RESUMO
OBJECTIVE: To evaluate the efficacy and safety of transcranial direct current stimulation in poststroke patients with upper extremity motor dysfunction using a systematic review and meta-analysis. DATA SOURCES: We searched the Web of Science, Cochrane Library, EMBASE, and PubMed for randomized controlled trials investigating the effects of both active and sham stimulation up until January 27, 2024. REVIEW METHODS: Efficacy, including the upper extremity Fugl-Meyer Assessment, Action Research Arm Test, Barthel Index, and safety, were assessed. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool and the Physiotherapy Evidence Database Scale. Meta-analysis was performed using the RevMan 5.4 software. RESULTS: Forty-four studies with 1555 participants were included. Transcranial direct current stimulation proved effective in improving upper extremity motor function (standardized mean difference = 0.22, 95% confidence interval: 0.12-0.32, P < 0.001) and Barthel Index (mean difference = 4.65, 95% confidence interval: 2.82-6.49, P < 0.001). Subgroup analysis revealed the highest transcranial direct current stimulation efficacy in patients with subacute stroke. Both anodal and cathodal stimulation were effective against upper extremity motor dysfunction. C3/C4 was the most effective stimulus target. Optimal stimulation parameters included stimulus current densities <0.057â mA/cm2 for 20-30â min and <30 sessions. Adverse effects and dropouts during follow-up showed that transcranial direct current stimulation is safe and feasible. CONCLUSIONS: Our findings suggest that both anodal and cathodal stimulation were significantly effective in subacute stroke patients, particularly when preceding other treatments and when C3/C4 is targeted.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Extremidade Superior , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Extremidade Superior/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Recuperação de Função Fisiológica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Parthenogenesis, the development of unfertilized egg cells into embryos, is a key component of apomixis. AtBBM (BABY BOOM), a crucial regulator of embryogenesis in Arabidopsis, possesses the capacity to shift nutritional growth toward reproductive growth. However, the mechanisms underlying AtBBM-induced parthenogenesis remain largely unexplored in dicot plants. Our findings revealed that in order to uphold the order of sexual reproduction, the embryo-specific promoter activity of AtBBM as well as repressors that inhibit its expression in egg cells combine to limiting its ability to induce parthenogenesis. Notably, AtRKD5, a RWP-RK domain-containing (RKD) transcription factor, binds to the 3' end of AtBBM and is identified as one of the inhibitory factors for AtBBM expression in the egg cell. In the atrkd5 mutant, we successfully achieved enhanced ectopic expression of AtBBM in egg cells, resulting in the generation of haploid offspring via parthenogenesis at a rate of 0.28%. Furthermore, by introducing chimeric Arabidopsis and rice BBM genes into the egg cell, we achieved a significant 4.6-fold enhancement in haploid induction through the atdmp8/9 mutant. These findings lay a strong foundation for further exploration of the BBM-mediated parthenogenesis mechanism and the improvement of haploid breeding efficiency mediated by the dmp8/9 mutant.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Partenogênese , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regiões Promotoras Genéticas/genética , Mutação/genéticaRESUMO
Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36.3 microduplications have rarely been reported. We report the two siblings of familial 1p36.3 microduplication, presenting with a severe global developmental delay, epilepsy, and a few dysmorphic features. They were referred to moderate-to-severe developmental delay (DD) and intellectual disability (ID). Both were considered eyelid myoclonus with absence of epilepsy (Jeavons syndrome). The EEG is characterized by widespread 2.5-3.5 Hz spikes and spike slow complex wave, eye closure sensitivity, and photosensitivity. The children has same dysmorphic features, including mild bitemporal narrowing and sloping forehead, sparse eyebrows, hypertelorism, ptosis, strabismus, infraorbital creases, wide nasal bridge with bulbous nasal tip, dystaxia, hallux valgus, and flat feet. Family exome sequencing revealed a maternally inherited 3.2-Mb microduplication of chromosomal band 1p36.3p36.2. However, DNA purified from blood samples of either parent did not find evidence for a microduplication of 1p36 in somatic tissue, indicating that such a mutation might be carried in the germline of the parents as gonadal mosaicism. No other family members of the affected siblings' parents were reported to be affected by the symptoms found.
