides a new understanding of the formation of the violet-red skin, lays a theoretical foundation for the cultivation of unique varieties of P. ternata, and provides transcriptome data for further study of the differences between different colors of P. ternata.


Asunto(s)
Antocianinas , Pinellia , Humanos , Antocianinas/genética , Antocianinas/metabolismo , Pinellia/genética , Pinellia/metabolismo , Perfilación de la Expresión Génica , Transcriptoma/genética , Genes Reguladores , Regulación de la Expresión Génica de las Plantas
14.
Exp Brain Res ; 241(4): 951-977, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36949150

RESUMEN

Over the last three decades, transcranial magnetic stimulation (TMS) has gained popularity as a tool to modulate human somatosensation. However, the effects of different stimulation types on the multiple distinct subdomains of somatosensation (e.g., tactile perception, proprioception and pain) have not been systematically compared. This is especially notable in the case of newer theta-burst stimulation protocols now in widespread use. Here, we aimed to systematically and critically review the existing TMS literature and provide a complete picture of current knowledge regarding the role of TMS in modulating human somatosensation across stimulation protocols and somatosensory domains. Following the PRISMA guidelines, fifty-four studies were included in the current review and were compared based on their methodologies and results. Overall, findings from these studies provide evidence that different types of somatosensation can be both disrupted and enhanced by targeted stimulation of specific somatosensory areas. Some mixed results, however, were reported in the literature. We discussed possible reasons for these mixed results, methodological limitations of existing investigations, and potential avenues for future research.


Asunto(s)
Percepción del Tacto , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Corteza Somatosensorial/fisiología , Percepción del Tacto/fisiología , Dolor
15.
Nano Lett ; 23(3): 757-764, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36648291

RESUMEN

Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized formulation performed feasible CRISPR-mediated downregulation of the target protein and reduction in the downstream cholesterol. As the first oral CRISPR carrier, this study suggests the potential of addressing the needs of both local and systemic editing in a patient-compliant manner.


Asunto(s)
Ácidos Borónicos , Quitosano , Animales , Ratones , Polímeros , Técnicas de Transferencia de Gen
16.
Molecules ; 28(2)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36677660

RESUMEN

The direct and rapid determination of trace cobalt ion (Co2+) in the electrolyte of zinc smelting plants is urgently needed but is impeded by the severe interference of extremely high-concentration zinc ions in the solution. Herein, colorimetric detection of Co2+ by the polyvinylpyrrolidone functionalized silver nanoparticles (PVP-AgNPs) is realized in solutions with the Zn/Co ratio being high, up to (0.8-5) × 104, which is located within the ratio range in industrial solution. The high concentration of Zn2+ induces a strong attenuation of Co2+-related signals in ultraviolet-visible (UV-vis) extinction spectra; nevertheless, a good linear range for detecting 1-6 mg/L Co2+ in 50 g/L Zn2+ solution is still acquired. The strong anti-interference toward other metal ions and the mechanism understanding for trace Co2+ detection in such a high-concentration Zn2+ solution are also revealed by systematic analysis techniques. The results extend the AgNPs as colorimetric sensors to industrial solutions, providing a new strategy for detecting trace-metal ions in industrial plants.

17.
Nat Prod Res ; 37(19): 3245-3252, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35437081

RESUMEN

Resina Draconis (RD), also known as 'dragon's blood', contains a broad range of natural compounds, such as flavonoids, stilbenes and dihydrochalcones. It is clinically used to enhance blood circulation. However, the major components of RD suffer from relatively poor water solubility. Glycosylation is a critical determinant for modulating solubility and improving bioavailability and bioactivity of natural products. Herein, we report a novel method to efficiently synthesize glycosidic derivatives of the major polyphenols in RD using a microbial glycosyltransferase, i.e., YjiC1. Solubility test showed that the synthetic glycosidic derivatives displayed higher water solubility than the raw materials. This research sheds light on the structural modification of natural products for higher water solubility, which is important for innovative drug discovery.