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Epilepsia , Deficiência Intelectual , Criança , Humanos , Deficiência Intelectual/genética , Mutação , Epilepsia/genética , Deficiências do Desenvolvimento/genéticaRESUMO
BACKGROUND: Kinesin (KIN) as a motor protein is a versatile nano-machine and involved in diverse essential processes in plant growth and development. However, the kinesin gene family has not been identified in watermelon, a valued and nutritious fruit, and yet their functions have not been characterized. Especially, their involvement in early fruit development, which directly determines the size, shape, yield and quality of the watermelon fruit, remains unclear. RESULTS: In this study, we performed a whole-genome investigation and comprehensive analysis of kinesin genes in C. lanatus. In total, 48 kinesins were identified and categorized into 10 kinesin subfamilies groups based on phylogenetic analysis. Their uneven distribution on 11 chromosomes was revealed by distribution analysis. Conserved motif analysis showed that the ATP-binding motif of kinesins was conserved within all subfamilies, but not the microtubule-binding motif. 10 segmental duplication pairs genes were detected by the syntenic and phylogenetic approaches, which showed the expansion of the kinesin gene family in C. lanatus genome during evolution. Moreover, 5 ClKINs genes are specifically and abundantly expressed in early fruit developmental stages according to comprehensive expression profile analysis, implying their critical regulatory roles during early fruit development. Our data also demonstrated that the majority of kinesin genes were responsive to plant hormones, revealing their potential involvement in the signaling pathways of plant hormones. CONCLUSIONS: Kinesin gene family in watermelon was comprehensively analyzed in this study, which establishes a foundation for further functional investigation of C. lanatus kinesin genes and provides novel insights into their biological functions. In addition, these results also provide useful information for understanding the relationship between plant hormone and kinesin genes in C. lanatus.
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Citrullus/crescimento & desenvolvimento , Citrullus/genética , Citrullus/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/genética , Frutas/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Estudo de Associação Genômica AmplaRESUMO
Efficient genetic transformation has the potential to advance research and breeding in watermelon (Citrullus lanatus), but regeneration from tissue culture remains challenging. Previous work showed that expressing a fusion of two interacting transcription factors, GROWTH-REGULATING FACTOR4 (GRF4) and GRF-INTERACTING FACTOR1 (GIF1), improved regeneration in wheat (Triticum aestivum). By overexpressing a chimeric fusion of ClGRF4 and ClGIF1, we achieved highly efficient transformation in watermelon. Mutating the mi396 microRNA target site in ClGRF further boosted the transformation efficiency up to 67.27% in a genotype-independent manner. ClGRF4-GIF1 can also be combined with clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing tools to achieve highly efficient gene editing in watermelon, which we used to successfully create diploid seedless watermelon. This research thus puts forward a powerful transformation tool for future watermelon research and breeding.
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Citrullus , Edição de Genes , Sistemas CRISPR-Cas/genética , Citrullus/genética , Genótipo , Melhoramento Vegetal , Triticum/genéticaRESUMO
BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.
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Analgésicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Adulto , Analgésicos/efeitos adversos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The chemical investigation of the culture filtrate of endophyte Alternaria sp. W-1 associated with Laminaria japonica provided a new tricycloalternarene compound, 2H-(2E)-tricycloalternarene 12a (1), together with five known analogs: (2E)-tricycloalternarene 12a (2), tricycloalternarene 3a (3), tricycloalternarene F (4), 15-hydroxyl tricycloalternarene 5b (5), and ACTG-Toxin D (6). In vitro cytotoxicity against the human hepatocellular carcinoma cell line SMMC-7721 and the human gastric carcinoma cell line SGC-7901 was evaluated by the MTT method. Compounds 1, 3, and 4 inhibited the growth of SMMC-7721 cells with IC50 values of 49.7 ± 1.1, 45.8 ± 4.6, and 80.3 ± 3.8 µg/mL, respectively, while the IC50 value of the positive control cisplatin was 6.5 ± 0.5 µg/mL. Compounds 3 and 6 also showed moderate anti-proliferation activity against SGC-7901 cells with IC50 values of 53.2 ± 2.9 and 35.1 ± 0.8 µg/mL, respectively, while the IC50 value of cisplatin was 4.5 ± 0.6 µg/mL. Further studies revealed that the in vitro anticancer activity of compound 3 to SMMC-7721 cells was related to G1 phase cell cycle arrest and cell apoptosis, and the induced apoptosis was involved in both the mitochondrial pathway and the death receptor pathway. This is the first report on the anticancer mechanism of tricycloalternarene compounds.
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Alternaria/química , Antineoplásicos/farmacologia , Laminaria/microbiologia , Terpenos/farmacologia , Alternaria/isolamento & purificação , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Endófitos/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Terpenos/química , Proteína X Associada a bcl-2/metabolismoRESUMO
The suspensor is a temporary supporting structure of proembryos. It has been proposed that suspensor cells also possess embryogenic potential, which is suppressed by the embryo as an effect of the embryo-suspensor interaction. However, data to support this hypothesis are not yet available. In this report, using an in vivo living cell laser ablation technique, we show that Arabidopsis suspensor cells can develop into embryos after removing the embryo proper. The embryo proper plays a critical role in maintaining suspensor cell identity. However, this depends on the developmental stage; after the globular embryo stage, the suspensors no longer possess the potential to develop into embryos. We also reveal that hypophysis formation may be essential for embryo differentiation. Furthermore, we show that, after removing the embryo, auxin gradually accumulates in the top suspensor cell where cell division occurs to produce an embryo. Auxin redistribution likely reprograms the fate of the suspensor cell and triggers embryogenesis in suspensor cells. Thus, we provide direct evidence that the embryo suppresses the embryogenic potential of suspensor cells.
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Arabidopsis/citologia , Arabidopsis/embriologia , Sementes/citologia , Sementes/embriologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Diferenciação Celular , Divisão Celular , Células Cultivadas , Glucuronidase/genética , Glucuronidase/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Ácidos Indolacéticos/metabolismo , Microdissecção e Captura a Laser , Microscopia Confocal , Morfogênese , Plantas Geneticamente Modificadas , Sementes/genética , Fatores de Tempo , Técnicas de Cultura de Tecidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Wireless Power Transfer (WPT) technology is considered as a promising approach to make Wireless Rechargeable Sensor Network (WRSN) work perpetually. In WRSN, a vehicle exists, termed a mobile charger, which can move close to sensor nodes and charge them wirelessly. Due to the mobile charger's limited traveling distance and speed, not every node that needs to be charged may be serviced in time. Thus, in such scenario, how to make a route plan for the mobile charger to determine which nodes should be charged first is a critical issue related to the network's Quality of Service (QoS). In this paper, we propose a mobile charger's scheduling algorithm to mitigate the data loss of network by considering the node's criticality in connectivity and energy. First, we introduce a novel metric named criticality index to measure node's connectivity contribution, which is computed as a summation of node's neighbor dissimilarity. Furthermore, to reflect the node's charging demand, an indicator called energy criticality is adopted to weight the criticality index, which is a normalized ratio of the node's consumed energy to its total energy. Then, we formulate an optimization problem with the objective of maximizing total weighted criticality indexes of nodes to construct a charging tour, subject to the mobile charger's traveling distance constraint. Due to the NP-hardness of the problem, a heuristic algorithm is proposed to solve it. The heuristic algorithm includes three steps, which is spanning tree growing, tour construction and tour improvement. Finally, we compare the proposed algorithm to the state-of-art scheduling algorithms. The obtained results demonstrate that the proposed algorithm is a promising one.
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We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number. In these embryos, cell division cycle progression is delayed at the G2/M transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds, indicating that NtKRP and NtRPL17 function as partners in the same regulatory pathway during seed development and specifically regulate cell cycle progression to control embryo/seed size. This work reveals that NtRPL17, as a widely distributed ribosomal protein, plays a critical role in seed development and provides a new clue in the regulation of seed size. Confirmation of the interaction between NtKRP and NtRPL17 and their co-function in the control of the cell cycle also suggests that the mechanism might be conserved in both plants and animals.
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Cinesinas/genética , Nicotiana/crescimento & desenvolvimento , Nicotiana/genética , Proteínas de Plantas/genética , Proteínas Ribossômicas/genética , Cinesinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Ribossômicas/metabolismo , Plântula/genética , Plântula/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Nicotiana/metabolismoRESUMO
BACKGROUND: The aim of this study was to assess curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas between 3 and 5 cm in diameter and explore the optimal surgical indications. METHODS: A retrospective analysis was performed of those who underwent hysteroscopic or laparoscopic myomectomy from January 2008 to January 2013. The patients were divided into three subgroups according to the myomas diameter (namely, 30 mm ≤ myomas diameter <40 mm; 40 mm ≤ myomas diameter <50 mm; and myomas diameter ≥ 50 mm). Clinical data such as operation time, amount of bleeding, postoperative anal exsufflation time, hospital stay, and complications were collected. RESULTS: There was no significant difference regarding operation time and amount of bleeding in two groups. We found significant difference in hysteroscopic group (within-subgroup) difference regarding operation time and amount of bleeding, whereas no significant difference in the laparoscopic group, while significant differences between-subgroup differences regarding operation time. Complete removal of myoma was seen in all patients. CONCLUSIONS: Both techniques are feasible for type II submucous myomas. Laparoscopic operation has higher advantages in type II submucous myomas of greater than 4 cm in diameter whereas hysteroscopic operation has higher advantages in type II submucous myomas of lower than 4 cm in diameter.