18.
New Phytol ; 237(6): 2422-2434, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36495065

RESUMEN

The endonuclease methyl methanesulfonate and UV-sensitive protein 81 (MUS81) has been reported to participate in DNA repair during mitosis and meiosis. However, the exact meiotic function of MUS81 in rice remains unclear. Here, we use a combination of physiological, cytological, and genetic approaches to provide evidence that MUS81 functions in atypical recombination intermediate resolution rather than crossover designation in rice. Cytological and genetic analysis revealed that the total chiasma numbers in mus81 mutants were indistinguishable from wild-type. The numbers of HEI10 foci (the sites of interference-sensitive crossovers) in mus81 were also similar to that of wild-type. Moreover, disruption of MUS81 in msh5 or msh4 msh5 background did not further decrease chiasmata frequency, suggesting that rice MUS81 did not function in crossover designation. Mutation of FANCM and ZEP1 could enhance recombination frequency. Unexpectedly, chromosome fragments and bridges were frequently observed in mus81 zep1 and mus81 fancm, illustrating that MUS81 may resolve atypical recombination intermediates. Taken together, our data suggest that MUS81 contributes little to crossover designation but plays a crucial role in the resolution of atypical meiotic intermediates by working together with other anti-crossover factors.


Asunto(s)
Intercambio Genético , Oryza , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Oryza/genética , Oryza/metabolismo , Meiosis/genética , Endonucleasas/genética , Endonucleasas/metabolismo
19.
Chin J Nat Med ; 20(12): 925-936, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36549806

RESUMEN

Guominkang (GMK), a Chinese medicine formula, has been used to treat allergic diseases in clinical settings for many years. To evaluate the antiallergic effect and molecular mechanism of action of GMK extract, RBL-2H3 cell models and passive cutaneous anaphylaxis (PCA) mouse models were established. High performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analyses were performed to characterize the chemical composition of GMK. A total of 94 compounds were identified or tentatively identified from GMK. Three of them, emodin, ursolic acid, and hamaudol, were identified for the first time as potential active compounds in GMK, since they inhibited the degranulation of mast cells. The anti-allergic effect of hamaudol was the first to be discovered. GMK could markedly mitigate the shade of Evans Blue extravasation and ear incrassation in PCA mouse models. Additionally, GMK significantly inhibited the degranulation of mast cells, suppressed mast cell degranulation by reducing Ca2+ influx and the levels of TNF-α, IL-4, and histamine, and markedly inhibited the phosphorylation of Lyn, Syk, PLCγ1, IκBα, and NF-κB p65. Molecular docking results indicated that hamaudol and emodin had strong interaction with FcɛRI and NF-κB related proteins, while ursolic acid only interacted with NF-κB associated proteins. These results suggest GMK suppresses the activation of MCs both in vivo and in vitro. The underlying mechanism of its anti-allergic activity is associated with the inhibition of FcɛRI and NF-κB activation.


Asunto(s)
Antialérgicos , Emodina , Ratones , Animales , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Inmunoglobulina E , FN-kappa B/genética , FN-kappa B/metabolismo , Anafilaxis Cutánea Pasiva , Mastocitos/metabolismo , Emodina/metabolismo , Simulación del Acoplamiento Molecular , Ácido Ursólico
20.
Sci Rep ; 12(1): 18765, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335171

RESUMEN

Eucommia ulmoides staminate flowers (EUF), a newly approved functional food in China, have great potential for hormonal regulation. Herein, we aim to demonstrate the chemical composition and pharmacological activity of EUF in testosterone production and hormonal regulation. EUF extract and its components, kaempferol and geniposidic acid, exhibited a strong stimulating effect by increasing testosterone secretion, reducing ROS production, or promoting viability in Leydig cells. Meanwhile, the increased testosterone production was related to the upregulation of mRNA and protein expression of the steroidogenic pathway, such as steroidogenic acute-regulatory protein (StAR), 3ß -hydroxysteroid dehydrogenase type 1 (HSD3B1), 17α-hydroxylase/17,20-lyase (CYP17A1), and nuclear receptor subfamily 5 group A member 1 (NR5A1). However, PKA inhibitor H89 or adenylyl cyclase inhibitor SQ22536 could block their effect. The results of transgenic yeast models showed the androgenic agonistic effects of kaempferol and naringenin and the estrogenic agonistic effects of rutin. These results indicated that the testosterone promotional effect of EUF was related to the activation of the steroidogenic pathway and potential hormonal regulation. Kaempferol and geniposidic acid might be the key active ingredients.


Asunto(s)
Eucommiaceae , Testosterona , Testosterona/metabolismo , Quempferoles/farmacología , Quempferoles/metabolismo , Células Intersticiales del Testículo/metabolismo , Andrógenos/metabolismo , Flores
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