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Histeroscopia , Laparoscopia , Leiomioma/cirurgia , Miomectomia Uterina/métodos , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Leiomioma/patologia , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/patologia , Adulto JovemRESUMO
A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 µg/ml, decreased the MIC80 of fluconazole from 128.0 µg/ml to 1.0-0.5 µg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.
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Amidas/química , Ácidos Cafeicos/química , Candida albicans/efeitos dos fármacos , Desenho de Fármacos , Fluconazol/química , Amidas/administração & dosagem , Ácidos Cafeicos/administração & dosagem , Candida albicans/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Farmacorresistência Fúngica/efeitos dos fármacos , Farmacorresistência Fúngica/fisiologia , Sinergismo Farmacológico , Fluconazol/administração & dosagem , Testes de Sensibilidade Microbiana/métodosRESUMO
Proline-rich proteins (PRPs) are known to play important roles in sexual plant reproduction. Most of the known proteins in the family were found in styles or pollen and modulate pollen tube growth. Here, we identified a novel member of the gene family, NtProRP1, which is preferentially expressed in tobacco pollen grains, pollen tubes and zygotes. NtProRP1 could be secreted into the extracellular space including the cell wall, and the predicted N-terminal signal peptide is crucial for its secretion. In NtProRP1-RNAi plants, pollen germination and pollen tube growth were significantly slower and showed zigzag or swell morphology in vitro. Early embryogenesis also exhibited aberrant development, indicative of its critical role in both pollen tube growth and early embryogenesis. Further investigation revealed that NtProRP1 plays a crucial role in osmotic stress response during pollen tube growth and is likely regulated by Tsi, a stress-responsive gene, suggesting that the regulatory mechanism is also involved in the stress response during sexual plant reproduction. These data provide evidence that NtProRP1 functions as a downstream factor of Tsi1 in the stress response and converges the stress signal into the modulation of pollen tube growth and early embryogenesis.
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Nicotiana/embriologia , Pressão Osmótica , Proteínas de Plantas/fisiologia , Tubo Polínico/crescimento & desenvolvimento , Sequência de Aminoácidos , Dados de Sequência Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reprodução , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína , Nicotiana/crescimento & desenvolvimento , Nicotiana/fisiologiaRESUMO
Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.
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Antifúngicos/farmacologia , Berberina/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Flufenazina/efeitos adversos , Proteínas Fúngicas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Extratos Vegetais/farmacologia , Candida albicans/metabolismo , Sinergismo Farmacológico , Flufenazina/uso terapêutico , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Proteínas de Membrana Transportadoras/genética , RNA Mensageiro/metabolismo , Ativação Transcricional/efeitos dos fármacos , Regulação para CimaRESUMO
Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
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Antifúngicos/farmacologia , Berberina/farmacologia , Candida albicans/efeitos dos fármacos , Fluconazol/farmacologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Isoquinolinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: The right posterior parietal cortex is the core brain region of emotional processing and executive control network in the human brain, and the function of the right posterior parietal cortex is decreased in patients with major depressive disorder. This study aims to preliminarily investigate whether the excitation of the right posterior parietal cortex by transcranial direct current stimulation (tDCS) could improve their clinical symptoms. METHODS: In this study, 12 patients with major depressive disorder were given tDCS treatment at Xuanwu Hospital of Capital Medical University and the First Hospital of Hebei Medical University. The stimulating electrode (anode) was placed on the patients' right parietal cortex, whereas the reference electrode (cathode) was placed on the patients' left mastoid. The stimulation intensity was set as 2.0 mA. The patients with depressive disorder were treated for 20 min at a time twice a day for 14 consecutive days. The severity of the clinical symptoms was evaluated using the Hamilton Depression Rating Scale-17 (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS) at before and right after treatment. RESULTS: The HDRS-17 scores of patients with depressive disorder decreased significantly following the tDCS treatment compared with those before treatment (p < .001). Further analysis revealed that the patients' anxiety/somatization, cognitive deficit, retardation, and sleep disorder scores all decreased significantly after the tDCS treatment (p < .05), although there was no significant change in their weight. Moreover, the patients' HARS scores decreased significantly after the tDCS treatment when compared with those before treatment (p < .01). CONCLUSION: The right parietal cortex may be another key stimulation targets to improving the efficacy of tDCS treatment to the patients with major depressive disorder.
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Transtorno Depressivo Maior , Lobo Parietal , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Lobo Parietal/fisiopatologia , Masculino , Feminino , Adulto , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/fisiopatologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Excessive secretion of human islet amyloid polypeptide (hIAPP) is an important pathological basis of diabetic encephalopathy (DE). In this study, we aimed to investigate the potential implications of hIAPP in DE pathogenesis. Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function. We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus. In vitro assays revealed that oligodendrocytes, compared with neurons, were more prone to acidosis under exogenous hIAPP stimulation. Moreover, western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter (MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70. Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2 (YIPF2, which modulates the transfer of CD147 to the cell membrane) as a significant target. Furthermore, YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice. These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding, potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.
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Cytosine and adenosine base editors (CBEs and ABEs) are novel genome-editing tools that have been widely utilized in molecular breeding to precisely modify single-nucleotide polymorphisms (SNPs) critical for plant agronomic traits and species evolution. However, conventional BE editors are limited to achieve C-to-T and A-to-G substitutions, respectively. To enhance the applicability of base editing technology in watermelon, we developed an efficient CGBE editor (SCGBE2.0) by removing the uracil glycosylase inhibitor (UGI) unit from the commonly used hA3A-CBE and incorporating the uracil-DNA glycosylase (UNG) component. Seven specific guide RNAs (sgRNAs) targeting five watermelon genes were designed to assess the editing efficiency of SCGBE. The results obtained from stably transformed watermelon plants demonstrated that SCGBE2.0 could efficiently induce C-to-G mutations at positions C5-C9 in 43.2% transgenic plants (with a maximum base conversion efficiency of 46.1%) and C-to-A mutation at position C4 in 23.5% transgenic plants (with a maximum base conversion efficiency of 45.9%). These findings highlight the capability of our integrated SCGBE2.0 editor to achieve C-to-G/A mutations in a site-preferred manner, thus providing an efficient base editing tool for precise base modification and site-directed saturated mutagenesis in watermelon.
RESUMO
BACKGROUND: Cerebral microbleeds (CMBs) are common in acute ischemic stroke (AIS) patients. The presence of CMBs increases the risk of hemorrhagic transformation in AIS patients, and it is also closely associated with cognitive decline and even dementia. At present, there exist different opinions on the independent risk factors for CMBs, and there is no consensus on whether there are gender differences in -post-stroke CMB. Therefore, this study sought to investigate gender heterogeneity in the influencing factors for CMBs by studying male and female AIS patients. METHODS: This was a China-based, Single-center, retrospective review of data from 482 AIS inpatients at the Neurology Department of Hebei General Hospital (NCT05882123). Both demographic and clinical data were collected from the study subjects. Different head magnetic resonance imaging sequences were used to assess the subjects' CMBs, white matter lesions, and old lacunar infarcts (LI). Various statistical methods, including the t-test, χ2 test, and logistic regression, were used to analyze the gender heterogeneity of the influencing factors for CMBs in AIS patients. RESULTS: When compared with the male AIS patients, the female AIS patients were older and had higher total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, ApoA, ApoB, and fibrinogen levels. The female AIS patients also had higher National Institute of Health Stroke Scale scores and hypertension disease composition ratios. By contrast, the proportions of female AIS patients with a history of smoking and a history of alcohol consumption were both lower than the corresponding proportions of male AIS patients. These differences were all statistically significant (p < .05). There were no statistically significant differences in the incidence and severity of CMBs between the male and female AIS patients (χ2 ï¼ 0.851, 3.092, p > .05). The univariate and multivariate stepwise logistic regression analyses confirmed that age (OR = 1.074, 95% CI: 1.013-1.139, p = .016) and old LI (OR = 4.295, 95% CI: 1.062-17.375, p = .041) were independent risk factors for comorbid CMBs in the female AIS patients, while blood glucose (OR = 0.692, 95% CI: 0.494-0.968, p = .031) was an independent protective factor for comorbid CMBs in the female AIS patients. However, these factors were not found to be independent risk or protective factors for comorbid CMBs in male AIS patients. CONCLUSION: There are gender differences in the influencing factors for CMBs in AIS patients. Age, old LIs, and blood glucose are independent risk or protective factors for comorbid CMBs in female AIS patients, although they are not associated with the risk of developing CMBs in male AIS patients.